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Fest SN, Farland LV, Doody DR, Eliassen AH, Rosner BA, Fung TT, Hankinson SE, Kensler TW, Willett WC, Harris HR. Hormone-associated dietary patterns and premenopausal breast cancer risk. Breast Cancer Res Treat 2025; 212:23-35. [PMID: 40159249 DOI: 10.1007/s10549-025-07689-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/15/2025] [Indexed: 04/02/2025]
Abstract
PURPOSE Circulating levels of sex steroid hormones have previously been associated with premenopausal breast cancer risk. Few studies have considered the association between dietary patterns and premenopausal hormone levels. Our objective was to derive dietary patterns associated with premenopausal hormone levels and investigate the association between pattern scores and premenopausal breast cancer risk. METHODS Using reduced rank regression among a subset of participants from the Nurses' Health Study II (NHSII) (n = 8,962), we identified dietary patterns correlated with premenopausal levels of five sex steroid hormones measured in the follicular and luteal phases. Then, in the full NHSII cohort (n = 90,341), we used Cox proportional hazards models to calculate hazard ratios (HRs) for breast cancer risk associated with each dietary pattern score. RESULTS Dietary patterns were identified for luteal estradiol, luteal free estradiol, follicular estrone, luteal estrone, and free testosterone. However, these patterns explained a low percent variation in individual hormone levels, ranging from 2.5-4.1%. During 24 years of follow-up, 1,956 premenopausal breast cancer cases were ascertained. Dietary patterns associated with luteal free estradiol (HR for fifth versus first quintile = 1.29; 95% CI = 1.11-1.49; Ptrend < 0.01) and follicular estrone (HR for fifth versus first quintile = 1.28; 95% CI = 1.10-1.49; Ptrend < 0.01) were positively associated with premenopausal breast cancer risk. CONCLUSION Our findings indicate that while some dietary factors may marginally influence premenopausal hormone levels, the relation between sex steroid hormones and premenopausal breast cancer risk is likely not driven by diet. Future studies should consider other mechanisms through which diet may impact breast cancer risk, including inflammatory processes.
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Affiliation(s)
- Sable N Fest
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Avenue North, Seattle, WA, USA
| | - Leslie V Farland
- Department of Epidemiology & Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
- Department of Obstetrics and Gynecology, College of Medicine - Tucson, University of Arizona, Tucson, AZ, USA
| | - David R Doody
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Avenue North, Seattle, WA, USA
| | - A Heather Eliassen
- Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Bernard A Rosner
- Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Teresa T Fung
- Department of Nutrition, Simmons University, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Susan E Hankinson
- Department of Biostatistics & Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA
| | - Thomas W Kensler
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Avenue North, Seattle, WA, USA
| | - Walter C Willett
- Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Holly R Harris
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Avenue North, Seattle, WA, USA.
- Department of Epidemiology, University of Washington, Seattle, WA, USA.
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Aboumrad M, Joshu C, Visvanathan K. Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study. J Natl Cancer Inst 2025; 117:653-664. [PMID: 39531324 PMCID: PMC11972680 DOI: 10.1093/jnci/djae287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 10/19/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Establishing whether women with major depressive disorder who develop breast cancer have poor outcomes is key to optimizing care for this population. To this end, we examined associations between major depressive disorder and breast cancer recurrence and mortality. METHODS Using medical record data from the US Department of Veterans Affairs health-care system, we established a retrospective cohort of women with local or regional stage invasive breast cancer between 2010 and 2019 and followed them through 2022. We used a 2-year window to identify women diagnosed with major depressive disorder before breast cancer diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between major depressive disorder and breast cancer recurrence and mortality while accounting for competing risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. RESULTS We identified 6051 women with breast cancer, of whom 1754 (29%) had major depressive disorder. The mean (SD) age at breast cancer diagnosis was 57 (11) years. In multivariable analyses, women with major depressive disorder had a 37% (hazard ratio = 1.37, 95% CI = 1.19 to 1.57) higher risk of recurrence and a 30% (hazard ratio = 1.30, 95% CI = 1.02 to 1.64) higher risk of breast cancer mortality. The association between major depressive disorder and recurrence was stronger among women with estrogen receptor-positive breast cancer. In secondary analyses, there were statistically significant interactions between major depressive disorder and multiple exposures with respect to recurrence, including current smoking, substance abuse, and nonreceipt of screening mammography. CONCLUSIONS Women with major depressive disorder had inferior breast cancer outcomes compared with women without a history of major depressive disorder. Research is needed to investigate underlying mechanisms linking depression to breast cancer progression and evaluate interventions to improve outcomes in this high-risk population.
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Affiliation(s)
- Maya Aboumrad
- White River Junction VA Medical Center, White River Junction, VT 05009, United States
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States
| | - Corinne Joshu
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21205, United States
| | - Kala Visvanathan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21205, United States
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García-Sancha N, Corchado-Cobos R, Pérez-Losada J. Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies. Int J Mol Sci 2025; 26:2993. [PMID: 40243654 PMCID: PMC11988588 DOI: 10.3390/ijms26072993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/23/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
Breast cancer is the most common malignancy among women globally, with incidence rates continuing to rise. A comprehensive understanding of its risk factors and the underlying biological mechanisms that drive tumor initiation is essential for developing effective prevention strategies. This review examines key non-modifiable risk factors, such as genetic predisposition, demographic characteristics, family history, mammographic density, and reproductive milestones, as well as modifiable risk factors like exogenous hormone exposure, obesity, diet, and physical inactivity. Importantly, reproductive history plays a dual role, providing long-term protection while temporarily increasing breast cancer risk shortly after pregnancy. Current chemoprevention strategies primarily depend on selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, which have demonstrated efficacy in reducing the incidence of estrogen receptor-positive breast cancer but remain underutilized due to adverse effects. Emerging approaches such as aromatase inhibitors, RANKL inhibitors, progesterone antagonists, PI3K inhibitors, and immunoprevention strategies show promise for expanding preventive options. Understanding the interactions between risk factors, hormonal influences, and tumorigenesis is critical for optimizing breast cancer prevention and advancing safer, more targeted chemopreventive interventions.
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Affiliation(s)
- Natalia García-Sancha
- Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain; (R.C.-C.); (J.P.-L.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Roberto Corchado-Cobos
- Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain; (R.C.-C.); (J.P.-L.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Jesús Pérez-Losada
- Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain; (R.C.-C.); (J.P.-L.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
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Ren F, Yang C, Feng K, Shang Q, Liu J, Kang X, Wang X, Wang X. An exploration of causal relationships between nine neurological diseases and the risk of breast cancer: a Mendelian randomization study. Aging (Albany NY) 2024; 16:7101-7118. [PMID: 38663930 PMCID: PMC11087125 DOI: 10.18632/aging.205745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 03/18/2024] [Indexed: 05/08/2024]
Abstract
BACKGROUND Some preceding researches have observed that certain neurological disorders, such as Alzheimer's disease and multiple sclerosis, may affect breast cancer risk. However, whether there are causal relationships between these neurological conditions and breast cancer is inconclusive. This study was designed to explore whether neurological disorders affected the risks of breast cancer overall and of the two subtypes (ER+ and ER-). METHODS In the course of this study, genome-wide association study (GWAS) data for nine neurological diseases (Alzheimer's disease, multiple sclerosis, Parkinson's disease, myasthenia gravis, generalized epilepsy, intracerebral haemorrhage, cerebral atherosclerosis, brain glioblastoma, and benign meningeal tumour) were collected from the Complex Trait Genetics lab and the MRC Integrative Epidemiology Unit, and single-nucleotide polymorphisms (SNPs) extensively associated with these neurological ailments had been recognized as instrumental variables (IVs). GWAS data on breast cancer were collected from the Breast Cancer Association Consortium (BCAC). Two-sample Mendelian randomization (MR) analyses as well as multivariable MR analyses were performed to determine whether these SNPs contributed to breast cancer risk. Additionally, the accuracy of the results was evaluated using the false discovery rate (FDR) multiple correction method. Both heterogeneity and pleiotropy were evaluated by analyzing sensitivities. RESULTS According to the results of two-sample MR analyses, Alzheimer's disease significantly reduced the risks of overall (OR 0.925, 95% CI [0.871-0.982], P = 0.011) and ER+ (OR 0.912, 95% CI [0.853-0.975], P = 0.007) breast cancer, but there was a negative result in ER- breast cancer. However, after multiple FDR corrections, the effect of Alzheimer's disease on overall breast cancer was not statistically significant. In contrast, multiple sclerosis significantly increased ER+ breast cancer risk (OR 1.007, 95% CI [1.003-1.011], P = 0.001). In addition, the multivariable MR analyses showed that Alzheimer's disease significantly reduced the risk of ER+ breast cancer (IVW: OR 0.929, 95% CI [0.864-0.999], P=0.047; MR-Egger: OR 0.916, 95% CI [0.846-0.992], P=0.031); however, multiple sclerosis significantly increased the risk of ER+ breast cancer (IVW: OR 1.008, 95% CI [1.003-1.012], P=4.35×10-4; MR-Egger: OR 1.008, 95% CI [1.003-1.012], P=5.96×10-4). There were no significant associations between the remainder of the neurological diseases and breast cancer. CONCLUSIONS This study found the trends towards a decreased risk of ER+ breast cancer in patients with Alzheimer's disease and an increased risk in patients with multiple sclerosis. However, due to the limitations of Mendelian randomization, we cannot determine whether there are definite causal relationships between neurological diseases and breast cancer risk. For conclusive evidences, more prospective randomized controlled trials will be needed in the future.
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Affiliation(s)
- Fei Ren
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chenxuan Yang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kexin Feng
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qingyao Shang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiaxiang Liu
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiyu Kang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xin Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiang Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Kwan ML, Valice E, Ergas IJ, Roh JM, Caan BJ, Cespedes Feliciano EM, Kolevska T, Hartman TJ, Quesenberry CP, Ambrosone CB, Kushi LH. Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study. Cancer 2023; 129:3938-3951. [PMID: 37555890 PMCID: PMC10840903 DOI: 10.1002/cncr.34972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 06/24/2023] [Accepted: 06/28/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND The impact of alcohol consumption on breast cancer (BC) prognosis remains unclear. METHODS The authors examined short-term alcohol intake in relation to recurrence and mortality in 3659 women who were diagnosed with stage I-IV BC from 2003 to 2013 in the Pathways Study. Alcohol drinking in the past 6 months was assessed at cohort entry (mean, 2 months postdiagnosis) and 6 months later using a food-frequency questionnaire. Study end points were recurrence and death from BC, cardiovascular disease, and all causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS Over an average follow-up of 11.2 years, 524 recurrences and 834 deaths (369 BC-specific and 314 cardiovascular disease-specific) occurred. Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers. Overall, alcohol consumption was not associated with recurrence or mortality. However, women with higher body mass index (BMI ≥ 30 kg/m2 ) had lower risk of overall mortality with increasing alcohol consumption for occasional drinking (HR, 0.71; 95% CI, 0.54-0.94) and regular drinking (HR, 0.77; 95% CI, 0.56-1.08) around the time of diagnosis, along with 6 months later, in a dose-response manner (p < .05). Women with lower BMI (<30 kg/m2 ) were not at higher risk of mortality but were at possibly higher, yet nonsignificant, risk of recurrence for occasional drinking (HR, 1.29; 95% CI, 0.97-1.71) and regular drinking (HR, 1.19; 95% CI, 0.88-1.62). CONCLUSIONS Alcohol drinking around the time of and up to 6 months after BC diagnosis was associated with lower risk of all-cause mortality in obese women. A possible higher risk of recurrence was observed in nonobese women.
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Affiliation(s)
- Marilyn L Kwan
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Emily Valice
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Isaac J Ergas
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Janise M Roh
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Bette J Caan
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | | | - Tatjana Kolevska
- Department of Oncology, Kaiser Permanente Vallejo Medical Center, Vallejo, California, USA
| | - Terryl J Hartman
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Charles P Quesenberry
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Christine B Ambrosone
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Lawrence H Kushi
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
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Chen X, Hu G. Correlation study of malignant lymphoma and breast Cancer in different gender European populations: mendelian randomization analysis. BMC Genom Data 2023; 24:59. [PMID: 37814219 PMCID: PMC10561426 DOI: 10.1186/s12863-023-01162-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 09/29/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND Previous research has already indicated an elevated risk of breast cancer (BC) among survivors of malignant lymphoma, but the underlying reasons remain unknown. Our objective is to elucidate the causal relationship between malignant lymphoma and BC through Mendelian randomization (MR). Genome-wide association studies (GWAS) data from 181,125 Hodgkin lymphoma (HL) patients and 181,289 non-Hodgkin lymphoma (NHL) patients from the FinnGen Consortium were utilized as exposure. We selected single nucleotide polymorphisms (SNPs) strongly associated with the exposure as instrumental variables to investigate their relationship with BC in a cohort of 107,722 participants. Subsequently, we obtained data from the UK Biobank containing gender-stratified information on HL, NHL, and BC. We validated the findings from our analysis and explored the impact of gender. The Inverse-Variance Weighted (IVW) method served as the primary reference for the two-sample MR, accompanied by tests for heterogeneity and pleiotropy. RESULTS The analysis results from the FinnGen consortium indicate that there is no causal relationship between HL and NHL with BC. HL (OR = 1.01, 95% CI = 0.98-1.04, p = 0.29), NHL (OR = 1.01, 95% CI = 0.96-1.05, p = 0.64). When utilizing GWAS data from the UK Biobank that includes different gender cohorts, the lack of association between HL, NHL, and BC remains consistent. HL (OR = 1.08, 95% CI = 0.74-1.56, p = 0.69), HL-Female (OR = 0.84, 95% CI = 0.59-1.19, p = 0.33), NHL (OR = 0.89, 95% CI = 0.66-1.19, p = 0.44), and NHL-Female (OR = 0.81, 95% CI = 0.58-1.11, p = 0.18). CONCLUSIONS The two-sample MR analysis indicates that there is no significant causal relationship between malignant lymphoma (HL and NHL) and BC. The association between malignant lymphoma and breast cancer requires further in-depth research and exploration.
