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Nagle CM, Ibiebele TI, Na R, Bandera EV, Cramer D, Doherty JA, Giles GG, Goodman MT, Hanley GE, Harris HR, Jensen A, Kjaer SK, Lee A, McGuire V, Milne RL, Qin B, Richardson J, Sasamoto N, Schildkraut JM, Sieh W, Terry KL, Titus L, Trabert B, Wentzensen N, Wu AH, Berchuck A, Pike MC, Pearce CL, Webb PM. Diet and survival after a diagnosis of ovarian cancer: a pooled analysis from the Ovarian Cancer Association Consortium. Am J Clin Nutr 2025; 121:758-768. [PMID: 39921094 PMCID: PMC12002190 DOI: 10.1016/j.ajcnut.2025.02.004] [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: 10/13/2024] [Revised: 01/23/2025] [Accepted: 02/03/2025] [Indexed: 02/10/2025] Open
Abstract
BACKGROUND Prognosis after a diagnosis of invasive epithelial ovarian cancer is poor. Some studies have suggested modifiable behaviors, like diet, are associated with survival but the evidence is inconsistent. OBJECTIVES This study aims to pool data from studies conducted around the world to evaluate the relationships among dietary indices, foods, and nutrients from food sources and survival after a diagnosis of ovarian cancer. METHODS This analysis from the Multidisciplinary Ovarian Cancer Outcomes Group within the Ovarian Cancer Association Consortium included 13 studies with 7700 individuals with ovarian cancer, who completed food-frequency questionnaires regarding their prediagnosis diet. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) for associations with overall survival were estimated using Cox proportional hazards models. RESULTS Overall, there was no association between any of the 7 dietary indices (representing prediagnosis diet) evaluated and survival; however, associations differed by tumor stage. Although there were no consistent associations among those with advanced disease, among those with earlier stage (local/regional) disease, higher scores on the alternate Healthy Eating Index (aHR quartile 4 compared with 1 = 0.66, 95% CI: 0.50, 0.87), Healthy Eating Index-2015 (aHR: 0.75; 95% CI: 0.59, 0.97), and alternate Mediterranean diet (aHR: 0.76; 95% CI: 0.60, 0.98) were associated with better survival. Better survival was also observed for individuals with early-stage disease who reported higher intakes of dietary components that contribute to the healthy diet indices (aHR for Q4 compared with Q1: vegetables 0.71; 95% CI: 0.56, 0.91), tomatoes (aHR: 0.72; 95% CI: 0.57, 0.91) and nuts and seeds (aHR 0.71; 95% CI: 0.55, 0.92). In contrast, there were suggestions of worse survival with higher scores on 2 of the 3 inflammatory indices and higher intake of trans-fatty acids. CONCLUSIONS Adherence to a more healthy, less-inflammatory diet may confer a survival benefit for individuals with early-stage ovarian cancer.
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Affiliation(s)
- Christina M Nagle
- Gynaecological Cancers Group, Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Torukiri I Ibiebele
- Gynaecological Cancers Group, Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Renhua Na
- Gynaecological Cancers Group, Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Elisa V Bandera
- Cancer Prevention and Control Program, Rutgers Cancer Institute, New Brunswick, NJ, United States
| | - Daniel Cramer
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Jennifer A Doherty
- Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, United States
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Marc T Goodman
- Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Community and Population Health Research Institute, Los Angeles, CA, United States
| | - Gillian E Hanley
- Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Holly R Harris
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States
| | - Allan Jensen
- Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark
| | - Susanne K Kjaer
- Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Alice Lee
- Department of Public Health, California State University, Fullerton, Fullerton, CA, United States
| | - Valerie McGuire
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, United States
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Bo Qin
- Cancer Prevention and Control Program, Rutgers Cancer Institute, New Brunswick, NJ, United States
| | - Jean Richardson
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States; Patient advocate
| | - Naoko Sasamoto
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
| | - Joellen M Schildkraut
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Weiva Sieh
- Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Kathryn L Terry
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Linda Titus
- Dartmouth Cancer Center, Lebanon, NH03756, United States
| | - Britton Trabert
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States; Department of Obstetrics and Gynecology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, United States
| | - Nicolas Wentzensen
- Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States
| | - Anna H Wu
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Andrew Berchuck
- Division of Gynecologic Oncology, Duke University School of Medicine, Durham, NC, United States
| | - Malcolm C Pike
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Celeste Leigh Pearce
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, United States
| | - Penelope M Webb
- Gynaecological Cancers Group, Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; University of Queensland, School of Public Health, Brisbane, Queensland, Australia.
