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Cheng WM, Li PC, Nguyen MTB, Lin YT, Huang YT, Cheng TS, Nguyen TH, Tran TH, Huang TY, Hoang TH, Chen SY, Chu YC, Wu CW, Lee MF, Chiou YS, Liu HS, Hong YR, Chang PMH, Hu YF, Chang YC, Lai JM, Huang CYF. Repurposing pitavastatin and atorvastatin to overcome chemoresistance of metastatic colorectal cancer under high glucose conditions. Cancer Cell Int 2025; 25:79. [PMID: 40050889 PMCID: PMC11887183 DOI: 10.1186/s12935-025-03712-2] [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: 04/04/2024] [Accepted: 02/22/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) poses a significant clinical challenge because of drug resistance, which can adversely impact patient outcomes. Recent research has shown that abnormalities within the tumor microenvironment, especially hyperglycemia, play a crucial role in promoting metastasis and chemoresistance, and thereby determine the overall prognosis of patients with advanced CRC. METHODS This study employs data mining and consensus molecular subtype (CMS) techniques to identify pitavastatin and atorvastatin as potential agents for targeting high glucose-induced drug resistance in advanced CRC cells. CRC cells maintained under either low or high glucose conditions were established and utilized to assess the cytotoxic effects of pitavastatin and atorvastatin, both with and without 5-fluorouracil (5-FU). CRC 3D spheroids cultured were also included to demonstrate the anti-drug resistance of pitavastatin and atorvastatin. RESULTS A bioinformatics analysis identified pitavastatin and atorvastatin as promising drug candidates. The CMS4 CRC cell line SW480 (SW480-HG) was established and cultured under high glucose conditions to simulate hyperglycemia-induced drug resistance and metastasis in CRC patients. Pitavastatin and atorvastatin could inhibit cell proliferation and 3D spheroid formation of CMS4 CRC cells under high glucose conditions. In addition, both pitavastatin and atorvastatin can synergistically promote the 5-FU-mediated cytotoxic effect and inhibit the growth of 5-FU-resistant CRC cells. Mechanistically, pitavastatin and atorvastatin can induce apoptosis and synergistically promote the 5-FU-mediated cytotoxic effect by activating autophagy, as well as the PERK/ATF4/CHOP signaling pathway while decreasing YAP expression. CONCLUSION This study highlights the biomarker-guided precision medicine strategy for drug repurposing. Pitavastatin and atorvastatin could be used to assist in the treatment of advanced CRC, particularly with CMS4 subtype CRC patients who also suffer from hyperglycemia. Pitavastatin, with an achievable dosage used for clinical interventions, is highly recommended for a novel CRC therapeutic strategy.
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Affiliation(s)
- Wei-Ming Cheng
- Program in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Department of Urology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Division of Urology, Department of Surgery, Zhongxiao Branch, Taipei City Hospital, Taipei, 115, Taiwan
| | - Po-Chen Li
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Minh Tran-Binh Nguyen
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
| | - Yu-Teng Lin
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Yu-Tang Huang
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Tai-Shan Cheng
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Department of Orthopedic Surgery, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan
| | - Thi-Huong Nguyen
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Institute of Biotechnology and Food Technology, Thai Nguyen University of Agriculture and Forestry, Thai Nguyen, Vietnam
| | - Thu-Ha Tran
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, 112, Taiwan
| | - Tzu-Yi Huang
- Program in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Thu-Huyen Hoang
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Sin-Yu Chen
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Yu-Chieh Chu
- Taipei First Girls High School, Taipei, 110, Taiwan
| | - Chih-Wei Wu
- Taipei First Girls High School, Taipei, 110, Taiwan
| | - Ming-Fen Lee
- Department of Nutrition, China Medical University, Taichung, 406, Taiwan
| | - Yi-Shiou Chiou
- Master Degree Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Hsiao-Sheng Liu
- Medical Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- 13 M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- Center for Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung City, 807, Taiwan
| | - Yi-Ren Hong
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
- Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan
| | - Peter Mu-Hsin Chang
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Department of Oncology, Taipei Veterans General Hospital, Taipei, 112, Taiwan
| | - Yu-Feng Hu
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
- Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan
- Institute of Biomedical Sciences, Academia Sinica, 115, Taipei, Taiwan
| | - Ying-Chih Chang
- Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan
- Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA
| | - Jin-Mei Lai
- Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City, 242, Taiwan.
| | - Chi-Ying F Huang
- Program in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.
- Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
- Chong Hin Loon Memorial Cancer and Biotherapy Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.