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Affiliation(s)
- Xiong Chen
- Department of General Surgery, Affiliated Changsha Hospital of Hunan Normal University, Changsha, 410000 China
| | - GuoHuang Hu
- Department of General Surgery, Affiliated Changsha Hospital of Hunan Normal University, Changsha, 410000 China
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Driutti M, Dal Maso L, Toffolutti F, Valdi G, Bidoli E, Giudici F, Parpinel M, Serraino D. Breast cancer deaths attributable to alcohol consumption: Italy, 2015-2019. Breast 2023; 71:96-98. [PMID: 37562109 PMCID: PMC10432776 DOI: 10.1016/j.breast.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/28/2023] [Accepted: 08/05/2023] [Indexed: 08/12/2023] Open
Abstract
A study was conducted to assess the fraction of female breast cancer (BC) deaths attributable to alcohol consumption in Italy. National mortality data for the period 2015-2019 were used along with national estimates of women from the general population exposed to moderate (11-20 gr/day) or heavy (>20 gr/day) alcohol consumption. From 2015 to 2019, 2918 (4.6%) out of 63,428 BC| deaths were attributable to alcohol consumption, including 1269 deaths (2.0%) caused by moderate consumption. Study findings could help stakeholders to prioritize programs aimed at reducing alcohol consumption, and to improve ways to effectively communicate alcohol-related health risks, including moderate consumption.
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Affiliation(s)
- Marco Driutti
- Dipartimento di Area Medica, Università degli Studi di Udine, Via Colugna 50, 33100, Udine, Italy.
| | - Luigino Dal Maso
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini, 2 - 33081, Aviano, PN, Italy.
| | - Federica Toffolutti
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini, 2 - 33081, Aviano, PN, Italy.
| | - Giulia Valdi
- Dipartimento di Area Medica, Università degli Studi di Udine, Via Colugna 50, 33100, Udine, Italy.
| | - Ettore Bidoli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini, 2 - 33081, Aviano, PN, Italy.
| | - Fabiola Giudici
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini, 2 - 33081, Aviano, PN, Italy.
| | - Maria Parpinel
- Dipartimento di Area Medica, Università degli Studi di Udine, Via Colugna 50, 33100, Udine, Italy.
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via F. Gallini, 2 - 33081, Aviano, PN, Italy.
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Junkka SS, Ohlsson B. Associations and gastrointestinal symptoms in women with endometriosis in comparison to women with irritable bowel syndrome: a study based on a population cohort. BMC Gastroenterol 2023; 23:228. [PMID: 37400789 DOI: 10.1186/s12876-023-02861-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 06/21/2023] [Indexed: 07/05/2023] Open
Abstract
BACKGROUND Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. METHOD The study cohort included women from the Malmö Offspring Study with information about endometriosis and IBS diagnoses from the National Board of Health and Welfare. The participants answered a questionnaire about lifestyle habits, medical and drug history, and self-reported IBS. The visual analog scale for IBS was used to estimate gastrointestinal symptoms the past 2 weeks. Endometriosis diagnosis and self-reported IBS were used as dependent variables to study associations with age, body mass index (BMI), education, occupation, marital status, smoking, alcohol habits, and physical activity using logistic regression. Mann-Whitney U Test or Kruskal-Wallis tests were used to calculate the differences in symptoms between groups. RESULTS Of the 2,200 women with information from medical records, 72 participants had endometriosis; 21 (29.2%) of these had self-reported IBS. Of the 1,915 participants who had answered the questionnaire, 436 (22.8%) had self-reported IBS. Endometriosis was associated with IBS (OR:1.86; 95%CI:1.06-3.26; p = 0.029), as well as with age 50-59 years (OR:6.92; 95%CI:1.97-24.32; p = 0.003), age ≥ 60 years (OR:6.27; 95%CI:1.56-25.17; p = 0.010), sick leave (OR:2.43; 95%CI:1.08-5.48; p = 0.033), and former smoking (OR:3.02; 95%CI:1.19-7.68; p = 0.020). There was an inverse association with BMI (OR:0.36; 95%CI:0.14-4.91; p = 0.031). IBS was associated with endometriosis (OR:1.77; 95%CI:1.02-3.07; p = 0.041) and sick leave (OR:1.77; 95%CI:1.14-2.73; p = 0.010), with a tendency to association with smoking (OR:1.30; 95%CI:0.98-1.72; p = 0.071). When excluding participants using drugs associated with IBS, the condition was associated with current smoking (OR:1.39; 95%CI:1.03-1.89; p = 0.033) and inversely with age 50-59 years (OR:0.58; 95%CI:0.38-0.90; p = 0.015). There were differences in the gastrointestinal symptoms between IBS and healthy participants, but not between endometriosis and IBS or healthy participants. CONCLUSION There were associations between endometriosis and IBS, without differences in gastrointestinal symptoms. Both IBS and endometriosis were associated with smoking and sick leave. Whether the associations reflect causality or depend on common risk factors and pathogenesis remains to be determined.
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Affiliation(s)
| | - Bodil Ohlsson
- Department of Clinical Science, Lund University, Malmö, Sweden.
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
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Young KL, Olshan AF, Lunetta K, Graff M, Williams LA, Yao S, Zirpoli GR, Troester M, Palmer JR. Influence of alcohol consumption and alcohol metabolism variants on breast cancer risk among Black women: results from the AMBER consortium. Breast Cancer Res 2023; 25:66. [PMID: 37308906 PMCID: PMC10259046 DOI: 10.1186/s13058-023-01660-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 05/21/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Moderate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, with little information available among women of African ancestry. METHODS Our analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, and ALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (≥ 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer. RESULTS Among current drinkers, 21% of cases and 14% of controls reported consuming ≥ 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C in CYP2E1 with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (≥ 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24, pjoint = 3.74 × 10-6). In addition, there was a statistically significant interaction of rs3858704-A in ALDH2 with consumption of ≥ 7 drinks/week on odds of triple negative breast cancer (≥ 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57, pint = 8.97 × 10-5). CONCLUSIONS There is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C in CYP2E1 and odds of ER- and triple negative breast cancer. Replication of these findings is warranted.
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Affiliation(s)
- Kristin L Young
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA.
| | - Andrew F Olshan
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA
| | - Kathryn Lunetta
- Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA
| | - Mariaelisa Graff
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA
| | - Lindsay A Williams
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA
- Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55455, USA
| | - Song Yao
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA
| | - Gary R Zirpoli
- Slone Epidemiology Center, Boston University, Boston, MA, 02215, USA
| | - Melissa Troester
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA
| | - Julie R Palmer
- Slone Epidemiology Center, Boston University, Boston, MA, 02215, USA
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10
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Mubarik S, Wang F, Nadeem AA, Fawad M, Yu C. Breast cancer epidemiology and sociodemographic differences in BRICS-plus countries from 1990 to 2019: An age period cohort analysis. SSM Popul Health 2023; 22:101418. [PMID: 37215157 PMCID: PMC10193025 DOI: 10.1016/j.ssmph.2023.101418] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 04/18/2023] [Accepted: 04/29/2023] [Indexed: 05/24/2023] Open
Abstract
Background Breast cancer (BC) is a major health concern in the BRICS-plus, a group of developing nations consisting of Brazil, Russia, India, China, South Africa, and 30 other Asian countries, with nearly half of the world's population. This study aims to identify potential risk factors contributing to the burden of BC by assessing its epidemiological and socio-demographic changes. Methods Data on BC outcomes were obtained from the 2019 Global Burden of Disease Survey. The age-period-cohort (APC) modeling technique was used to evaluate the nonlinear impacts of age, cohort, and period on BC outcomes and reported risk attributable mortality and disability adjusted life years (DALYs) rate changes between 1990 and 2019. Results In 2019, there were 0.90 million female BC cases and 0.35 million deaths in the BRICS-plus region, with China and India having the largest proportion of incident cases and deaths, followed by Pakistan. Lesotho experienced the highest annualized rates of change (AROC: 2.61%; 95%UI: 1.99-2.99) in the past three decades. Birth cohorts' impact on BC varies greatly between the BRICS-plus nations, with Pakistan suffering the largest risk increase in the most recent cohort. High body mass index (BMI), high fasting plasma glucose (FPG), and a diet high in red meat contributed to the highest death and DALYs rates in most BRICS-plus nations in 2019, and there was a strong negative link between SDI and death and DALYs rate. Conclusions The study found that the burden of BC varies significantly between BRICS-plus regions. Thus, BRICS-plus nations should prioritise BC prevention, raise public awareness, and implement screening efficiency measures to reduce the burden of BC in the future, as well as strengthen public health policies and initiatives for important populations based on their characteristics and adaptability.
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Affiliation(s)
- Sumaira Mubarik
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, 430071, China
| | - Fang Wang
- Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Adeel Ahmad Nadeem
- State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, Wuhan, 430072, China
| | - Muhammad Fawad
- School of Public Health and Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
| | - Chuanhua Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, 430071, China
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11
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Yaghjyan L, Heng YJ, Baker GM, Rosner BA, Tamimi RM. Associations of alcohol consumption with breast tissue composition. Breast Cancer Res 2023; 25:33. [PMID: 36998083 PMCID: PMC10061845 DOI: 10.1186/s13058-023-01638-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 03/13/2023] [Indexed: 04/01/2023] Open
Abstract
BACKGROUND We investigated the associations of alcohol with percentage of epithelium, stroma, fibroglandular tissue (epithelium + stroma), and fat in benign breast biopsy samples. METHODS We included 857 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII cohorts. Percentage of each tissue was measured on whole slide images using a deep-learning algorithm and then log-transformed. Alcohol consumption (recent and cumulative average) was assessed with semi-quantitative food frequency questionnaires. Regression estimates were adjusted for known breast cancer risk factors. All tests were 2-sided. RESULTS Alcohol was inversely associated with % of stroma and fibroglandular tissue (recent ≥ 22 g/day vs. none: stroma: β = - 0.08, 95% Confidence Interval [CI] - 0.13; - 0.03; fibroglandular: β = - 0.08, 95% CI - 0.13; - 0.04; cumulative ≥ 22 g/day vs. none: stroma: β = - 0.08, 95% CI - 0.13; - 0.02; fibroglandular: β = - 0.09, 95% CI - 0.14; - 0.04) and positively associated with fat % (recent ≥ 22 g/day vs. none: β = 0.30, 95% CI 0.03; 0.57; cumulative ≥ 22 g/day vs. none: β = 0.32, 95% CI 0.04; 0.61). In stratified analysis, alcohol consumption was not associated with tissue measures in premenopausal women. In postmenopausal women, cumulative alcohol use was inversely associated with % of stroma and fibroglandular tissue and positively associated with fat % (≥ 22 g/day vs. none: stroma: β = - 0.16, 95% CI - 0.28; - 0.07; fibroglandular: β = - 0.18, 95% CI - 0.28; - 0.07; fat: β = 0.61, 95% CI 0.01; 1.22), with similar results for recent alcohol use. CONCLUSION Our findings suggest that alcohol consumption is associated with smaller % of stroma and fibroglandular tissue and a greater % of fat in postmenopausal women. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.
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Affiliation(s)
- Lusine Yaghjyan
- Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, 2004 Mowry Rd., Gainesville, FL, 32610, USA.
| | - Yujing J Heng
- Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Gabrielle M Baker
- Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Bernard A Rosner
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
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12
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Doyle A, O'Dwyer C, Mongan D, Millar SR, Galvin B. Factors associated with public awareness of the relationship between alcohol use and breast cancer risk. BMC Public Health 2023; 23:577. [PMID: 36978036 PMCID: PMC10044731 DOI: 10.1186/s12889-023-15455-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/16/2023] [Indexed: 03/30/2023] Open
Abstract
BACKGROUND Public awareness of the carcinogenic effects of alcohol is low, particularly the association between alcohol use and the risk of developing breast cancer. Breast cancer is the third most common cancer in Ireland and alcohol use remains high. This study examined factors related to awareness of the association between alcohol use and breast cancer risk. METHODS Using data from Wave 2 of the national Healthy Ireland Survey, a representative sample of 7,498 Irish adults aged 15 + years, descriptive and logistic regression analyses were conducted to investigate relationships between demographic characteristics, type of drinker and awareness of breast cancer risk. RESULTS A low level of awareness of the risk of alcohol use (drinking more than the recommended low-risk limit) associated with breast cancer was found, with just 21% of respondents correctly identifying the relationship. Multivariable regression analyses found that factors most strongly associated with awareness were sex (female), middle age (45-54 years) and higher educational levels. CONCLUSION As breast cancer is a prevalent disease among women in Ireland, it is essential that the public, in particular women who drink, are made aware of this association. Public health messages that highlight the health risks associated with alcohol use, and which target individuals with lower educational levels, are warranted.