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Qin Y, Chen XY, Cao F, Liu JC, Wu L, Liu FH, Li YZ, Xu HL, Wei YF, Huang DH, Li XY, Xiao Q, Gao S, Ma QP, Wang L, Gong TT, Wu QJ. Pre- and post-diagnosis dietary patterns and overall survival in patients with epithelial ovarian cancer: a prospective cohort study. BMC Cancer 2025; 25:363. [PMID: 40016667 PMCID: PMC11869420 DOI: 10.1186/s12885-025-13610-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 01/29/2025] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Previous studies have examined the associations between individual foods or nutrients, but few studies have considered dietary patterns associated with ovarian cancer (OC) survival. METHODS In a prospective cohort study, we examined the association between pre-diagnosis and post-diagnosis overall diet, including changes from pre-diagnosis to post-diagnosis, and overall survival (OS) in 560 patients with OC. Dietary intake was collected using a valid 111-item food frequency questionnaire. Principal component analysis was performed to determine the dietary patterns. Cox proportional hazard regression models were used to assess the hazard ratio (HRs) and 95% confidence interval (CIs). RESULTS Two dietary patterns were identified: Balanced and nutritious pattern and Energy-dense pattern. The highest tertile of the post-diagnosis Balanced and nutritious pattern scores was related to better OS compared with the lowest tertile (HR = 0.40, 95% CI = 0.17-0.95, Ptrend < 0.05). However, no significant association between pre-diagnosis and post-diagnosis Energy-dense pattern scores and OS was observed. Compared to those who had persistently high Balanced and nutritious pattern scores, patients who changed from a high score of pre-diagnosis Balanced and nutritious pattern to low post-diagnosis, as well as those who shifted from a low to a high score, both had a decreased OS (HRhigh-low vs. high-high = 1.91, 95% CI = 1.18-3.08; HRlow-high vs. high-high = 2.19, 95% CI = 1.24-3.86). Additionally, patients who changed from a high pre-diagnosis score to a low post-diagnosis score had a decreased OS compared to those with consistently low Energy-dense pattern scores (HRhigh-low vs. low-low = 1.74, 95% CI = 1.06-2.84). CONCLUSIONS Greater adherence to the Balanced and nutritious pattern as well as less adherence to the Energy-dense pattern from pre-diagnosis to post-diagnosis were associated with better OC survival.
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Affiliation(s)
- Ying Qin
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China
| | - Xi-Yang Chen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China
| | - Fan Cao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Cheng Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Zi Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - He-Li Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dong-Hui Huang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiao-Ying Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qian Xiao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- Medical Insurance Office, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Peng Ma
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Lei Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China.
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
- NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China.
- , Shenyang, China.
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Li Y, Shu J, Tan P, Dong X, Zhang M, He T, Yang Z, Zhang X, Giovannucci EL, Liu Z, Zhou Z, Li Q, Xu Y, Xu X, Peng T, Lu J, Zhang Y, Zhu H, Fang A. Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study. Br J Nutr 2024; 132:1411-1422. [PMID: 39506332 DOI: 10.1017/s0007114524001776] [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] [Indexed: 11/08/2024]
Abstract
Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNP in three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.
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Affiliation(s)
- Yunshan Li
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jing Shu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Peishan Tan
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xiaocong Dong
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Mingjie Zhang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Tongtong He
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zhijun Yang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xuehong Zhang
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Yale University School of Nursing, Orange, CT, USA
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Zhaoyan Liu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zhongguo Zhou
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Qijiong Li
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yanjun Xu
- Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People's Republic of China
| | - Xiaojun Xu
- Department of Chronic Noncommunicable Disease Prevention and Control, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People's Republic of China
| | - Tianyou Peng
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jialin Lu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yaojun Zhang
- Department of Hepatobiliary Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Huilian Zhu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Aiping Fang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
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Na R, Nagle CM, Bartsch S, Ibiebele TI, Williams M, Grant P, Friedlander ML, Webb PM. Use of Dietary Supplements Before, During and After Treatment for Ovarian Cancer: Results from the Ovarian Cancer Prognosis and Lifestyle (OPAL) Study. Nutr Cancer 2024; 77:200-209. [PMID: 39385476 DOI: 10.1080/01635581.2024.2408775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 10/12/2024]
Abstract
The use of dietary supplements by cancer patients is common but contentious, particularly during chemotherapy. Few studies have investigated this for ovarian cancer. In a prospective study of women with ovarian cancer, dietary supplement use was collected through questionnaires. Data on the use of supplements were available for 421 women before diagnosis, during chemotherapy, and after chemotherapy completion. Predictors of changes in supplement use were investigated using logistic regression. The use of ≥1 supplement pre-diagnosis, during, and after chemotherapy completion was reported by 72%, 57%, and 68% of women, respectively. Multivitamins, vitamin D, and fish oils were the most commonly used supplements at all time points. The supplements most commonly discontinued during treatment were fish oils (69% of pre-diagnosis users) and multivitamins (53% of users); while 9%-10% of pre-diagnosis non-users initiated vitamin D and multivitamins. Predictors of supplement initiation during chemotherapy included pre-diagnosis use of medications, such as statins (Odds Ratio, OR = 4.12, 95% confidence interval, CI = 1.28-13.3), antidepressants (5.39, 1.18-24.7), acetaminophen (3.13, 1.05-9.33), and NSAIDs (2.15, 0.81-5.72). Other factors included younger age, university education, neoadjuvant chemotherapy, and/or experiencing fatigue during treatment, although not statistically significant. In conclusion, a high proportion of women with ovarian cancer reported using supplements at all time points.
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Affiliation(s)
- Renhua Na
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
- School of Public Health, University of Queensland, Brisbane, Australia
| | - Christina M Nagle
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Stefanie Bartsch
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Torukiri I Ibiebele
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | | | - Peter Grant
- Gynaecological Oncology Unit, Mercy Hospital for Women, Melbourne, Australia
| | - Michael L Friedlander
- Department of Medical Oncology, Prince of Wales Hospital, and Prince of Wales Clinical School UNSW Sydney, New South Wales, Australia
| | - Penelope M Webb
- Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
- School of Public Health, University of Queensland, Brisbane, Australia
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Sawabe M, Kawakita D, Oze I, Iwasaki S, Hasegawa Y, Murakami S, Ito H, Hanai N, Matsuo K. The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer. Cancers (Basel) 2023; 15:5150. [PMID: 37958324 PMCID: PMC10650771 DOI: 10.3390/cancers15215150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 10/16/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HRT3-T1) = 0.42, 95%CI, 0.25-0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1: 0.83, 95%CI, 0.49-1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.