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Affiliation(s)
- Anne Doyle
- Health Research Board, Grattan House 67-72 Lower Mount Street, Dublin, Ireland.
| | - Claire O'Dwyer
- Health Research Board, Grattan House 67-72 Lower Mount Street, Dublin, Ireland
| | - Deirdre Mongan
- Health Research Board, Grattan House 67-72 Lower Mount Street, Dublin, Ireland
| | - Seán R Millar
- Health Research Board, Grattan House 67-72 Lower Mount Street, Dublin, Ireland
- School of Public Health, University College Cork, 4th Floor, Western Gateway Building, Cork, Ireland
| | - Brian Galvin
- Health Research Board, Grattan House 67-72 Lower Mount Street, Dublin, Ireland
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13
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Liu S, Feng S, Du F, Zhang K, Shen Y. Association of smoking, alcohol, and coffee consumption with the risk of ovarian cancer and prognosis: a mendelian randomization study. BMC Cancer 2023; 23:256. [PMID: 36941558 PMCID: PMC10026459 DOI: 10.1186/s12885-023-10737-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 03/14/2023] [Indexed: 03/22/2023] Open
Abstract
OBJECTIVE Currently, the association between smoking, alcohol, and coffee intake and the risk of ovarian cancer (OC) remains conflicting. In this study, we used a two-sample mendelian randomization (MR) method to evaluate the association of smoking, drinking and coffee consumption with the risk of OC and prognosis. METHODS Five risk factors related to lifestyles (cigarettes per day, smoking initiation, smoking cessation, alcohol consumption and coffee consumption) were chosen from the Genome-Wide Association Study, and 28, 105, 10, 36 and 36 single-nucleotide polymorphisms (SNPs) were obtained as instrumental variables (IVs). Outcome variables were achieved from the Ovarian Cancer Association Consortium. Inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS The two-sample MR analysis supported the causal association of genetically predicted smoking initiation (OR: 1.15 per SD, 95%CI: 1.02-1.29, P = 0.027) and coffee consumption (OR: 1.40 per 50% increase, 95%CI: 1.02-1.93, P = 0.040) with the risk of OC, but not cigarettes per day, smoking cessation, and alcohol consumption. Subgroup analysis based on histological subtypes revealed a positive genetical predictive association between coffee consumption and endometrioid OC (OR: 3.01, 95%CI: 1.50-6.04, P = 0.002). Several smoking initiation-related SNPs (rs7585579, rs7929518, rs2378662, rs10001365, rs11078713, rs7929518, and rs62098013), and coffee consumption-related SNPs (rs4410790, and rs1057868) were all associated with overall survival and cancer-specific survival in OC. CONCLUSION Our findings provide the evidence for a favorable causal association of genetically predicted smoking initiation and coffee consumption with OC risk, and coffee consumption is linked to a greater risk of endometrioid OC.
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Affiliation(s)
- Sicong Liu
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Songwei Feng
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Furong Du
- State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, Jiangsu, 210042, China
| | - Ke Zhang
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Yang Shen
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
- Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
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14
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Lv L, Zhao B, Kang J, Li S, Wu H. Trend of disease burden and risk factors of breast cancer in developing countries and territories, from 1990 to 2019: Results from the Global Burden of Disease Study 2019. Front Public Health 2023; 10:1078191. [PMID: 36726635 PMCID: PMC9884979 DOI: 10.3389/fpubh.2022.1078191] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/20/2022] [Indexed: 01/18/2023] Open
Abstract
Background The incidence, mortality, burden of disability-adjusted life years (DALYs), and attributable risk factors of breast cancer vary significantly by country or region, particularly between developing and developed countries. This study aimed to analyze breast cancer development trends in developing countries based on the influence of the different sociodemographic indices (SDIs) and World Bank (WB) income-level disease data from 1990 to 2019. Methods Data on the annual incidence, mortality, DALY, years of life lost (YLL) prematurely, years lived with disability (YLD), and age-standardized rate (ASR) of breast cancer from 1990 to 2019 in different countries and territories were obtained from the 2019 Global Burden of Disease (GBD) Study. A comparative risk assessment (CRA) framework was used to analyze the general risk factors. Results The global age-standardized incidence rate (ASIR) gradually increased from 21.44 per 100,000 population in 1990 to 24.17 per 100,000 population in 2019. It rose precipitously to 2.91- and 2.49-fold, respectively, for countries with middle SDIs and low-middle SDIs. The ASIR of breast cancer was increasing in the lower-middle-income levels in WB, with an estimated annual percentage change (EAPC) of 0.29 [95% uncertainty interval (UI): 0.20-0.37] and reduced income (EAPC of 0.59 [95% UI: 0.53-0.65]). The Solomon Islands and the United Arab Emirates observed the most significant increase in the magnitude of deaths from breast cancer cases. Compared to the death cases of 1990, percentage changes increased separately by 1,169 and 851%. Compared to developed areas, breast cancer-related deaths increased rapidly in developing regions, especially among the middle-aged and elderly groups. Meanwhile, the long-term burden of breast cancer was ever expanding. Of all the GBD regions, Oceania had the youngest age distribution. The deaths in the young and middle-aged groups accounted for 69% in 1990 and 72% in 2019. Percentage changes in deaths from the seven risk factors in low- to middle-SDI regions increased significantly over time across all age groups. However, a diet with high red meat and high body mass index (BMI) accounted for the most considerable increase in the magnitude. Conclusion Public health policy regarding breast cancer is fundamental in low- and medium-income countries. The development and adoption of cost-effective screening and therapeutic solutions, the mitigation of risk factors, and the establishment of a cancer infrastructure are essential.
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Affiliation(s)
- Linlin Lv
- Key Laboratory of Protein Modification and Disease, School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
- Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Binggong Zhao
- Key Laboratory of Protein Modification and Disease, School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Jie Kang
- Key Laboratory of Protein Modification and Disease, School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Shujing Li
- Key Laboratory of Protein Modification and Disease, School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
| | - Huijian Wu
- Key Laboratory of Protein Modification and Disease, School of Bioengineering, Dalian University of Technology, Dalian, Liaoning, China
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15
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Safiri S, Nejadghaderi SA, Noori M, Sullman MJM, Collins GS, Kaufman JS, Kolahi AA. Burden of diseases and injuries attributable to alcohol consumption in the Middle East and North Africa region, 1990-2019. Sci Rep 2022; 12:19301. [PMID: 36369336 PMCID: PMC9652338 DOI: 10.1038/s41598-022-22901-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 10/20/2022] [Indexed: 11/13/2022] Open
Abstract
Alcohol consumption is associated with a number of diseases and injuries, including cardiovascular diseases, cancers, mental and neurological disorders, as well as transport-related injuries. This article reports the alcohol-attributable burden of diseases and injuries at the regional and national levels in the Middle East and North Africa (MENA) region between 1990 and 2019, by sex, age, underlying cause, and Socio-demographic Index (SDI). The regional deaths and disability-adjusted life-years (DALYs) attributable to alcohol consumption were reported for the MENA region, between 1990 and 2019, using the methodological framework and analytical strategies adopted by the Global Burden of Disease (GBD) study 2019. The estimates were all reported as counts, population-attributable fractions, and age-standardised rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). Also, the average annual percentage changes were used to represent the trends of age-standardised rates. In 2019, there were an estimated 22.0 thousand deaths (95% UI: 16.1-29.4) and 1.1 million DALYs (0.8-1.3) attributable to alcohol consumption in the MENA region. The number of DALYs attributable to alcohol consumption were much higher in men (878.0 thousand, 691.4-1104.8) than among women (181.8, 138.6-232.0). The overall age-standardised death and DALY rates attributable to alcohol consumption decreased by 34.5% (13.2-48.3) and 31.9% (16.9-42.5), respectively, over the study period. Egypt (10.1 [5.7-16.6]) and Kuwait (1.1 [0.8-1.5]) had the highest and lowest age-standardised death rates attributable to alcohol consumption, respectively. In 2019, the number of deaths and DALYs in the MENA region were highest in those aged 60-64 and 50-54 years, respectively. A negative association was observed between a country's SDI and their corresponding age-standardised DALY rates over the period 1990 to 2019. Digestive diseases were the main contributor to the alcohol-attributable burden. Over 1990-2019, the regional deaths and DALYs of diseases and injuries attributable to alcohol consumption decreased with AAPC of - 1.45 (- 1.78 to - 1.12) and - 1.31 (- 1.46 to - 1.15), respectively. The death and DALY rates attributable to alcohol consumption in the MENA region have decreased over the past three decades. Further decreases can be facilitated by implementing country-level policies and increasing public awareness.
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Affiliation(s)
- Saeid Safiri
- Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Seyed Aria Nejadghaderi
- Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Maryam Noori
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mark J M Sullman
- Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
- Department of Social Sciences, University of Nicosia, Nicosia, Cyprus
| | - Gary S Collins
- Centre for Statistics in Medicine, NDORMS, Botnar Research Centre, University of Oxford, Oxford, UK
- NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Jay S Kaufman
- Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Ali-Asghar Kolahi
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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16
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Shalabi SF, LaBarge MA. Cellular and molecular mechanisms of breast cancer susceptibility. Clin Sci (Lond) 2022; 136:1025-1043. [PMID: 35786748 DOI: 10.1042/cs20211158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/16/2022] [Accepted: 06/22/2022] [Indexed: 11/17/2022]
Abstract
There is a plethora of recognized risk factors for breast cancer (BC) with poorly understood or speculative biological mechanisms. The lack of prevention options highlights the importance of understanding the mechanistic basis of cancer susceptibility and finding new targets for breast cancer prevention. Until now, we have understood risk and cancer susceptibility primarily through the application of epidemiology and assessing outcomes in large human cohorts. Relative risks are assigned to various human behaviors and conditions, but in general the associations are weak and there is little understanding of mechanism. Aging is by far the greatest risk factor for BC, and there are specific forms of inherited genetic risk that are well-understood to cause BC. We propose that bringing focus to the biology underlying these forms of risk will illuminate biological mechanisms of BC susceptibility.
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Affiliation(s)
- Sundus F Shalabi
- Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Medical Research Center, Al-Quds University, Jerusalem, Palestine
| | - Mark A LaBarge
- Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Center for Cancer and Aging, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Center for Cancer Biomarkers Research (CCBIO), Bergen, Norway
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17
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Chang T, Yen T, Wei C, Hsiao T, Chen I. Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol-related disorder and cancer. Cancer Med 2022; 12:747-759. [PMID: 35670037 PMCID: PMC9844601 DOI: 10.1002/cam4.4920] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/18/2022] [Accepted: 05/24/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol-related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol-related disorder and cancer. METHODS This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression. RESULTS Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol-related disorders and was related to an increased risk of alcohol-related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR) = 1.56, p = 0.0009], cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes. CONCLUSION rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol-related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high-risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.
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Affiliation(s)
- Ting‐Gang Chang
- Department of PsychiatryTaichung Veterans General HospitalTaichungTaiwan,School of PsychologyChung Shan Medical UniversityTaichungTaiwan
| | - Ting‐Ting Yen
- Department of OtorhinolaryngologyTaichung Veterans General HospitalTaichungTaiwan,School of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Chia‐Yi Wei
- Department of Medical ResearchTaichung Veterans General HospitalTaichungTaiwan
| | - Tzu‐Hung Hsiao
- Department of Medical ResearchTaichung Veterans General HospitalTaichungTaiwan,Department of Public Health, College of MedicineFu Jen Catholic UniversityNew Taipei CityTaiwan,Institute of Genomics and BioinformaticsNational Chung Hsing UniversityTaichungTaiwan
| | - I‐Chieh Chen
- Department of Medical ResearchTaichung Veterans General HospitalTaichungTaiwan
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18
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Hussain A, Bourguet-Kondracki ML, Hussain F, Rauf A, Ibrahim M, Khalid M, Hussain H, Hussain J, Ali I, Khalil AA, Alhumaydhi FA, Khan M, Hussain R, Rengasamy KRR. The potential role of dietary plant ingredients against mammary cancer: a comprehensive review. Crit Rev Food Sci Nutr 2022; 62:2580-2605. [DOI: 10.1080/10408398.2020.1855413] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Amjad Hussain
- Department of Chemistry, University of Okara, Okara, Pakistan
- Laboratoire Molécules de Communication et Adaptation des Micro-organismes, UMR 7245 MNHN-CNRS, Muséum National d’Histoire Naturelle, Paris, France
- Department of Applied Chemistry, Government College University, Faisalabad, Pakistan
| | - Marie-Lise Bourguet-Kondracki
- Laboratoire Molécules de Communication et Adaptation des Micro-organismes, UMR 7245 MNHN-CNRS, Muséum National d’Histoire Naturelle, Paris, France
| | - Farhad Hussain
- Department of Applied Chemistry, Government College University, Faisalabad, Pakistan
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, Khyber Pukhtanuk (KP), Pakistan
| | - Muhammad Ibrahim
- Department of Applied Chemistry, Government College University, Faisalabad, Pakistan
| | - Muhammad Khalid
- Department of Chemistry, Khwaja Fareed University of Engineering & Information Technology, Punjab, Pakistan
| | - Hidayat Hussain
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle (Salle), Germany
| | - Javid Hussain
- Department of Biological Sciences & Chemistry, College of Arts and Sciences, University of Nizwa, Nizwa, Sultanate of Oman
| | - Iftikhar Ali
- Department of Chemistry, Karakoram International University, Gilgit, Pakistan
| | - Anees Ahmed Khalil
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Muhammad Khan
- Department of Chemistry, University of Okara, Okara, Pakistan
| | - Riaz Hussain
- Department of Chemistry, University of Okara, Okara, Pakistan
| | - Kannan R. R. Rengasamy
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
- Faculty of Environment and Chemical Engineering, Duy Tan University, Da Nang, Vietnam
- Indigenous Knowledge Systems Centre, Faculty of Natural and Agricultural Sciences, North-West University, Mmabatho, South Africa
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19
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Yu T, Ye DM. The epidemiologic factors associated with breast density: A review. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2022; 27:53. [PMID: 36092490 PMCID: PMC9450246 DOI: 10.4103/jrms.jrms_962_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/14/2022] [Accepted: 01/26/2022] [Indexed: 11/04/2022]
Abstract
In recent years, some studies have evaluated the epidemiologic factors associated with breast density. However, the variant and inconsistent results exist. In addition, breast density has been proved to be a significant risk factor associated with breast cancer. Our review summarized the published studies and emphasized the crucial factors including epidemiological factors associated with breast density. In addition, we also discussed the potential reasons for the discrepant results with risk factors. To decrease the incidence and mortality rates for breast cancer, in clinical practice, breast density should be included for clinical risk models in addition to epidemiological factors, and physicians should get more concentrate on those women with risk factors and provide risk-based breast cancer screening regimens.
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20
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A Review of Breast Cancer Risk Factors in Adolescents and Young Adults. Cancers (Basel) 2021; 13:cancers13215552. [PMID: 34771713 PMCID: PMC8583289 DOI: 10.3390/cancers13215552] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/29/2021] [Accepted: 11/03/2021] [Indexed: 12/26/2022] Open
Abstract
Simple Summary Cancer diagnosed in patients between the ages of 15 and 39 deserves special consideration. Diagnoses within this cohort of adolescents and young adults include childhood cancers which present at an older age than expected, or an early presentation of cancers that are typically observed in older adults, such as breast cancer. Cancers within this age group are associated with worse disease-free and overall survival rates, and the incidence of these cases are rising. Knowing an individual’s susceptibility to disease can change their clinical management and allow for the risk-testing of relatives. This review discusses the risk factors that contribute to breast cancer in this unique cohort of patients, including inherited genetic risk factors, as well as environmental and lifestyle factors. We also describe risk models that allow clinicians to quantify a patient’s lifetime risk of developing disease. Abstract Cancer in adolescents and young adults (AYAs) deserves special consideration for several reasons. AYA cancers encompass paediatric malignancies that present at an older age than expected, or early-onset of cancers that are typically observed in adults. However, disease diagnosed in the AYA population is distinct to those same cancers which are diagnosed in a paediatric or older adult setting. Worse disease-free and overall survival outcomes are observed in the AYA setting, and the incidence of AYA cancers is increasing. Knowledge of an individual’s underlying cancer predisposition can influence their clinical care and may facilitate early tumour surveillance strategies and cascade testing of at-risk relatives. This information can further influence reproductive decision making. In this review we discuss the risk factors contributing to AYA breast cancer, such as heritable predisposition, environmental, and lifestyle factors. We also describe a number of risk models which incorporate genetic factors that aid clinicians in quantifying an individual’s lifetime risk of disease.
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21
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Zheng L, Lin Y, Zhong S. ROS Signaling-Mediated Novel Biological Targets: Brf1 and RNA Pol III Genes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5888432. [PMID: 34646425 PMCID: PMC8505076 DOI: 10.1155/2021/5888432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/20/2021] [Indexed: 11/18/2022]
Abstract
Biomolecule metabolism produces ROS (reactive oxygen species) under physiological and pathophysiological conditions. Dietary factors (alcohol) and carcinogens (EGF, DEN, and MNNG) also induce the release of ROS. ROS often causes cell stress and tissue injury, eventually resulting in disorders or diseases of the body through different signaling pathways. Normal metabolism of protein is critically important to maintain cellular function and body health. Brf1 (transcript factor II B-related factor 1) and its target genes, RNA Pol III genes (RNA polymerase III-dependent genes), control the process of protein synthesis. Studies have demonstrated that the deregulation of Brf1 and its target genes is tightly linked to cell proliferation, cell transformation, tumor development, and human cancers, while alcohol, EGF, DEN, and MNNG are able to induce the deregulation of these genes through different signaling pathways. Therefore, it is very important to emphasize the roles of these signaling events mediating the processes of Brf1 and RNA Pol III gene transcription. In the present paper, we mainly summarize our studies on signaling events which mediate the deregulation of these genes in the past dozen years. These studies indicate that Brf1 and RNA Pol III genes are novel biological targets of ROS.
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Affiliation(s)
- Liling Zheng
- First Hospital of Quanzhou Affiliated to Fujian Medical University, China
| | - Yongluan Lin
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Shuping Zhong
- Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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22
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Rumgay H, Murphy N, Ferrari P, Soerjomataram I. Alcohol and Cancer: Epidemiology and Biological Mechanisms. Nutrients 2021; 13:3173. [PMID: 34579050 PMCID: PMC8470184 DOI: 10.3390/nu13093173] [Citation(s) in RCA: 174] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 09/03/2021] [Accepted: 09/09/2021] [Indexed: 12/16/2022] Open
Abstract
Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol's metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.
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Affiliation(s)
- Harriet Rumgay
- Cancer Surveillance Branch, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France;
| | - Neil Murphy
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France; (N.M.); (P.F.)
| | - Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France; (N.M.); (P.F.)
| | - Isabelle Soerjomataram
- Cancer Surveillance Branch, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France;
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23
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MicroRNA and cyclooxygenase-2 in breast cancer. Clin Chim Acta 2021; 522:36-44. [PMID: 34389281 DOI: 10.1016/j.cca.2021.08.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/30/2021] [Accepted: 08/07/2021] [Indexed: 12/24/2022]
Abstract
Cancer remains a major public health problem worldwide and the latest statistics show that breast cancer (BC) is among the most frequent in women. MicroRNAs (miRNAs; miRs) and cyclooxygenase-2 (COX-2) are new diagnostic and therapeutic biomarkers for monitoring BC. COX-2 is a prominent tumor-associated inflammatory factor highly expressed in human tumor cells, including BC. Expression of COX-2 contributes to tumor growth, metastasis and recurrence. MiRs are a group of short (~22 nucleotides), noncoding regulatory RNAs that downregulate gene expression post-transcriptionally and play vital roles in regulating cancer development and progression. Interestingly, there are a group of miRNAs differentially expressed in breast tumor tissue. Understanding the pathway linking miRNAs to COX-2 can provide novel insight for suppressing COX-2 expression via gene silencing thereby leading to the development of selective miRNA inhibitors. Further research can also reveal key intermediate players and their potential as therapeutic targets. Given the association between different miRNAs and COX-2 expression in BC, this review presents a comprehensive overview of the current literature concerning how miRNAs and COX-2 signaling interact in BC progression.
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24
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Rumgay H, Shield K, Charvat H, Ferrari P, Sornpaisarn B, Obot I, Islami F, Lemmens VEPP, Rehm J, Soerjomataram I. Global burden of cancer in 2020 attributable to alcohol consumption: a population-based study. Lancet Oncol 2021; 22:1071-1080. [PMID: 34270924 PMCID: PMC8324483 DOI: 10.1016/s1470-2045(21)00279-5] [Citation(s) in RCA: 342] [Impact Index Per Article: 85.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/28/2021] [Accepted: 04/30/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Alcohol use is causally linked to multiple cancers. We present global, regional, and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally. METHODS In this population-based study, population attributable fractions (PAFs) calculated using a theoretical minimum-risk exposure of lifetime abstention and 2010 alcohol consumption estimates from the Global Information System on Alcohol and Health (assuming a 10-year latency period between alcohol consumption and cancer diagnosis), combined with corresponding relative risk estimates from systematic literature reviews as part of the WCRF Continuous Update Project, were applied to cancer incidence data from GLOBOCAN 2020 to estimate new cancer cases attributable to alcohol. We also calculated the contribution of moderate (<20 g per day), risky (20-60 g per day), and heavy (>60 g per day) drinking to the total alcohol-attributable cancer burden, as well as the contribution by 10 g per day increment (up to a maximum of 150 g). 95% uncertainty intervals (UIs) were estimated using a Monte Carlo-like approach. FINDINGS Globally, an estimated 741 300 (95% UI 558 500-951 200), or 4·1% (3·1-5·3), of all new cases of cancer in 2020 were attributable to alcohol consumption. Males accounted for 568 700 (76·7%; 95% UI 422 500-731 100) of total alcohol-attributable cancer cases, and cancers of the oesophagus (189 700 cases [110 900-274 600]), liver (154 700 cases [43 700-281 500]), and breast (98 300 cases [68 200-130 500]) contributed the most cases. PAFs were lowest in northern Africa (0·3% [95% UI 0·1-3·3]) and western Asia (0·7% [0·5-1·2]), and highest in eastern Asia (5·7% [3·6-7·9]) and central and eastern Europe (5·6% [4·6-6·6]). The largest burden of alcohol-attributable cancers was represented by heavy drinking (346 400 [46·7%; 95% UI 227 900-489 400] cases) and risky drinking (291 800 [39·4%; 227 700-333 100] cases), whereas moderate drinking contributed 103 100 (13·9%; 82 600-207 200) cases, and drinking up to 10 g per day contributed 41 300 (35 400-145 800) cases. INTERPRETATION Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to prevent the burden of alcohol-attributable cancers. FUNDING None.
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Affiliation(s)
- Harriet Rumgay
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.
| | - Kevin Shield
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Hadrien Charvat
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - Bundit Sornpaisarn
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Isidore Obot
- Centre for Research and Information on Substance Abuse, Uyo, Nigeria
| | - Farhad Islami
- Surveillance and Health Equity Research, American Cancer Society, Atlanta, GA, USA
| | - Valery E P P Lemmens
- Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands; Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, Netherlands
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of International Health Projects, Institute for Leadership and Health Management, Sechenov First Moscow State Medical University, Moscow, Russia; Institute of Clinical Psychology and Psychotherapy, and Center for Clinical Epidemiology and Longitudinal Studies, Technische Universität Dresden, Dresden, Germany
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Pandya N, Bhagwat SR, Kumar A. Regulatory role of Non-canonical DNA Polymorphisms in human genome and their relevance in Cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188594. [PMID: 34303788 DOI: 10.1016/j.bbcan.2021.188594] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/19/2021] [Accepted: 07/19/2021] [Indexed: 12/17/2022]
Abstract
DNA has the ability to form polymorphic structures like canonical duplex DNA and non-canonical triplex DNA, Cruciform, Z-DNA, G-quadruplex (G4), i-motifs, and hairpin structures. The alteration in the form of DNA polymorphism in the response to environmental changes influences the gene expression. Non-canonical structures are engaged in various biological functions, including chromatin epigenetic and gene expression regulation via transcription and translation, as well as DNA repair and recombination. The presence of non-canonical structures in the regulatory region of the gene alters the gene expression and affects the cellular machinery. Formation of non-canonical structure in the regulatory site of cancer-related genes either inhibits or dysregulate the gene function and promote tumour formation. In the current article, we review the influence of non-canonical structure on the regulatory mechanisms in human genome. Moreover, we have also discussed the relevance of non-canonical structures in cancer and provided information on the drugs used for their treatment by targeting these structures.
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Affiliation(s)
- Nirali Pandya
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, India
| | - Sonali R Bhagwat
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, India
| | - Amit Kumar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore 453552, India.
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26
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Tateishi-Karimata H, Sugimoto N. Roles of non-canonical structures of nucleic acids in cancer and neurodegenerative diseases. Nucleic Acids Res 2021; 49:7839-7855. [PMID: 34244785 PMCID: PMC8373145 DOI: 10.1093/nar/gkab580] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 06/17/2021] [Accepted: 07/06/2021] [Indexed: 12/14/2022] Open
Abstract
Cancer and neurodegenerative diseases are caused by genetic and environmental factors. Expression of tumour suppressor genes is suppressed by mutations or epigenetic silencing, whereas for neurodegenerative disease-related genes, nucleic acid-based effects may be presented through loss of protein function due to erroneous protein sequences or gain of toxic function from extended repeat transcripts or toxic peptide production. These diseases are triggered by damaged genes and proteins due to lifestyle and exposure to radiation. Recent studies have indicated that transient, non-canonical structural changes in nucleic acids in response to the environment can regulate the expression of disease-related genes. Non-canonical structures are involved in many cellular functions, such as regulation of gene expression through transcription and translation, epigenetic regulation of chromatin, and DNA recombination. Transcripts generated from repeat sequences of neurodegenerative disease-related genes form non-canonical structures that are involved in protein transport and toxic aggregate formation. Intracellular phase separation promotes transcription and protein assembly, which are controlled by the nucleic acid structure and can influence cancer and neurodegenerative disease progression. These findings may aid in elucidating the underlying disease mechanisms. Here, we review the influence of non-canonical nucleic acid structures in disease-related genes on disease onset and progression.