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Affiliation(s)
- Michi Sawabe
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; (M.S.); (I.O.); (K.M.)
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan;
- Department of Otolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medicine, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan;
| | - Daisuke Kawakita
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; (M.S.); (I.O.); (K.M.)
- Department of Otolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medicine, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan;
| | - Isao Oze
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; (M.S.); (I.O.); (K.M.)
| | - Shinichi Iwasaki
- Department of Otolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medicine, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan;
| | - Yasuhisa Hasegawa
- Department of Head and Neck Surgery, Asahi University Hospital, 3-23 Hashimoto-cho, Gifu 500-8523, Japan;
| | - Shingo Murakami
- Department of Otolaryngology, Head and Neck Surgery, Nagoya City East Medical Center, 1-2-23, Wakamizu, Mizuho-ku, Nagoya 464-8547, Japan;
| | - Hidemi Ito
- Division of Cancer Information and Control, Department of Preventive Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan;
| | - Nobuhiro Hanai
- Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan;
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; (M.S.); (I.O.); (K.M.)
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Liu J, Hong S, Yang J, Zhang X, Wang Y, Wang H, Peng J, Hong L. Targeting purine metabolism in ovarian cancer. J Ovarian Res 2022; 15:93. [PMID: 35964092 PMCID: PMC9375293 DOI: 10.1186/s13048-022-01022-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/17/2022] [Indexed: 11/10/2022] Open
Abstract
Purine, an abundant substrate in organisms, is a critical raw material for cell proliferation and an important factor for immune regulation. The purine de novo pathway and salvage pathway are tightly regulated by multiple enzymes, and dysfunction in these enzymes leads to excessive cell proliferation and immune imbalance that result in tumor progression. Maintaining the homeostasis of purine pools is an effective way to control cell growth and tumor evolution, and exploiting purine metabolism to suppress tumors suggests interesting directions for future research. In this review, we describe the process of purine metabolism and summarize the role and potential therapeutic effects of the major purine-metabolizing enzymes in ovarian cancer, including CD39, CD73, adenosine deaminase, adenylate kinase, hypoxanthine guanine phosphoribosyltransferase, inosine monophosphate dehydrogenase, purine nucleoside phosphorylase, dihydrofolate reductase and 5,10-methylenetetrahydrofolate reductase. Purinergic signaling is also described. We then provide an overview of the application of purine antimetabolites, comprising 6-thioguanine, 6-mercaptopurine, methotrexate, fludarabine and clopidogrel. Finally, we discuss the current challenges and future opportunities for targeting purine metabolism in the treatment-relevant cellular mechanisms of ovarian cancer.
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Affiliation(s)
- Jingchun Liu
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shasha Hong
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiang Yang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiaoyi Zhang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ying Wang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Haoyu Wang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiaxin Peng
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Li Hong
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
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7
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Xu HL, Gong TT, Liu FH, Wei YF, Chen HY, Yan S, Zhao YH, Gao S, Jiao YS, Wu QJ. Pre-diagnosis Dietary One-Carbon Metabolism Micronutrients Consumption and Ovarian Cancer Survival: A Prospective Cohort Study. Front Nutr 2022; 9:873249. [PMID: 35495919 PMCID: PMC9053828 DOI: 10.3389/fnut.2022.873249] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/23/2022] [Indexed: 12/11/2022] Open
Abstract
Background and Aims Epidemiological evidence on the relation between one-carbon metabolism (OCM) micronutrients intake and ovarian cancer (OC) survival are limited and conflicting. We evaluated the aforementioned associations in a prospective cohort-the Ovarian Cancer Follow-Up Study. Methods A total of 635 newly diagnosed OC patients aged 18–79 y were enrolled in the present study. Dietary intake related to one-carbon metabolism, including methionine, vitamins B2, B3, B6, B9, B12, choline, and betaine, was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, via medical records and active follow-up. Cox proportional hazards regression model was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for these aforementioned associations. Results During a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), 114 deaths were identified. We observed an improved survival with the highest compared with the lowest tertile of dietary vitamin B6 (HR = 0.52, 95%CI: 0.32–0.84, P-trend <0.05) and choline intake (HR = 0.50, 95%CI: 0.30–0.83, P-trend <0.05). No significant associations with OC survival were observed for dietary vitamins B2, B3, B9, B12, methionine, and betaine intake. We also observed a curvilinear association between vitamin B6 intake and OC survival (P non-linear <0.05). Conclusion Our study suggests that pre-diagnosis higher intake of vitamin B6 and choline may improve OC survival. Further clarification of these associations is warranted.
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Affiliation(s)
- He-Li Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hong-Yu Chen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shi Yan
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Sheng Jiao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Qi-Jun Wu,
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8
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Yang HJ, Kang Y, Li YZ, Liu FH, Yan S, Gao S, Huo YL, Gong TT, Wu QJ. Relationship between different forms of dietary choline and ovarian cancer survival: findings from the ovarian cancer follow-up study, a prospective cohort study. Food Funct 2022; 13:12342-12352. [DOI: 10.1039/d2fo02594a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Higher levels of pre-diagnosis fat-soluble choline intake was associated with better overall survival of ovarian cancer, and this association was more attributed to phosphatidylcholine.