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Affiliation(s)
- Hisae Tateishi-Karimata
- Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
| | - Naoki Sugimoto
- Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.,Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
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27
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Sharma R. Examination of incidence, mortality and disability-adjusted life years and risk factors of breast cancer in 49 Asian countries, 1990-2019: estimates from Global Burden of Disease Study 2019. Jpn J Clin Oncol 2021; 51:826-835. [PMID: 33621341 DOI: 10.1093/jjco/hyab004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND This study presents an up-to-date, comprehensive and comparative examination of breast cancer's temporal patterns in females in Asia in last three decades. METHODS The estimates of incidence, mortality, disability-adjusted-life-years and risk factors of breast cancer in females in 49 Asian countries were retrieved from Global Burden of Disease 2019 study. RESULTS In Asia, female breast cancer incidence grew from 245 045[226 259-265 260] in 1990 to 914 878[815 789-1025 502] in 2019 with age-standardized incidence rate rising from 21.2/100 000[19.6-22.9] to 35.9/100 000[32.0-40.2] between 1990 and 2019. The death counts more than doubled from 136 665[126 094-148 380] to 337 822[301 454-375 251]. The age-standardized mortality rate rose marginally between 1990 and 2019 (1990: 12.1[11.0-13.1]; 2019: 13.4[12.0-14.9]). In 2019, age-standardized incidence rate varied from 17.2/100 000[13.95-21.4] in Mongolia to 122.5[92.1-160.7] in Lebanon and the age-standardized mortality rate varied 4-fold from 8.0/100 000 [7.2-8.8] in South Korea to 51.9[39.0-69.8] in Pakistan. High body mass index (5.6%), high fasting plasma glucose (5.6%) and secondhand smoke (3.5%) were the main contributory risk factors to all-age disability-adjusted-life-years due to breast cancer in Asia. CONCLUSION With growing incidence, escalating dietary and behavioural risk factors and lower survival rates due to late-disease presentation in low- and medium-income countries of Asia, breast cancer has become a significant public health threat. Its rising burden calls for increasing breast cancer awareness, preventive measures, early-stage detection and cost-effective therapeutics in Asia.
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Affiliation(s)
- Rajesh Sharma
- Assistant Professor, University School of Management and Entrepreneurship, Delhi Technological University, Delhi, India
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28
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Xiao X, Zhang Z, Luo R, Peng R, Sun Y, Wang J, Chen X. Identification of potential oncogenes in triple-negative breast cancer based on bioinformatics analyses. Oncol Lett 2021; 21:363. [PMID: 33747220 PMCID: PMC7967975 DOI: 10.3892/ol.2021.12624] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 02/02/2021] [Indexed: 12/28/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is a subtype with high rates of metastasis, poor prognosis and limited therapeutic options. The present study aimed to identify the potential pivotal genes for prognosis and treatment in TNBC. A total of two microarray expression datasets, GSE38959 and GSE65212, were downloaded from the Gene Expression Omnibus database, and RNA-sequencing data of breast cancer from The Cancer Genome Atlas database were analyzed to screen out differentially expressed genes (DEGs) between TNBC tissues and normal tissues. The intersection of DEGs was submitted to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A protein-protein interaction (PPI) network was constructed and visualized using Cytoscape software. Furthermore, module, centrality and survival analyses were performed to identify the potential hub genes. Reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of key genes in TNBC samples, and 377 DEGs were identified. Functional analysis revealed that the DEGs were significantly involved in cell cycle process, nuclear division and the p53 signaling pathway. A PPI network was constructed with these DEGs, and 66 core genes with high centrality features in module 1 were selected. Relapse-free survival analysis confirmed that high expression levels of five genes [cyclin B1 (CCNB1), GINS complex subunit 2, non-SMC condensin I complex subunit G (NCAPG), minichromosome maintenance 4 (MCM4) and ribonucleotide reductase regulatory subunit M2 (RRM2)] were significantly associated with poor prognosis in TNBC. RT-qPCR analysis demonstrated that CCNB1, NCAPG, MCM4 and RRM2 were significantly upregulated in 25 TNBC tissues compared with adjacent normal breast tissues. Furthermore, gene set enrichment analysis revealed that CCNB1, NCAPG, MCM4 and RRM2 were closely associated with tumor proliferation. Taken together, these results suggest that CCNB1, NCAPG, MCM4 and RRM2 are associated with tumorigenesis and TNBC progression, and thus may act as promising prognostic biomarkers and therapeutic targets for TNBC.
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Affiliation(s)
- Xiao Xiao
- Department of Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
| | - Zheng Zhang
- Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Ruihan Luo
- Department of Bioinformatics, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Rui Peng
- Department of Bioinformatics, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Yan Sun
- Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Jia Wang
- Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Xin Chen
- Department of Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
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29
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Iwase M, Matsuo K, Koyanagi YNY, Ito H, Tamakoshi A, Wang C, Utada M, Ozasa K, Sugawara Y, Tsuji I, Sawada N, Tanaka S, Nagata C, Kitamura Y, Shimazu T, Mizoue T, Naito M, Tanaka K, Inoue M. Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies. Int J Cancer 2021; 148:2736-2747. [PMID: 33497475 DOI: 10.1002/ijc.33478] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/05/2021] [Accepted: 01/11/2021] [Indexed: 01/22/2023]
Abstract
Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.
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Affiliation(s)
- Madoka Iwase
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.,Department of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.,Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuriko N Y Koyanagi
- Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Hidemi Ito
- Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan.,Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akiko Tamakoshi
- Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Chaochen Wang
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Mai Utada
- Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan
| | - Kotaro Ozasa
- Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan
| | - Yumi Sugawara
- Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ichiro Tsuji
- Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Norie Sawada
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Shiori Tanaka
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Chisato Nagata
- Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuri Kitamura
- Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
| | - Tetsuya Mizoue
- Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Mariko Naito
- Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Keitaro Tanaka
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Manami Inoue
- Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.,Department of Cancer Epidemiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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30
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Helbig M, Vesper AS, Beyer I, Fehm T. Does Nutrition Affect Endometriosis? Geburtshilfe Frauenheilkd 2021; 81:191-199. [PMID: 33574623 PMCID: PMC7870287 DOI: 10.1055/a-1207-0557] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 06/24/2020] [Indexed: 02/08/2023] Open
Abstract
Endometriosis is a hormone-related, chronic inflammation in women of childbearing age. The aetiology and pathogenesis of endometriosis are not yet fully understood. For other illnesses classed as lifestyle diseases, the link between nutrition and pathogenesis has already been researched and proven. With regard to these findings, the question continues to arise as to whether and how a specific diet and lifestyle could also influence pathogenesis and the progression of endometriosis. The aim of this review is to examine the data and determine what influence nutrition has on the development of endometriosis or on existing disease. The study results currently available do not permit a clear, scientific recommendation or indicate a detailed diet. In summary, it can be said that fish oil capsules in combination with vitamin B 12 have been associated with a positive effect on endometriosis symptoms (particularly of dysmenorrhoea). Alcohol and increased consumption of red meat and trans fats are associated with a negative effect. The results of the studies listed with regard to fruit and vegetables, dairy products, unsaturated fats, fibre, soy products and coffee are not clear. Therefore, the general recommendations for a balanced and varied diet in line with the guidelines of the Deutsche Gesellschaft für Ernährung e. V. [German Nutrition Society] apply, along with the recommendation to cut out alcohol. In order to be able to derive more concrete recommendations, we require further studies to investigate the influence of nutrition on endometriosis.
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Affiliation(s)
- Martina Helbig
- Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Anne-Sophie Vesper
- Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Ines Beyer
- Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Tanja Fehm
- Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
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Steinberg J, Yap S, Goldsbury D, Nair-Shalliker V, Banks E, Canfell K, O'Connell DL. Large-scale systematic analysis of exposure to multiple cancer risk factors and the associations between exposure patterns and cancer incidence. Sci Rep 2021; 11:2343. [PMID: 33504831 PMCID: PMC7841154 DOI: 10.1038/s41598-021-81463-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 12/28/2020] [Indexed: 12/29/2022] Open
Abstract
Exposures to cancer risk factors such as smoking and alcohol are not mutually independent. We aimed to identify risk factor exposure patterns and their associations with sociodemographic characteristics and cancer incidence. We considered 120,771 female and, separately, 100,891 male participants of the Australian prospective cohort 45 and Up Study. Factor analysis grouped 36 self-reported variables into 8 combined factors each for females (largely representing 'smoking', 'alcohol', 'vigorous exercise', 'age at childbirth', 'Menopausal Hormone Therapy', 'parity and breastfeeding', 'standing/sitting', 'fruit and vegetables') and males (largely representing 'smoking', 'alcohol', 'vigorous exercise', 'urology and health', 'moderate exercise', 'standing/sitting', 'fruit and vegetables', 'meat and BMI'). Associations with cancer incidence were investigated using multivariable logistic regression (4-8 years follow-up: 6193 females, 8749 males diagnosed with cancer). After multiple-testing correction, we identified 10 associations between combined factors and cancer incidence for females and 6 for males, of which 14 represent well-known relationships (e.g. bowel cancer: females 'smoking' factor Odds Ratio (OR) 1.16 (95% Confidence Interval (CI) 1.08-1.25), males 'smoking' factor OR 1.15 (95% CI 1.07-1.23)), providing evidence for the validity of this approach. The catalogue of associations between exposure patterns, sociodemographic characteristics, and cancer incidence can help inform design of future studies and targeted prevention programmes.
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Affiliation(s)
- Julia Steinberg
- Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia.
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.
| | - Sarsha Yap
- Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia
| | - David Goldsbury
- Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia
| | - Visalini Nair-Shalliker
- Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
| | - Emily Banks
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia
| | - Karen Canfell
- Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Prince of Wales Clinical School, UNSW Medicine, Sydney, NSW, Australia
| | - Dianne L O'Connell
- Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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Jung SY, Papp JC, Sobel EM, Pellegrini M, Yu H, Zhang ZF. Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene-gene and gene-lifestyle interaction. Sci Rep 2021; 11:1058. [PMID: 33441805 PMCID: PMC7807068 DOI: 10.1038/s41598-020-80197-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 12/17/2020] [Indexed: 11/13/2022] Open
Abstract
Molecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women's Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene-lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.
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Affiliation(s)
- Su Yon Jung
- Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, 700 Tiverton Ave, 3-264 Factor Building, Los Angeles, CA, 90095, USA.
| | - Jeanette C Papp
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Eric M Sobel
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
- Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Matteo Pellegrini
- Department of Molecular, Cell and Developmental Biology, Life Sciences Division, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Herbert Yu
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, 90095, USA
- Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
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Alcohol. Alcohol 2021. [DOI: 10.1016/b978-0-12-816793-9.00001-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Vegunta S, Lester SP, Pruthi S, Mussallem DM. Effects of major lifestyle factors on breast cancer risk: impact of weight, nutrition, physical activity, alcohol and tobacco. BREAST CANCER MANAGEMENT 2020. [DOI: 10.2217/bmt-2020-0033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Breast cancer (BC) is the most commonly diagnosed cancer and second most common cause of cancer death in US women. Family history and genetics are well-known BC risk factors, but they only account for 15–20% of BC cases. Therefore, in addition to family history, healthcare providers must consider a woman’s modifiable and nonmodifiable personal risk factors that are associated with an increase in BC risk. The World Cancer Research Fund/American Institute for Cancer Research estimate that 30% of BC cases in the US are preventable. Lifestyle education is imperative given the magnitude of BC occurrence. Evidence supports prevention as an effective, long-term strategy for reducing risk. Healthcare providers are key stakeholders in empowering patients to adopt a healthy lifestyle for primary BC prevention. In this paper, we review the available evidence on modifiable BC risk including weight management, nutrition, physical activity, alcohol and tobacco use and provide strategies to counsel patients on lifestyle modifications.
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Affiliation(s)
- Suneela Vegunta
- Division of Women’s Health Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA
| | - Sara P Lester
- Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Sandhya Pruthi
- Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Dawn M Mussallem
- Jacoby Center for Breast Health, Mayo Clinic, Jacksonville, FL, USA
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Ho C, Lin CY. Genes Associated with Calcium Signaling are Involved in Alcohol-Induced Breast Cancer Growth. Alcohol Clin Exp Res 2020; 45:79-91. [PMID: 33222221 DOI: 10.1111/acer.14521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/26/2020] [Accepted: 11/16/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Alcohol consumption is a risk factor for breast cancer, contributing to up to nearly 23,000 new cases each year. Mechanistic studies show that alcohol increases tumor aggressiveness and metastatic potential, promotes angiogenesis, induces chronic inflammation, and dysregulates RNA polymerase III-related genes. Alcohol has also been shown to affect estrogen signaling in breast cancer, including in our study of the transcriptomic effects of alcohol in breast cancer cells. METHODS To elucidate mechanisms of action of alcohol in breast cancer, we carried out secondary analyses of our alcohol-responsive transcriptome data using gene ontology and pathway databases and analysis tools and cistromic data analysis of candidate transcription factors which may mediate the transcriptomic alterations. Predicted alcohol-responsive pathways and mechanisms were perturbed and examined experimentally in breast cancer cells. The clinical relevance of identified genes was determined by expression profiles in patient samples and correlation with disease outcomes and alcohol consumption in previously published study cohorts. RESULTS Gene ontology analysis showed that alcohol alters the expression of many metabolism-related genes, and cistromic data of differentially expressed genes revealed the potential involvement of nuclear factor of activated T cells 3 (NFATC3) in mediating the transcriptomic effects of alcohol. Pathway analysis also predicted regulation of calcium signaling by alcohol in breast cancer cells. Chemical perturbation of this pathway reversed the effect of alcohol on breast cancer cell growth and reduced the elevated cytosolic Ca2+ levels induced by alcohol. Expression levels of alcohol-responsive genes in tumor samples from breast cancer patients are associated with poor disease outcomes. Moreover, expression of some of these genes was altered in breast cancer patients who consumed alcohol previously as compared to those who did not drink. CONCLUSION Alcohol alters expression of genes that regulate intracellular calcium levels and downstream signaling pathways which drive breast cancer cell proliferation and disease progression.
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Affiliation(s)
- Charles Ho
- From the, Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Science & Engineering Research Center, Houston, Texas, USA
| | - Chin-Yo Lin
- From the, Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Science & Engineering Research Center, Houston, Texas, USA
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Abstract
Despite decades of laboratory, epidemiological and clinical research, breast cancer incidence continues to rise. Breast cancer remains the leading cancer-related cause of disease burden for women, affecting one in 20 globally and as many as one in eight in high-income countries. Reducing breast cancer incidence will likely require both a population-based approach of reducing exposure to modifiable risk factors and a precision-prevention approach of identifying women at increased risk and targeting them for specific interventions, such as risk-reducing medication. We already have the capacity to estimate an individual woman's breast cancer risk using validated risk assessment models, and the accuracy of these models is likely to continue to improve over time, particularly with inclusion of newer risk factors, such as polygenic risk and mammographic density. Evidence-based risk-reducing medications are cheap, widely available and recommended by professional health bodies; however, widespread implementation of these has proven challenging. The barriers to uptake of, and adherence to, current medications will need to be considered as we deepen our understanding of breast cancer initiation and begin developing and testing novel preventives.
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Affiliation(s)
- Kara L Britt
- Breast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia.
| | - Jack Cuzick
- Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
| | - Kelly-Anne Phillips
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia
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Feng Y, Powell L, Vassallo AJ, Hamer M, Stamatakis E. Does adequate physical activity attenuate the associations of alcohol and alcohol‐related cancer mortality? A pooled study of 54 686 British adults. Int J Cancer 2020; 147:2754-2763. [DOI: 10.1002/ijc.33052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 04/16/2020] [Accepted: 04/24/2020] [Indexed: 12/22/2022]
Affiliation(s)
- Yingyu Feng
- Kolling Institute, Northern Clinical School University of Sydney Sydney New South Wales Australia
| | - Lauren Powell
- Charles Perkins Centre, School of Public Health, Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Amy Jo Vassallo
- Charles Perkins Centre, School of Public Health, Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Mark Hamer
- UCL Faculty Medical Sciences Institute Sport Exercise & Health London UK
| | - Emmanuel Stamatakis
- Charles Perkins Centre, School of Public Health, Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
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Hong Z, Fang Z, Lei J, Shi G, Zhang Y, He Z, Li B W, Zhong S. The significance of Runx2 mediating alcohol-induced Brf1 expression and RNA Pol III gene transcription. Chem Biol Interact 2020; 323:109057. [PMID: 32198086 PMCID: PMC7261693 DOI: 10.1016/j.cbi.2020.109057] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 03/10/2020] [Indexed: 02/05/2023]
Abstract
Runx2 (Runt-related transcription factor 2) is a key transcription factor which is associated with osteoblast differentiation and expressed in ER+ (estrogen receptor positive) human breast cancer cell lines. Runx2 also participates in mammary gland development. Deregulation of RNA Pol III genes (polymerase III-dependent genes) is tightly linked to tumor development, while Brf1 (TFIIB-related factor 1) specifically regulates these gene transcription. However, nothing is known about the effect of Runx2 on Brf1 expression and Pol III gene transcription. Expression of Runx2, Brf1 and Pol III genes from the samples of human breast cancer and cell culture model were determined by the assays of RT-qPCR, immunoblot, luciferase reporter activity, immunohistochemistry, chromatin immunoprecipitation and Immunofluorescence. High expression of Runx2 is observed in the cases of breast cancer. The patients of high Runx2 expression at early stages display longer survival period, whereas the cases of high Runx2 at advanced stages reveal faster recurrence. The identification of signaling pathway indicates that JNK1 and c-Jun mediate Runx2 transcription. Repression of Runx2 reduces Brf1 expression and Pol III gene transcription. Further analysis indicates that Runx2 is colocalized with Brf1 in nucleus of breast cancer tissue. Both Runx2 and Brf1 synergistically modulate Pol III gene transcription. These studies indicate that Brf1 overexpression is able to be used as an early diagnosis biomarker of breast cancer, while high Runx2 expression indicates long survival period and faster recurrence. Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer.
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Affiliation(s)
- Zaifa Hong
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Zeng Fang
- Laboratory of General Surgery and Department of Breast and Thyroid Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junxia Lei
- School of Medicine, South China University of Technology, China; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Ganggang Shi
- Department of Pharmacology, Shantou University Medical College, China
| | - Yanmei Zhang
- Department of Pharmacology, Shantou University Medical College, China; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Zhiming He
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China
| | - Wen Li B
- Laboratory of General Surgery and Department of Breast and Thyroid Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Shuping Zhong
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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McBride RB, Fei K, Rothstein JH, Alexeeff SE, Song X, Sakoda LC, McGuire V, Achacoso N, Acton L, Liang RY, Lipson JA, Yaffe MJ, Rubin DL, Whittemore AS, Habel LA, Sieh W. Alcohol and Tobacco Use in Relation to Mammographic Density in 23,456 Women. Cancer Epidemiol Biomarkers Prev 2020; 29:1039-1048. [PMID: 32066618 PMCID: PMC7196522 DOI: 10.1158/1055-9965.epi-19-0348] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 07/27/2019] [Accepted: 02/07/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood. METHODS We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis. RESULTS Alcohol use was positively associated with PD (P trend = 0.01), unassociated with DA (P trend = 0.23), and inversely associated with NDA (P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (P trend = 0.0008), unassociated with DA (P trend = 0.93), and positively associated with NDA (P trend<0.0001). These trends were stronger in normal and overweight women than in obese women. CONCLUSIONS These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA. IMPACT PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health.
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Affiliation(s)
- Russell B McBride
- Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Kezhen Fei
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joseph H Rothstein
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Stacey E Alexeeff
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Xiaoyu Song
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Lori C Sakoda
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Valerie McGuire
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
| | - Ninah Achacoso
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Luana Acton
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Rhea Y Liang
- Department of Radiology, Stanford University School of Medicine, Stanford, California
| | - Jafi A Lipson
- Department of Radiology, Stanford University School of Medicine, Stanford, California
| | - Martin J Yaffe
- Departments of Medical Biophysics and Medical Imaging, University of Toronto, Toronto, Ontario, Canada
| | - Daniel L Rubin
- Department of Radiology, Stanford University School of Medicine, Stanford, California
- Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California
| | - Alice S Whittemore
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
- Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California
| | - Laurel A Habel
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Weiva Sieh
- Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
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Heng YJ, Hankinson SE, Wang J, Alexandrov LB, Ambrosone CB, de Andrade VP, Brufsky AM, Couch FJ, King TA, Modugno F, Vachon CM, Eliassen AH, Tamimi RM, Kraft P. The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network. Cancer Epidemiol Biomarkers Prev 2020; 29:599-605. [PMID: 31932411 PMCID: PMC7060119 DOI: 10.1158/1055-9965.epi-19-1087] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 12/03/2019] [Accepted: 01/07/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The link between modifiable breast cancer risk factors and tumor genomic alterations remains largely unexplored. We evaluated the association of prediagnostic body mass index (BMI), cigarette smoking, and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30), and nine driver mutations (CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK3CA, RUNX1, and TP53) in a subset of The Cancer Genome Atlas (TCGA). METHODS Clinical and genomic data were retrieved from the TCGA database. Risk factor information was collected from four TCGA sites (n = 219 women), including BMI (1 year before diagnosis), cigarette smoking (smokers/nonsmokers), and alcohol consumption (current drinkers/nondrinkers). Multivariable regression analyses were conducted in all tumors and stratified according to estrogen receptor (ER) status. RESULTS Increasing BMI was associated with increasing SCNV in all women (P = 0.039) and among women with ER- tumors (P = 0.031). Smokers had higher SCNV and TSMB versus nonsmokers (P < 0.05 all women). Alcohol drinkers had higher SCNV versus nondrinkers (P < 0.05 all women and among women with ER+ tumors). SBS3 (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER- disease. GATA3 mutation was more likely to occur in women with higher BMI. No association was significant after multiple testing correction. CONCLUSIONS This study provides preliminary evidence that BMI, cigarette smoking, and alcohol consumption can influence breast tumor biology, in particular, DNA alterations. IMPACT This study demonstrates a link between modifiable breast cancer risk factors and tumor genomic alterations.
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Affiliation(s)
- Yujing J Heng
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
- Cancer Research Institute, Beth Israel Deaconess Cancer Center, Boston, Massachusetts
| | - Susan E Hankinson
- Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
| | - Jun Wang
- Department of Preventive Medicine, University of Southern California, Los Angeles, California
| | - Ludmil B Alexandrov
- Departments of Cellular and Molecular Medicine, and Bioengineering, University of California, San Diego, California
| | - Christine B Ambrosone
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | | | - Adam M Brufsky
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Fergus J Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Tari A King
- Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | - Francesmary Modugno
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Celine M Vachon
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
| | - A Heather Eliassen
- Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Rulla M Tamimi
- Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Peter Kraft
- Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
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The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: A systematic review. Breast 2020; 50:95-103. [PMID: 32120064 PMCID: PMC7073883 DOI: 10.1016/j.breast.2020.02.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/10/2020] [Indexed: 11/21/2022] Open
Abstract
Objective The majority of ‘low-risk’ (grade I/II) Ductal Carcinoma In Situ (DCIS) may not progress to invasive breast cancer during a women’s lifetime. Therefore, the safety of active surveillance versus standard surgical treatment for DCIS is prospectively being evaluated in clinical trials. If proven safe and selectively implemented in clinical practice, a significant group of women with low-risk DCIS may forego surgery and radiotherapy in the future. Identification of modifiable and non-modifiable risk factors associated with prognosis after a primary DCIS would also enhance our care of women with low-risk DCIS. Methods To identify modifiable and non-modifiable risk factors for subsequent breast events after DCIS, we performed a systematic literature search in PUBMED, EMBASE and Scopus. Results Six out of the 3870 articles retrieved were included for final data extraction. These six studies included a total of 4950 patients with primary DCIS and 640 recorded subsequent breast events. There was moderate evidence for an association of a family history of breast cancer, premenopausal status, high BMI, and high breast density with a subsequent breast cancer or further DCIS. Conclusion There is a limited number of recent studies published on the impact of modifiable and non-modifiable risk factors on subsequent events after DCIS. The available evidence is insufficient to identify potential targets for risk reduction strategies, reflecting the relatively small numbers and the lack of long-term follow-up in DCIS, a low-event condition.
Need for risk management strategies for untreated DCIS patients. Limited evidence for association between lifestyle factors and prognosis after DCIS. Positive family history, premenopausal status, high breast density associated with prognosis.
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Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A, Cervenka I, Kvaskoff M, Turzanski-Fortner R, Bergmann M, Boeing H, Panico S, Ricceri F, Palli D, Tumino R, Grioni S, José Sánchez Pérez M, Chirlaque MD, Bonet C, Barricarte Gurrea A, Amiano Etxezarreta P, Merino S, Bueno de Mesquita B, van Gils CH, Onland-Moret C, Tjønneland A, Overvad K, Trichopoulou A, Martimianaki G, Karakatsani A, Key T, Chistakoudi S, Ellingjord-Dale M, Tsilidis K, Riboli E, Kaaks R, Gunter MJ, Ferrari P. Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort. Int J Cancer 2020; 146:759-768. [PMID: 30968961 PMCID: PMC6786903 DOI: 10.1002/ijc.32324] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 03/11/2019] [Accepted: 03/13/2019] [Indexed: 12/27/2022]
Abstract
Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
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Affiliation(s)
- Nada Assi
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
| | - Sabina Rinaldi
- Biomarkers Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
| | - Vivian Viallon
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
| | - S. Ghazaleh Dashti
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
- Center for Epidemiology and Biostatistics, The University of Melbourne School of Population and Global Health, Parkville, VIC, Australia
| | - Laure Dossus
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
| | - Agnès Fournier
- CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France
- Gustave Roussy, F-94805, Villejuif, France
- Nutritional Epidemiology Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
| | - Iris Cervenka
- CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France
- Gustave Roussy, F-94805, Villejuif, France
| | - Marina Kvaskoff
- CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France
- Gustave Roussy, F-94805, Villejuif, France
| | | | - Manuela Bergmann
- Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Fulvio Ricceri
- Department of Clinical and Biological Sciences, University of Turin, Italy
- Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, “Civic -M.P.Arezzo” Hospital, ASP Ragusa, Italy
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, 20133, Milan, Italy
| | - María José Sánchez Pérez
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, IBS GRANADA, Universidad de Granada. Granada, Spain
| | - María-Dolores Chirlaque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain
| | - Catalina Bonet
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d’Oncologia, Av. Granvia de L’Hospitalet 199-203, 08908 L’Hospitalet de Llobregat, Spain
| | - Aurelio Barricarte Gurrea
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Navarra Public Health Institute, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA) Pamplona, Spain
| | - Pilar Amiano Etxezarreta
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Public Health Division of Gipuzkoa, BioDonostia Research Institue, San Sebastian, Spain
| | | | - Bas Bueno de Mesquita
- Department. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place W2 1PG London, UK
- Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, 50603, Kuala Lumpur, Malaysia
| | - Carla H. van Gils
- Julius Center for Health Sciences and Primary Care, Cancer Epidemiology University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
| | - Charlotte Onland-Moret
- Julius Center for Health Sciences and Primary Care, Cancer Epidemiology University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
- Department of Public Health, Faculty of Health and Medical Sciences,University of Copenhagen, Denmark
| | - Kim Overvad
- The Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
| | | | | | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece
- Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, Haidari, Greece
| | - Tim Key
- Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
| | - Sofia Chistakoudi
- Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place W2 1PG London, UK
- MRC Centre for Transplantation, King’s College London, Great Maze Pond, London SE1 9RT, United Kingdom
| | - Merete Ellingjord-Dale
- Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place W2 1PG London, UK
| | - Kostas Tsilidis
- Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place W2 1PG London, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place W2 1PG London, UK
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Marc J Gunter
- Nutritional Epidemiology Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
| | - Pietro Ferrari
- Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France
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Lécuyer L, Dalle C, Lefevre-Arbogast S, Micheau P, Lyan B, Rossary A, Demidem A, Petera M, Lagree M, Centeno D, Galan P, Hercberg S, Samieri C, Assi N, Ferrari P, Viallon V, Deschasaux M, Partula V, Srour B, Latino-Martel P, Kesse-Guyot E, Druesne-Pecollo N, Vasson MP, Durand S, Pujos-Guillot E, Manach C, Touvier M. Diet-Related Metabolomic Signature of Long-Term Breast Cancer Risk Using Penalized Regression: An Exploratory Study in the SU.VI.MAX Cohort. Cancer Epidemiol Biomarkers Prev 2020; 29:396-405. [PMID: 31767565 DOI: 10.1158/1055-9965.epi-19-0900] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 10/03/2019] [Accepted: 11/18/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Diet has been recognized as a modifiable risk factor for breast cancer. Highlighting predictive diet-related biomarkers would be of great public health relevance to identify at-risk subjects. The aim of this exploratory study was to select diet-related metabolites discriminating women at higher risk of breast cancer using untargeted metabolomics. METHODS Baseline plasma samples of 200 incident breast cancer cases and matched controls, from a nested case-control study within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, were analyzed by untargeted LC-MS. Diet-related metabolites were identified by partial correlation with dietary exposures, and best predictors of breast cancer risk were then selected by Elastic Net penalized regression. The selection stability was assessed using bootstrap resampling. RESULTS 595 ions were selected as candidate diet-related metabolites. Fourteen of them were selected by Elastic Net regression as breast cancer risk discriminant ions. A lower level of piperine (a compound from pepper) and higher levels of acetyltributylcitrate (an alternative plasticizer to phthalates), pregnene-triol sulfate (a steroid sulfate), and 2-amino-4-cyano butanoic acid (a metabolite linked to microbiota metabolism) were observed in plasma from women who subsequently developed breast cancer. This metabolomic signature was related to several dietary exposures such as a "Western" dietary pattern and higher alcohol and coffee intakes. CONCLUSIONS Our study suggested a diet-related plasma metabolic signature involving exogenous, steroid metabolites, and microbiota-related compounds associated with long-term breast cancer risk that should be confirmed in large-scale independent studies. IMPACT These results could help to identify healthy women at higher risk of breast cancer and improve the understanding of nutrition and health relationship.