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Affiliation(s)
- Hui-Juan Yang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ye Kang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Zi Li
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shi Yan
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yun-Long Huo
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
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9
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He TT, Xiao H, Wusiman M, Yishake D, Fang AP, Luo Y, Liu XZ, Liu ZY, Zhu HL. Dietary intake of one-carbon metabolism-related nutrients and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort. Food Funct 2022; 13:8081-8090. [DOI: 10.1039/d2fo00943a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Dietary intake of one-carbon metabolism-related nutrients has been linked to cancer-related outcomes, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. The objective was to assess whether pre-diagnostic...
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10
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Association between pre-diagnostic dietary pattern and survival of ovarian cancer: Evidence from a prospective cohort study. Clin Nutr 2021; 41:452-459. [PMID: 35007814 DOI: 10.1016/j.clnu.2021.12.033] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/19/2021] [Accepted: 12/22/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Evidence for a role of single nutrition or foods on ovarian cancer (OC) survival has been limited and inconclusive. Due to the potentially complex interactions in dietary, we applied dietary patterns to this study to firstly explore the relationship between the pre-diagnosis overall diet and OC survival. METHODS The prospective cohort study was conducted among 853 OC patients aged 18-79 years during 2015-2020. Dietary intake was collected using a validated 111-item food frequency questionnaire. Deaths were obtained by medical records and cancer registry up to March 31, 2021. Cox proportional hazards regression models was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of pre-diagnosis dietary patterns with overall survival (OS). RESULTS Overall, during the follow-up period (median: 37.57 months, interquartile: 25.00-50.17 months), 130 (18.49%) OC patients died. Four dietary patterns were identified: healthy pattern, ethnic pattern, animal foods pattern, and sweet pattern. The highest tertile of the healthy pattern scores was related to better OS compared with the lowest tertile scores (HR = 0.54, 95% CI = 0.30-0.98, p trend <0.05), whereas OC patients with highest adherence to the animal foods pattern was associated with worse OS than those with the lowest adherence (HR = 1.90, 95% CI = 1.14-3.17, p trend <0.05). We found no significant associations between adherence to ethnic pattern and sweet pattern and OS of OC patients. CONCLUSION Pre-diagnosis healthy patterns was associated with better OC survival, whereas animal pattern was associated with worse survival among OC survivals.
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11
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Wei YF, Hao YY, Gao S, Li XQ, Liu FH, Wen ZY, Wang HY, Zhang S, Yan S, Luan M, Zhao YH, Gong TT, Wu QJ. Pre-diagnosis Cruciferous Vegetables and Isothiocyanates Intake and Ovarian Cancer Survival: A Prospective Cohort Study. Front Nutr 2021; 8:778031. [PMID: 34901122 PMCID: PMC8654276 DOI: 10.3389/fnut.2021.778031] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 10/26/2021] [Indexed: 12/14/2022] Open
Abstract
Background: The associations of the consumption of cruciferous vegetables (CVs) and their bioactive components, isothiocyanates (ITCs), with ovarian cancer (OC) mortality have been unclear, owing to limited studies and inconsistent findings. To date, no studies have evaluated these associations among Chinese patients with OC. This study aims to provide more evidence indicating the relationships of pre-diagnosis CVs and ITC intake with OC survival. Methods: We examined the associations of pre-diagnosis CV and ITC intake with OC mortality in a hospital-based cohort (n = 853) of Chinese patients with epithelial OC between 2015 and 2020. Pre-diagnosis dietary information was evaluated with a validated food frequency questionnaire. Deaths were ascertained until March 31, 2021 via medical records and active follow-up. The associations were examined with the Cox proportional hazards model, adjusted for potential confounders, and stratified by menopausal status, residual lesions, histological type, and body mass index (BMI). Results: During a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), we observed 130 deaths. The highest tertile of total CV intake was associated with better survival than the lowest tertile intake [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33–0.98, p trend < 0.05]. In addition, higher intake of ITCs from CVs was associated with better survival (HRT3VS.T1 = 0.59, 95% CI = 0.36–0.99, p trend = 0.06). Significant inverse associations were also observed for subgroup analyses stratified by menopausal status, residual lesions, histological type, and BMI, although not all associations showed statistical significance. Conclusion: Increasing pre-diagnosis consumption of CVs and ITCs was strongly associated with better survival in patients with OC.