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Affiliation(s)
- Lucie Lécuyer
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France.
| | - Céline Dalle
- Clermont Auvergne University, INRA, UMR 1019, Human Nutrition Unit (UNH), CRNH Auvergne, Micronutriments et Santé cardiovasculaire (MicroCard), Clermont-Ferrand, France
- Clermont Auvergne University, INRA, UNH, Plateforme d'Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France
| | - Sophie Lefevre-Arbogast
- University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France
| | - Pierre Micheau
- Clermont Auvergne University, INRA, UMR 1019, Human Nutrition Unit (UNH), CRNH Auvergne, Micronutriments et Santé cardiovasculaire (MicroCard), Clermont-Ferrand, France
| | - Bernard Lyan
- Clermont Auvergne University, INRA, UNH, Plateforme d'Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France
| | - Adrien Rossary
- Clermont Auvergne University, INRA, UMR 1019, Human Nutrition Unit (UNH), CRNH Auvergne, Cellular Micro-Environment, Immunomodulation and Nutrition (ECREIN), Clermont-Ferrand, France
| | - Aicha Demidem
- Clermont Auvergne University, INRA, UMR 1019, Human Nutrition Unit (UNH), CRNH Auvergne, Cellular Micro-Environment, Immunomodulation and Nutrition (ECREIN), Clermont-Ferrand, France
| | - Mélanie Petera
- Clermont Auvergne University, INRA, UNH, Plateforme d'Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France
| | - Marie Lagree
- Clermont Auvergne University, Institut de Chimie de Clermont-Ferrand, Plateforme d'Exploration du Métabolisme, MetaboHUB-Clermont, Aubière, France
| | - Delphine Centeno
- Clermont Auvergne University, INRA, UNH, Plateforme d'Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France
| | - Pilar Galan
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Serge Hercberg
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
- Public Health Department, Avicenne Hospital, Bobigny, France
| | - Cecilia Samieri
- University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France
| | - Nada Assi
- International Agency for Research on Cancer, Section of Nutrition and Metabolism, Nutritional Methodology and Biostatistics Group, Lyon, France
| | - Pietro Ferrari
- International Agency for Research on Cancer, Section of Nutrition and Metabolism, Nutritional Methodology and Biostatistics Group, Lyon, France
| | - Vivian Viallon
- International Agency for Research on Cancer, Section of Nutrition and Metabolism, Nutritional Methodology and Biostatistics Group, Lyon, France
| | - Mélanie Deschasaux
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Valentin Partula
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Bernard Srour
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Paule Latino-Martel
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Emmanuelle Kesse-Guyot
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Nathalie Druesne-Pecollo
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
| | - Marie-Paule Vasson
- Clermont Auvergne University, INRA, UMR 1019, Human Nutrition Unit (UNH), CRNH Auvergne, Cellular Micro-Environment, Immunomodulation and Nutrition (ECREIN), Clermont-Ferrand, France
- Anticancer Center Jean-Perrin, CHU Clermont-Ferrand, France
| | - Stéphanie Durand
- Clermont Auvergne University, INRA, UNH, Plateforme d'Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France
| | - Estelle Pujos-Guillot
- Clermont Auvergne University, INRA, UNH, Plateforme d'Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France
| | - Claudine Manach
- Clermont Auvergne University, INRA, UMR 1019, Human Nutrition Unit (UNH), CRNH Auvergne, Micronutriments et Santé cardiovasculaire (MicroCard), Clermont-Ferrand, France
| | - Mathilde Touvier
- Center of Research of Epidemiology and StatisticS (CRESS), French National Institute of Health and Medical Research (INSERM) U1153, French National Institute for Agricultural Research (INRA) U1125, French National Conservatory of Arts and Crafts (CNAM), Paris 13 University, Nutritional Epidemiology Research Team (EREN), Bobigny, France
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Rainey L, Eriksson M, Trinh T, Czene K, Broeders MJM, van der Waal D, Hall P. The impact of alcohol consumption and physical activity on breast cancer: The role of breast cancer risk. Int J Cancer 2020; 147:931-939. [PMID: 31863475 PMCID: PMC7383781 DOI: 10.1002/ijc.32846] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 11/30/2019] [Accepted: 12/10/2019] [Indexed: 02/01/2023]
Abstract
High alcohol consumption and physical inactivity are known breast cancer risk factors. However, whether the association between these lifestyle factors and breast cancer is modified by a woman's additional breast cancer risk factors has never been studied. Therefore, a population‐based prospective cohort study of 57,654 Swedish women aged 40–74 years, including 957 breast cancer cases, was performed. Alcohol consumption and physical activity were measured with validated web‐based self‐report questionnaires. The Tyrer–Cuzick risk prediction model was used to determine a woman's 10‐year risk of developing breast cancer. Logistic regression models were used to explore whether the effect of alcohol consumption and physical activity on breast cancer was modified by additional breast cancer risk factors. Findings showed that increased alcohol consumption was associated with a higher breast cancer risk (OR = 1.26, 95% CI 1.01, 1.59). However, the association between lifestyle factors (alcohol consumption and physical activity) and breast cancer was generally the same for women at below average, average and above average risk of developing breast cancer. Therefore, additional breast cancer risk factors do not appear to modify the association between lifestyle (alcohol consumption and physical activity) and breast cancer. Considering the general health benefits, preventative lifestyle recommendations can be formulated about alcohol consumption and physical activity for women at all levels of breast cancer risk. What's new? Alcohol consumption and physical inactivity are known breast cancer risk factors but it is currently unclear whether all women would benefit equally from drinking less alcohol and being more physically active. The authors found no difference in association between these lifestyle factors and breast cancer in women with below average, average or above average risk of developing breast cancer. They conclude that general preventative lifestyle recommendations about alcohol intake and physical activity apply to all women regardless of their breast cancer risk.
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Affiliation(s)
- Linda Rainey
- Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mikael Eriksson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Thang Trinh
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Mireille J M Broeders
- Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.,Dutch Expert Centre for Screening, Nijmegen, The Netherlands
| | - Daniëlle van der Waal
- Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Per Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Oncology, Södersjukhuset, Stockholm, Sweden
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Minami Y, Kanemura S, Kawai M, Nishino Y, Tada H, Miyashita M, Ishida T, Kakugawa Y. Alcohol consumption and survival after breast cancer diagnosis in Japanese women: A prospective patient cohort study. PLoS One 2019; 14:e0224797. [PMID: 31721806 PMCID: PMC6853331 DOI: 10.1371/journal.pone.0224797] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 10/10/2019] [Indexed: 01/14/2023] Open
Abstract
Background It is unclear whether alcohol consumption may impact survival after breast cancer diagnosis. To clarify the association between pretreatment alcohol consumption and survival in breast cancer patients, a prospective patient cohort study was conducted. Methods The cohort comprised 1,420 breast cancer patients diagnosed during 1997–2013 at a single institute in Japan. Alcohol drinking and other lifestyle factors were assessed by questionnaire survey at the initial admission. The patients were followed until December 31, 2016. The crude associations of pretreatment alcohol intake with survival were evaluated by Kaplan-Meier analysis. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) controlled by confounders. Results During a median follow-up period of 8.6 years, 261 all-cause and 193 breast cancer-specific deaths were documented. Survival curves showed that ever-drinkers tended to have better survival than never-drinkers (breast cancer-specific survival, log-rank p = 0.0381). Better survival was also observed for light drinkers with an intake of <5.0 g per day. In the Cox model, ever-drinking was associated with a decreased risk of all-cause (HR: 0.75; 95% CI: 0.54–1.05) and breast cancer-specific death (HR: 0.68; 95% CI: 0.46–0.99). Light drinkers had a lower risk of breast cancer-specific death (frequency of drinking, HR = 0.57 for occasional or 1–2 times per week and 0.72 for 3–7 times per week; amount of alcohol consumed per day, HR = 0.57 for <5.0 g and 0.68 for ≥5.0 g compared with never-drinking). In terms of hormone receptor status, a significantly decreased risk of death associated with ever-drinking was observed among women with receptor-negative cancer (ER-/PR-, HR = 0.41; 95% CI: 0.20–0.84 for breast cancer-specific death). Conclusions Pretreatment, i.e., pre-diagnosis alcohol consumption is unlikely to have an adverse effect on survival after breast cancer diagnosis. Light alcohol consumption may have a beneficial effect on patient survival.
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Affiliation(s)
- Yuko Minami
- Division of Community Health, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
- Division of Cancer Epidemiology and Prevention, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan
- Center for Preventive Medicine, Osaki Citizen Hospital, Osaki, Miyagi, Japan
- * E-mail:
| | - Seiki Kanemura
- Division of Cancer Epidemiology and Prevention, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan
| | - Masaaki Kawai
- Department of Breast Surgery, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
| | - Yoshikazu Nishino
- Division of Cancer Epidemiology and Prevention, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan
- Department of Epidemiology and Public Health, Kanazawa Medical University, 1–1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Hiroshi Tada
- Department of Breast Surgery, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
| | - Minoru Miyashita
- Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takanori Ishida
- Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Yoichiro Kakugawa
- Department of Breast Surgery, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
- Department of Surgery, Japanese Red Cross Sendai Hospital, Sendai, Miyagi, Japan
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Alcohol policies and alcohol-attributable cancer mortality in U.S. States. Chem Biol Interact 2019; 315:108885. [PMID: 31678112 DOI: 10.1016/j.cbi.2019.108885] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 10/26/2019] [Indexed: 11/20/2022]
Abstract
BACKGROUND Although more restrictive alcohol control policies (e.g., higher alcohol taxes) are related to lower levels of alcohol consumption, little is known about the relationship between alcohol policies and rates of alcohol-attributable cancer. METHODS State alcohol policy restrictiveness, as measured by a validated policy scale, were related to state rates of six alcohol attributable cancers in the U.S. from 2006 to 2010 in a lagged, cross-sectional linear regression that controlled for a variety of state-level factors. Cancer mortality rates were from the Center for Disease Control and Prevention's Alcohol-Related Disease Impact application, which uses population-attributable fraction methodology to calculate mortality from cancers of the esophagus, larynx, liver, oropharynx, prostate (male only) and breast (female only). RESULTS More restrictive state alcohol policies were associated with lower cancer mortality rates for the six cancer types overall (beta [β] -0.33; 95% confidence interval [CI] -0.59, -0.07), and among men (β -0.45; 95% CI -0.81, -0.10) and women (β -0.21; 95% CI -0.40, -0.02). A 10% increase in the restrictiveness of alcohol policies (based on the mean APS among states) was associated with an 8.5% decrease in rates of combined alcohol-attributable cancers. In all analyses stratified by cancer subtype and sex, the associations were in the hypothesized direction (i.e., more restrictive state policy environments were associated with lower rates of alcohol-attributable cancers), with the exception of laryngeal cancer among women. CONCLUSION Strengthening alcohol policies is a promising prevention strategy for alcohol-related cancer.
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Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, Ruddy K, Tsang J, Cardoso F. Breast cancer. Nat Rev Dis Primers 2019; 5:66. [PMID: 31548545 DOI: 10.1038/s41572-019-0111-2] [Citation(s) in RCA: 1740] [Impact Index Per Article: 290.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/22/2019] [Indexed: 12/24/2022]
Abstract
Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.