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Affiliation(s)
- Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ying-Ying Hao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiu-Qin Li
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhao-Yan Wen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Han-Yuan Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shuang Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shi Yan
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Meng Luan
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China.,Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
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12
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Phillips-Chavez C, Coward J, Watson M, Schloss J. A Retrospective Cross-Sectional Cohort Trial Assessing the Prevalence of MTHFR Polymorphisms and the Influence of Diet on Platinum Resistance in Ovarian Cancer Patients. Cancers (Basel) 2021; 13:5215. [PMID: 34680361 PMCID: PMC8533864 DOI: 10.3390/cancers13205215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/12/2021] [Accepted: 10/14/2021] [Indexed: 11/29/2022] Open
Abstract
Ovarian cancer has the lowest survival rate in gynaecologic malignancies with a 5-year survival rate of 43%. Platinum resistance is one of the main drivers of ovarian cancer mortality, of which aberrant methylation has been cited as a significant contributor. Understanding the essential role of the methylenetetrahydrofolate reductase enzyme (MTHFR) on DNA synthesis and repair, and how nutrient status can vastly affect its performance, led to the investigation of MTHFR status and dietary influence on platinum response in epithelial ovarian cancer (EOC) patients. Twenty-five adult female patients who completed first-line platinum-based chemotherapy for primary ovarian cancer were selected from Icon Cancer Centres in Australia. Participants were grouped based on platinum response. A full medical and family history, food frequency questionnaire and single blood test were completed, testing for MTHFR polymorphisms, serum folate, serum and active B12 and homocysteine levels. Nineteen of twenty-five participants had an MTHFR polymorphism. Of those, 20% were compound heterozygous, 12% were heterozygous C677T (CT), 4% homozygous C677T, 12% homozygous A1298C and 28% were heterozygous A1298C (AC). Statistically significant associations were found between dietary zinc (p = 0.0086; 0.0030; 0.0189) and B12 intakes in CT genotypes (p = 0.0157; 0.0030; 0.0068) indicating that zinc or vitamin B12 intakes below RDI were associated with this genotype. There were strong associations of vitamin B6 intakes in AC genotypes (p = 0.0597; 0.0547; 0.0610), and dietary folate in compound heterozygotes with sensitive and partially sensitive disease (p = 0.0627; 0.0510). There were also significant associations between serum folate (p = 0.0478) and dietary B12 (p = 0.0350) intakes above RDI and platinum sensitivity in wild-types as well as strong associations with homocysteine levels (p = 0.0886) and zinc intake (p = 0.0514). Associations with dietary B12 (p = 0.0514) and zinc intakes (p = 0.0731) were also strong in resistant wild types. Results indicate that dietary zinc, B12 and B6 intakes may be associated with platinum sensitivity dependent on MTHFR genotype. These results require further research to clarify the dosages necessary to elicit a response; however, they provide a novel foundation for acknowledging the role of diet on treatment response in EOC.
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Affiliation(s)
- Caitlin Phillips-Chavez
- Icon Cancer Centre, Queensland, Australia;
- Endeavour College of Natural Health, Brisbane, QLD 4006, Australia;
| | - Jermaine Coward
- Icon Cancer Centre, Queensland, Australia;
- School of Medicine, University of Queensland, Brisbane, QLD 4006, Australia
| | - Michael Watson
- Endeavour College of Natural Health, Brisbane, QLD 4006, Australia;
- Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4006, Australia
| | - Janet Schloss
- NCNM, Southern Cross University, Lismore, NSW 2480, Australia;
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13
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Ben Fradj MK, Ouanes Y, Hadj-Taeib S, Mrad Dali K, Bibi M, Jmal K, Sanhaji H, Nouira Y, Feki M. Prognostic Significance of Plasma Folate and Cobalamin Concentrations in Non-Muscle-Invasive Bladder Cancer: A Prospective Cohort Study. Cancer Invest 2021; 39:240-250. [PMID: 33074725 DOI: 10.1080/07357907.2020.1839760] [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] [Indexed: 10/23/2022]
Abstract
This cohort study aimed to investigate prognostic significance of plasma folate and cobalamin in non-muscle-invasive bladder cancer (NMIBC). A total of 177 NMIBC patients were followed over a period extending to 6 years. Cox regression models were applied to estimate risks for recurrence and progression according to plasma vitamins tertiles. Compared to first tertile, third tertile of plasma folate [HR (95% CI), 10.5 (1.32-83.4); p = 0.026] was associated, and of plasma cobalamin [2.12 (0.63-7.25); p = 0.116] tended to be associated with higher risk for progression. NIMBC patients with high folate/cobalamin statuses should make the physician more alert for a likely poor outcome.
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Affiliation(s)
- Mohamed Kacem Ben Fradj
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia
| | - Yassine Ouanes
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Department of Urology, Rabta Hospital, Tunis, Tunisia
| | - Sameh Hadj-Taeib
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia
| | - Kheireddine Mrad Dali
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Department of Urology, Rabta Hospital, Tunis, Tunisia
| | - Mokhtar Bibi
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Department of Urology, Rabta Hospital, Tunis, Tunisia
| | - Khalil Jmal
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia
| | - Haifa Sanhaji
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia
| | - Yassine Nouira
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Department of Urology, Rabta Hospital, Tunis, Tunisia
| | - Moncef Feki
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia
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14
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Dai W, Liu H, Liu Y, Xu X, Qian D, Luo S, Cho E, Zhu D, Amos CI, Fang S, Lee JE, Li X, Nan H, Li C, Wei Q. Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival. Br J Dermatol 2020; 183:719-728. [PMID: 31955403 PMCID: PMC7367702 DOI: 10.1111/bjd.18878] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVES To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. RESULTS We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10-5 ) and 2·05 (1·39-3·01, P = 2·84 × 10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSIONS Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma.
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Affiliation(s)
- W Dai
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - H Liu
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
| | - Y Liu
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
| | - X Xu
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
| | - D Qian
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
| | - S Luo
- Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA
| | - E Cho
- Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, RI, 02912, USA
- Department of Epidemiology, Brown University School of Public Health, Providence, RI, 02912, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA
| | - D Zhu
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, 77030, USA
| | - C I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, 77030, USA
| | - S Fang
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA
| | - J E Lee
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA
| | - X Li
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA
- Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN, 46202, USA
| | - H Nan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA
- Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN, 46202, USA
| | - C Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Q Wei
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
- Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, 27710, USA
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15
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Liu ZY, Zhang DM, Yishake D, Luo Y, Fang AP, Zhu HL. Dietary choline, rather than betaine intake, is associated with hepatocellular carcinoma mortality. Food Funct 2020; 11:7866-7877. [PMID: 32812611 DOI: 10.1039/d0fo01890b] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The dietary intakes of choline and betaine have been related to the mortality of some neoplasms, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. We examined the associations between dietary choline, five choline-containing compounds, different choline forms, betaine intake and HCC mortality. In total, 905 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort study. Dietary intake was assessed by a valid food frequency questionnaire. Liver cancer-specific mortality (LCSM) and all-cause mortality (ACM) were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox proportional hazards models. It was found that a higher total choline intake was associated with lower ACM, Q4 vs. Q1: HR = 0.72, 95% CI: 0.53-0.97, Ptrend = 0.012 in the fully adjusted model. The associations between total choline intake and LCSM were not significant. Similar associations were found between water-soluble choline intake and HCC mortality, where the fully adjusted HR for ACM was 0.72, 95% CI: 0.53-0.98, Ptrend = 0.017. However, null associations were found between neither phosphatidylcholine (the most abundant lipid-soluble choline) nor total lipid-soluble choline intake and HCC mortality. These results implied that the favorable associations between the total choline intake and ACM were more attributed to water-soluble choline. Furthermore, no significant associations were observed between betaine intake and HCC mortality. Future human intervention trials regarding choline supplementation and liver disease recovery should take the forms into consideration rather than just the total amount alone.