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Affiliation(s)
- Nadia Harbeck
- LMU Munich, University Hospital, Department of Obstetrics and Gynecology, Breast Center and Comprehensive Cancer Center (CCLMU), Munich, Germany.
| | - Frédérique Penault-Llorca
- Department of Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre, UMR INSERM 1240, University Clermont Auvergne, Clermont-Ferrand, France
| | - Javier Cortes
- IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Spain.,Vall d´Hebron Institute of Oncology, Barcelona, Spain
| | - Michael Gnant
- Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Nehmat Houssami
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Philip Poortmans
- Department of Radiation Oncology, Institut Curie, Paris, France.,Université PSL, Paris, France
| | - Kathryn Ruddy
- Department of Oncology, Mayo Clinic, Rochester, MN, USA
| | - Janice Tsang
- Hong Kong Breast Oncology Group, The University of Hong Kong, Hong Kong, China
| | - Fatima Cardoso
- Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
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Killelea BK, Gallagher EJ, Feldman SM, Port E, King T, Boolbol SK, Franco R, Fei K, Le Roith D, Bickell NA. The effect of modifiable risk factors on breast cancer aggressiveness among black and white women. Am J Surg 2019; 218:689-694. [PMID: 31375248 DOI: 10.1016/j.amjsurg.2019.07.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 05/22/2019] [Accepted: 07/16/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Although breast cancer incidence is higher among white women, black women are more likely to have aggressive tumors with less favorable histology, and to have a worse prognosis. Obesity and alcohol consumption have been identified as two modifiable risk factors for breast cancer, while physical activity may offer protection. Little however is known about the association of these factors with race on the severity of breast cancer. METHODS Data collected as part of a large prospective study looking at insulin resistance and race among women with breast cancer was queried for patient characteristics, lifestyle factors and tumor characteristics. The association with Nottingham Prognostic Index (NPI) was assessed with different models using univariate and multivariate linear regression. RESULTS Among 746 women in our cohort, 82% (n = 615) were white and 18% (n = 131) were black, mean age 58 years. Black patients were more likely to have high BMI (31.0 vs. 26.7, p < 0.0001), comorbidities (69% vs 55%, p = 0.01), self-reported poor diet (70% vs 42%, p < 0.001), be sedentary (56% vs 46%, p = 0.03) and were less likely to consume alcohol (8% vs 32%, p < 0.0001) compared to white patients. Overall, 137 (18%) of the patients had poorer prognosis (NPI > 4.4), which was significantly associated with younger age (55.6 vs 58.5 years, p = 0.02), black race (27% vs 15%, p = 0.001), triple negative cancer (15% vs 6%, p = 0.003), and poor diet (54% vs 45%, p = 0.046) compared to patients with better prognosis (NPI ≤ 4.4). On multivariate analysis, (model R2 = 0.12; p < 0.001), age (β = -0.011 per year, p = 0.002), healthy diet (β = -0.195, p = 0.02), and exercise (β = -0.004, p = 0.02) were associated with better prognosis, while black race (β = 0.247, p = 0.02) and triple negative cancer (β = 0.908, p < 0.0001) were associated with poor prognosis. Neither alcohol use nor BMI was significantly associated with NPI. CONCLUSION Among modifiable risk factors, diet and exercise are associated with NPI. Unmodifiable factors including race and biologic subtype remain the most important determinants of prognosis.
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Affiliation(s)
- Brigid K Killelea
- 310 Cedar St, LH 118, Yale University School of Medicine, Department of Surgery, New Haven, CT 06510, USA.
| | - Emily J Gallagher
- Icahn School of Medicine at Mt. Sinai, Department of Internal Medicine, New York, NY 10029, USA
| | - Sheldon M Feldman
- Montefiore Medical Center, Department of Surgery, Bronx, NY 10467, USA
| | - Elisa Port
- Icahn School of Medicine at Mt. Sinai, Department of Surgery, New York, NY 10029, USA
| | - Tari King
- Department of Surgery, Harvard Medical School, Boston, MA 02115, USA
| | - Susan K Boolbol
- Icahn School of Medicine at Mt. Sinai, Department of Surgery, New York, NY 10029, USA
| | - Rebeca Franco
- Icahn School of Medicine at Mt. Sinai, Department of Health Evidence and Policy, New York, NY 10029, USA
| | - Kezhen Fei
- Icahn School of Medicine at Mt. Sinai, Department of Health Evidence and Policy, New York, NY 10029, USA
| | - Derek Le Roith
- Icahn School of Medicine at Mt. Sinai, Department of Internal Medicine, New York, NY 10029, USA
| | - Nina A Bickell
- Icahn School of Medicine at Mt. Sinai, Department of Internal Medicine, New York, NY 10029, USA
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Chen S, Yi Y, Xia T, Hong Z, Zhang Y, Shi G, He Z, Zhong S. The influences of red wine in phenotypes of human cancer cells. Gene 2019; 702:194-204. [PMID: 30366081 PMCID: PMC6478559 DOI: 10.1016/j.gene.2018.10.049] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 10/16/2018] [Accepted: 10/19/2018] [Indexed: 02/05/2023]
Abstract
Alcohol intake increases the risk of cancer development. Approximately 3.6% human cancers worldwide derive from chronic alcohol drinking, including oral, liver, breast and other organs. Our studies in vivo and in vitro have demonstrated that diluted ethanol increase RNA Pol III gene transcription and promotes cell proliferation and transformation, as well as tumor formation. However, it is unclear about the effect of red wines on the human cancer cells. In present study, we investigated the roles of red wine in human cancer cell growth, colony formation and RNA Pol III gene transcription. Low concentration (12.5 mM to 25 mM) of ethanol enhances cell proliferation of breast and esophageal cancer lines, whereas its higher concentration (100 mM to 200 mM) slightly decreases the rates. In contrast, red wines significantly repress cell proliferation of different human cancer lines from low dose to high dose. The results reveal that the red wine also inhibits colony formation of human breast cancer and esophageal carcinoma cells. The effects of repression on different human cancer lines are in a dose-dependent manner. Further analysis indicates that ethanol increases RNA Pol III gene transcription, whereas the red wines significantly reduce transcription of the genes. Interestingly, the effects of mature wine (brick red) on cancer cell phenotypes are much stronger than young wine (intense violet). Together, these new findings suggest that red wines may contain some bioactive components, which are able to inhibit human cancer cell growth and colony formation.
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Affiliation(s)
- Songlin Chen
- Department of Cardiothoracic Surgery, Xiamen University Affiliated Southeast Hospital, China
| | - Yunfeng Yi
- Department of Cardiothoracic Surgery, Xiamen University Affiliated Southeast Hospital, China
| | - Ting Xia
- Department of Cardiothoracic Surgery, Xiamen University Affiliated Southeast Hospital, China
| | - Zaifa Hong
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Yanmei Zhang
- Department of Pharmacology, Shantou University Medical College, China; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Ganggang Shi
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China
| | - Zhimin He
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China
| | - Shuping Zhong
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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50
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Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, Chan CW, Choi J, Conroy DM, Dennis J, Dunning AM, Easton DF, Gaborieau V, Gonzalez‐Neira A, Hartman M, Healey CS, Iwasaki M, John EM, Kang D, Kim S, Kwong A, Lophatananon A, Michailidou K, Taib NAM, Muir K, Park SK, Pharoah PDP, Sangrajrang S, Shen C, Shu X, Spinelli JJ, Teo SH, Tessier DC, Tseng C, Tsugane S, Vincent D, Wang Q, Wu AH, Wu P, Zheng W, Matsuo K. The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium. Mol Genet Genomic Med 2019; 7:e707. [PMID: 31066241 PMCID: PMC6565553 DOI: 10.1002/mgg3.707] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 03/21/2019] [Accepted: 04/08/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium. METHODS We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models. RESULTS The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537). CONCLUSION This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.
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Affiliation(s)
- Tomotaka Ugai
- Division of Cancer Epidemiology and Prevention, Department of Preventive MedicineAichi Cancer Center Research InstituteNagoyaJapan
| | - Roger L. Milne
- Cancer Epidemiology & Intelligence DivisionMelbourneVICAustralia
- Centre for Epidemiology and Biostatistics, School of Population and Global HealthThe University of MelbourneMelbourneVICAustralia
| | - Hidemi Ito
- Division of Cancer Information and Control, Department of Preventive MedicineAichi Cancer Center Research InstituteNagoyaJapan
- Department of EpidemiologyNagoya University Graduate School of MedicineNagoyaJapan
| | - Kristan J. Aronson
- Department of Public Health SciencesQueen's Cancer Institute, Queen's UniversityKingstonOntarioCanada
| | - Manjeet K. Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
| | - Tsun Chan
- Hong Kong Hereditary Breast Cancer Family RegistryHappy ValleyHong Kong
- Department of PathologyHong Kong Sanatorium and HospitalHappy ValleyHong Kong
| | - Ching W. Chan
- Department of SurgeryNational University Health SystemSingapore
| | - Ji‐Yeob Choi
- Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
- Cancer Research Institute, Seoul National University College of MedicineSeoulKorea
| | - Don M. Conroy
- Centre for Cancer Genetic Epidemiology, Department of OncologyUniversity of CambridgeCambridgeUK
| | - Joe Dennis
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
| | - Alison M. Dunning
- Centre for Cancer Genetic Epidemiology, Department of OncologyUniversity of CambridgeCambridgeUK
| | - Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
- Centre for Cancer Genetic Epidemiology, Department of OncologyUniversity of CambridgeCambridgeUK
| | - Valerie Gaborieau
- Genetic Epidemiology Group, International Agency for Research on CancerLyonFrance
| | - Anna Gonzalez‐Neira
- Human Cancer Genetics ProgramSpanish National Cancer Research CentreMadridSpain
| | - Mikael Hartman
- Department of SurgeryNational University Health SystemSingapore
- Saw Swee Hock School of Public HealthNational University of SingaporeSingapore
| | - Catherine S. Healey
- Centre for Cancer Genetic Epidemiology, Department of OncologyUniversity of CambridgeCambridgeUK
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Center for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Esther M. John
- Department of Medicine and Stanford Cancer InstituteStanford University School of MedicineStanfordCaliforniaUSA
| | - Daehee Kang
- Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
- Cancer Research Institute, Seoul National University College of MedicineSeoulKorea
- Department of Preventive MedicineSeoul National University College of Medicine, Seoul National UniversitySeoulKorea
| | - Sung‐Won Kim
- Department of SurgeryDaerim Saint Mary's HospitalSeoulKorea
| | - Ava Kwong
- Hong Kong Hereditary Breast Cancer Family RegistryHappy ValleyHong Kong
- Department of SurgeryQueen Mary Hospital, The University of Hong KongHappy ValleyHong Kong
- Department of SurgeryHong Kong Sanatorium and HospitalHappy ValleyHong Kong
| | - Artitaya Lophatananon
- Division of Health Sciences, Warwick Medical SchoolWarwick UniversityCoventryUK
- Division of Population Sciences, Warwick Medical SchoolWarwick UniversityCoventryUK
| | - Kyriaki Michailidou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
- Department of Electron Microscopy/Molecular PathologyThe Cyprus Institute of Neurology and GeneticsNicosiaCyprus
| | - Nur Aishah Mohd Taib
- Breast Cancer Research UnitUniversity Malaya Cancer Research Institute, University Malaya Medical CentreKuala LumpurMalaysia
| | - Kenneth Muir
- Division of Health Sciences, Warwick Medical SchoolWarwick UniversityCoventryUK
- Division of Population Sciences, Warwick Medical SchoolWarwick UniversityCoventryUK
| | - Sue K. Park
- Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
| | - Paul D. P. Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
- Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
| | | | - Chen‐Yang Shen
- Taiwan BiobankInstitute of Biomedical Sciences, Academia SinicaTaipeiTaiwan
- College of Public HealthChina Medical UniversityTaichongTaiwan
| | - Xiao‐Ou Shu
- Division of Epidemiology, Department of MedicineVanderbilt Epidemiology Center, Vanderbilt‐Ingram Cancer Center, Vanderbilt University School of MedicineNashvilleTennesseeUSA
| | - John J. Spinelli
- School of Population & Public HealthUniversity of British ColumbiaVancouverBritish ColumbiaCanada
- Cancer Control Research, BC Cancer AgencyVancouverBritish ColumbiaCanada
| | - Soo H. Teo
- Breast Cancer Research UnitUniversity Malaya Cancer Research Institute, University Malaya Medical CentreKuala LumpurMalaysia
- Cancer Research Initiatives FoundationSime Darby Medical CentreSubang JayaMalaysia
| | - Daniel C. Tessier
- McGill University and Génome Québec Innovation CentreMontrealQuebecCanada
| | - Chiu‐Chen Tseng
- Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Daniel Vincent
- McGill University and Génome Québec Innovation CentreMontrealQuebecCanada
| | - Qin Wang
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
| | - Anna H. Wu
- Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
| | - Pei‐Ei Wu
- Taiwan BiobankInstitute of Biomedical Sciences, Academia SinicaTaipeiTaiwan
| | - Wei Zheng
- Division of Epidemiology, Department of MedicineVanderbilt Epidemiology Center, Vanderbilt‐Ingram Cancer Center, Vanderbilt University School of MedicineNashvilleTennesseeUSA
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Department of Preventive MedicineAichi Cancer Center Research InstituteNagoyaJapan
- Department of EpidemiologyNagoya University Graduate School of MedicineNagoyaJapan
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