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Affiliation(s)
- Zhao-Yan Liu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
| | - Dao-Ming Zhang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
| | - Dinuerguli Yishake
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
| | - Yun Luo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
| | - Ai-Ping Fang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
| | - Hui-Lian Zhu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
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Phillips-Chavez C, Watson M, Coward J, Schloss J. A systematic literature review assessing if genetic biomarkers are predictors for platinum-based chemotherapy response in ovarian cancer patients. Eur J Clin Pharmacol 2020; 76:1059-1074. [PMID: 32440721 DOI: 10.1007/s00228-020-02874-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 04/06/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Ovarian cancer is the deadliest of gynecologic malignancies with the 5-year overall survival rate remaining at approximately 30%, a rate that has not improved over the last three decades. Standard of care for epithelial ovarian cancer patients consists of a platinum compound with a taxane given intravenously following debulking surgery; however, 80% of cases relapse within 2 years of diagnosis. This review sought to identify key underlying biomarkers related to platinum resistance in ovarian cancer to establish possible prognostic biomarkers of chemoresponse. METHODS A systematic literature review was conducted across three databases PubMed, EMBASE and SCOPUS to summarise the evidence for prognostic biomarkers in platinum-resistant ovarian cancer patients. RESULTS Forty-eight human studies were used in the review encompassing 6719 participants in retrospective and prospective study designs. A total of 68 biomarkers were reported that were significantly correlated with chemoresponse and/or survival reporting a p value less than or equal to 0.05. CONCLUSION This review accentuates the pleiotropic phenotypic complexities related to the response to platinum therapy in ovarian cancer. A one-size-fits-all approach may be ineffective in a large portion of patients, emphasising the need for a whole system-based approach and personalised treatment strategies. Identifying key biomarkers to aid clinical decision-making is the first essential step in developing and appropriating therapies for at-risk patients, reducing toxicity and improving quality of life.
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Affiliation(s)
- Caitlin Phillips-Chavez
- Icon Cancer Centre, Southport, Australia.
- Endeavour College of Natural Health, 105 Scarborough Street, Southport, QLD, 4215, Australia.
| | - Michael Watson
- Endeavour College of Natural Health, 105 Scarborough Street, Southport, QLD, 4215, Australia
| | - Jermaine Coward
- Icon Cancer Centre, South Brisbane, Australia
- School of Medicine, University of Queensland, Brisbane, Australia
| | - Janet Schloss
- Endeavour College of Natural Health, Level 2, 269 Wickham Street, Fortitude Valley, Brisbane, QLD, 4006, Australia
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17
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Liu ZY, Yishake D, Fang AP, Zhang DM, Liao GC, Tan XY, Zhang YJ, Zhu HL. Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study. Nutr Metab (Lond) 2020; 17:25. [PMID: 32256673 PMCID: PMC7106561 DOI: 10.1186/s12986-020-00445-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 03/21/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Higher choline and betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival. METHODS 866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS Serum choline levels were associated with better LCSS (T3 vs. T1: HR = 0.69, 95% CI: 0.51-0.94; P -trend < 0.05) and OS (T3 vs. T1: HR = 0.73, 95% CI: 0.54-0.99; P -trend < 0.05). The associations were significantly modified by C-reactive protein (CRP) levels but not by other selected prognostic factors including sex, age, etc. The favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS. CONCLUSIONS This study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our findings suggest the benefits of choline on HCC survival. TRIAL REGISTRATION The Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT03297255.
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Affiliation(s)
- Zhao-Yan Liu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
| | - Dinuerguli Yishake
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
| | - Ai-Ping Fang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
| | - Dao-Ming Zhang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
| | - Gong-Cheng Liao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
| | - Xu-Ying Tan
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060 People’s Republic of China
| | - Hui-Lian Zhu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080 People’s Republic of China
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18
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Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study. Br J Nutr 2019; 121:1376-1388. [DOI: 10.1017/s0007114519000734] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AbstractExisting data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
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19
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Assis J, Pereira C, Nogueira A, Pereira D, Carreira R, Medeiros R. Genetic variants as ovarian cancer first-line treatment hallmarks: A systematic review and meta-analysis. Cancer Treat Rev 2017; 61:35-52. [PMID: 29100168 DOI: 10.1016/j.ctrv.2017.10.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 10/02/2017] [Accepted: 10/07/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research. METHODS A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016. Studies were pooled and summary estimates and 95% confidence intervals (CI) were calculated using random or fixed-effects models as appropriate. RESULTS One hundred and forty-two studies gathering 106871 patients were included. Combined data suggested that GSTM1-null genotype patients have a lower risk of death compared to GSTM1-wt carriers, specifically in advanced stages (hazard ratio (HR), 0.68; 95% CI, 0.48-0.97) and when submitted to platinum-based chemotherapy (aHR, 0.61; 95% CI, 0.39-0.94). ERCC1 rs11615 and rs3212886 might have also a significant impact in treatment outcome (aHR, 0.67; 95% CI, 0.51-0.89; aHR, 1.28; 95% CI, 1.01-1.63, respectively). Moreover, ERCC2 rs13181 and rs1799793 showed a distinct ethnic behavior (Asians: aHR, 1.41; 95% CI, 0.80-2.49; aHR, 1.07; 95% CI, 0.62-1.86; Caucasians: aHR, 0.10; 95% CI, 0.01-0.96; aHR, 0.18; 95% CI, 0.05-0.68, respectively). CONCLUSION(S) The definition of integrative predictive models should encompass genetic information, especially regarding GSTM1 homozygous deletion. Justifying additional pharmacogenetic investigation are variants in ERCC1 and ERCC2, which highlight the DNA Repair ability to ovarian cancer prognosis. Further knowledge could aid to understand platinum-treatment failure and to tailor chemotherapy strategies.
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Affiliation(s)
- Joana Assis
- Molecular Oncology and Viral Pathology Group - Research Center, Portuguese Institute of Oncology, Porto, Portugal; FMUP, Faculty of Medicine of Porto University, Porto, Portugal
| | - Carina Pereira
- Molecular Oncology and Viral Pathology Group - Research Center, Portuguese Institute of Oncology, Porto, Portugal; CINTESIS, Center for Health Technology and Services Research, FMUP, Porto, Portugal
| | - Augusto Nogueira
- Molecular Oncology and Viral Pathology Group - Research Center, Portuguese Institute of Oncology, Porto, Portugal; FMUP, Faculty of Medicine of Porto University, Porto, Portugal
| | - Deolinda Pereira
- Oncology Department, Portuguese Institute of Oncology, Porto, Portugal
| | - Rafael Carreira
- Centre of Biological Engineering, University of Minho, Braga, Portugal; SilicoLife, Lda, Braga, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group - Research Center, Portuguese Institute of Oncology, Porto, Portugal; Research Department, Portuguese League Against Cancer (NRNorte), Porto, Portugal; CEBIMED, Faculty of Health Sciences of Fernando Pessoa University, Porto, Portugal.
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20
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Playdon MC, Nagle CM, Ibiebele TI, Ferrucci LM, Protani MM, Carter J, Hyde SE, Neesham D, Nicklin JL, Mayne ST, Webb PM. Pre-diagnosis diet and survival after a diagnosis of ovarian cancer. Br J Cancer 2017; 116:1627-1637. [PMID: 28463959 PMCID: PMC5518850 DOI: 10.1038/bjc.2017.120] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 04/05/2017] [Accepted: 04/06/2017] [Indexed: 12/12/2022] Open
Abstract
Background: The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings. Methods: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake. Results: We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53–0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62–0.99), fish (HR=0.74, 95% CI: 0.57–0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59–0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01–1.65, P-trend=0.03). Conclusions: The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.
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Affiliation(s)
- Mary C Playdon
- Yale School of Public Health, Department of Chronic Disease Epidemiology, Yale University, 60 College Street, New Haven, CT 06520, USA
| | - Christina M Nagle
- Gynaecological Cancers Group, QIMR Berghofer Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia
| | - Torukiri I Ibiebele
- Gynaecological Cancers Group, QIMR Berghofer Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia
| | - Leah M Ferrucci
- Yale School of Public Health, Department of Chronic Disease Epidemiology, Yale University, 60 College Street, New Haven, CT 06520, USA
| | - Melinda M Protani
- Gynaecological Cancers Group, QIMR Berghofer Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia.,School of Public Health, University of Queensland Public Health Building, Herston Road, Queensland 4006, Australia
| | - Jonathan Carter
- Department of Gynaecological Oncology, The University of Sydney, Sydney, New South Wales 2006, Australia.,Lifehouse Gynaecologic Oncology Group, Lifehouse, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia
| | - Simon E Hyde
- Mercy Hospital for Women, Department of Gynaecological Oncology, Studley Road, Heidelberg, Victoria 3084, Australia
| | - Deborah Neesham
- Oncology/Dysplasia Unit, The Royal Women's Hospital, Flemington Road, Parkville, Victoria 3052, Australia
| | - James L Nicklin
- Queensland Centre for Gynaecological Cancer, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Queensland 4029, Australia.,School of Medicine, Department of Obstetrics and Gynaecology, The University of Queensland, Herston, Queensland 4006, Australia
| | - Susan T Mayne
- Yale School of Public Health, Department of Chronic Disease Epidemiology, Yale University, 60 College Street, New Haven, CT 06520, USA.,Yale Cancer Center, New Haven, CT 06520, USA.,U.S. Food and Drug Administration, College Park, MD, USA
| | - Penelope M Webb
- Gynaecological Cancers Group, QIMR Berghofer Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia.,School of Public Health, University of Queensland Public Health Building, Herston Road, Queensland 4006, Australia
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21
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Poole EM, Konstantinopoulos PA, Terry KL. Prognostic implications of reproductive and lifestyle factors in ovarian cancer. Gynecol Oncol 2016; 142:574-87. [DOI: 10.1016/j.ygyno.2016.05.014] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 05/10/2016] [Accepted: 05/12/2016] [Indexed: 10/21/2022]
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22
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Chan YM, MacFarlane AJ, O'Connor DL. Modeling Demonstrates That Folic Acid Fortification of Whole-Wheat Flour Could Reduce the Prevalence of Folate Inadequacy in Canadian Whole-Wheat Consumers. J Nutr 2015; 145:2622-9. [PMID: 26423740 DOI: 10.3945/jn.115.217851] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 09/02/2015] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Mandatory folic acid fortification of white-wheat flour and selected other grain products has reduced the prevalence of neural tube defects in Canada; however, the fortification of whole-wheat flour is not permitted. OBJECTIVE The objective of this study was to model the impact of adding folic acid to whole-wheat flour on the folate intake distribution of Canadians. METHODS Twenty-four-hour dietary recall and supplement intake data (n = 35,107) collected in the 2004 Canadian Community Health Survey 2.2 were used to calculate the prevalence of folate inadequacy (POFI) and the proportion of folic acid intakes above the Tolerable Upper Intake Level (UL). In model 1, folic acid was added to whole-wheat flour-containing foods in amounts comparable to those that are mandatory for white-wheat flour-containing foods. In model 2, a 50% overage of folic acid fortification was considered. Models 3 and 4 included assessment of folate intake distributions in adult whole-wheat consumers with or without a fortification overage. SIDE (Software for Intake Distribution Estimation; Department of Statistics and Center for Agricultural and Rural Development, Iowa State University) was used to estimate usual folate intakes. RESULTS Mean folate intakes increased by ∼ 5% in all sex and age groups when whole-wheat foods were fortified (models 1 and 2; P < 0.0001). Folic acid fortification of whole-wheat flour-containing foods did not change the POFI or percentage of intakes above the UL in the general population, whether in supplement users or nonusers. Among whole-wheat consumers, the POFI was reduced by 10 percentage points after fortification of whole-wheat flour-containing foods (95% CIs did not overlap). The percentage of whole-wheat consumers with intakes above the UL did not change. CONCLUSION Although folic acid fortification of whole-wheat flour-containing foods is unlikely to change the POFI or proportion of folic acid intakes above the UL in the general Canadian population, this fortification strategy may reduce the POFI in adult whole-wheat consumers.
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Affiliation(s)
- Yen-Ming Chan
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; and
| | | | - Deborah L O'Connor
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; and
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Shorter KR, Felder MR, Vrana PB. Consequences of dietary methyl donor supplements: Is more always better? PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2015; 118:14-20. [PMID: 25841986 DOI: 10.1016/j.pbiomolbio.2015.03.007] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 03/11/2015] [Accepted: 03/13/2015] [Indexed: 11/16/2022]
Abstract
Epigenetic mechanisms are now recognized to play roles in disease etiology. Several diseases increasing in frequency are associated with altered DNA methylation. DNA methylation is accomplished through metabolism of methyl donors such as folate, vitamin B12, methionine, betaine (trimethylglycine), and choline. Increased intake of these compounds correlates with decreased neural tube defects, although this mechanism is not well understood. Consumption of these methyl donor pathway components has increased in recent years due to fortification of grains and high supplemental levels of these compounds (e.g. vitamins, energy drinks). Additionally, people with mutations in one of the enzymes that assists in the methyl donor pathway (5-MTHFR) are directed to consume higher amounts of methyl donors to compensate. Recent evidence suggests that high levels of methyl donor intake may also have detrimental effects. Individualized medicine may be necessary to determine the appropriate amounts of methyl donors to be consumed, particularly in women of child bearing age.
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Affiliation(s)
- Kimberly R Shorter
- University of Florida School of Medicine, Department of Psychiatry at the McKnight Brain Institute, 1149 Newell Drive, Gainesville, FL 32611, USA
| | - Michael R Felder
- University of South Carolina, Department of Biological Sciences, 715 Sumter Street, Columbia, SC 29208, USA; Peromyscus Genetic Stock Center, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA
| | - Paul B Vrana
- University of South Carolina, Department of Biological Sciences, 715 Sumter Street, Columbia, SC 29208, USA; Peromyscus Genetic Stock Center, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA.
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Aragón F, Perdigón G, LeBlanc ADMD. Modification in the diet can induce beneficial effects against breast cancer. World J Clin Oncol 2014; 5:455-464. [PMID: 25114859 PMCID: PMC4127615 DOI: 10.5306/wjco.v5.i3.455] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 05/15/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
The population tends to consume foods that in addition to their nutritional values can offer some benefits to their health. There are many epidemiological evidences and research studies in animal models suggesting that diet plays an important role in breast cancer prevention or progression. This review summarized some of the relevant researches about nutrition and cancer during the last years, especially in breast cancer. The analysis of probiotics and fermented products containing lactic acid bacteria in cancer prevention and/or treatment was especially discussed. It was observed that a balance of fatty acids similar to those of traditional Mediterranean diet, the consumption of fruits and vegetables, dietary fiber intake, vitamin supplementation are, along with the intake of probiotic products, the most extensively studied by the negative association to breast cancer risk. The consumption of probiotics and fermented products containing lactic acid bacteria was associated to reduce breast cancer risk in some epidemiological studies. The use of animal models showed the modulation of the host’s immune response as one of the important effects associated to the benefices observed with most probiotics. However; future assays in human are very important before the medical community can accept the addition of probiotic or fermented milks containing lactic acid bacteria as supplements for cancer patients.
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