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Xia D, Jin L, Wang B, Jin Y, Zheng Q, Xu J, Chen S. Alpha-glucosidase inhibitor decreases the risk of colorectal adenoma in the aged with Type 2 diabetes. Sci Rep 2025; 15:583. [PMID: 39748054 PMCID: PMC11696837 DOI: 10.1038/s41598-024-84294-3] [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: 07/27/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025] Open
Abstract
The rapidly aging population is fueling a surge in diabetes, especially Type 2, which heightens colorectal cancer (CRC) risk. Colorectal adenoma, a precursor, compounds this trend. Although alpha-glucosidase inhibitors are effective hypoglycemic drugs working in the GI tract, the link between them and colorectal adenoma formation remains unexplored. A retrospective cross-sectional study was conducted on type 2 diabetes patients aged 60 and above using data from Wenzhou Central Hospital from January 2021 to May 2024. We used multivariable logistic regression and propensity score matching analysis (PSM) to calculate adjusted ORs for colorectal adenoma, controlling for potential confounders. A total of 311 subjects were enrolled in the study, with a mean age of 67.55 years. 138 (44.4%) were diagnosed with colorectal adenoma. Multivariate logistic regression analysis revealed that the AGI (Alpha-glucosidase inhibitor) Group had an adjusted OR of 0.399 (95% CI = 0.22-0.723, p = 0.002) compared to those with AGI free people. A similar trend was also observed in the PSM analysis (OR = 0.362, 95% CI = 0.176-0.744, p = 0.004). Subgroup analysis reveals hypertension as a potential modulator of the inverse relationship between AGI and colorectal adenoma occurrence post-PSM (p = 0.049). And AGI reduces serum iron levels, both before (p = 0.01) and after PSM (p = 0.028). In summary, our findings indicate that AGI significantly mitigates the risk of colorectal adenoma among individuals aged 60 and above, particularly among those afflicted with hypertension. Additionally, it substantially decreases serum iron levels.
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Affiliation(s)
- Dingchao Xia
- Department of Infectious Diseases, Wenzhou Central Hospital, Wenzhou, 325000, Zhejiang, China
- Department of Infectious Diseases, Wenzhou Sixth People's Hospital, Wenzhou, 325000, Zhejiang, China
| | - Lanling Jin
- Department of Neurology, Pujiang County People's Hospital, Wenzhou, Jinhua, 322200, Zhejiang, China
| | - Binfeng Wang
- Department of Gastroenterology, Affiliated Yueqing Hospital,Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Yi Jin
- Department of Rheumatology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Qun Zheng
- Department of Rheumatology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Jie Xu
- Department of Rheumatology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
| | - Senzhong Chen
- Department of Gerontology, Wenzhou Central Hospital, Wenzhou, 325000, Zhejiang, China.
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Ning W, Liu J, Lu Y, Zhu B, Zhang WH, Mao Y. Trends in the Disease Burden and Risk Factors of Women's Cancers in China From 1990 to 2019. Int J Public Health 2024; 69:1607245. [PMID: 39698306 PMCID: PMC11652174 DOI: 10.3389/ijph.2024.1607245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 11/22/2024] [Indexed: 12/20/2024] Open
Abstract
Objectives To examine age-specific trends and risk factors in the burden of women's cancers (WCs) in China from 1990 to 2019 to inform strategies. Methods Data were sourced from the Global Burden of Disease 2019 and World Population Prospects 2019. Time trends, age differences, and key factors for breast, cervical, and ovarian cancers (BC, CC, and OC) were analyzed based on age-standardized incidence rate (ASIR) and disability-adjusted life years (DALYs) rate. Results ASIRs for BC and CC increased over the study period, with a slower growth rate for CC after 2005, likely due to targeted HPV prevention. OC showed the highest ASIR and DALY increases, indicating a growing concern. Peak ASIR for BC and CC was in women aged 50-55, while OC showed a higher burden in women aged 70-79. Lower DALYs in women born after 1985 suggest improved healthcare access. Conclusion This study highlights significant trends in cancer burden among Chinese women, driven by age and reproductive health policies. Future efforts should enhance screening, health literacy, and age-targeted risk reduction for specific cancer types.
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Affiliation(s)
- Wei Ning
- School of Public Policy and Administration, Xi’an Jiaotong University, Xi’an, China
- International Centre for Reproductive Health, Ghent University, Ghent, Belgium
| | - Jinnan Liu
- School of Public Policy and Administration, Xi’an Jiaotong University, Xi’an, China
| | - Yongbo Lu
- School of Public Policy and Administration, Xi’an Jiaotong University, Xi’an, China
| | - Bin Zhu
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
| | - Wei-Hong Zhang
- International Centre for Reproductive Health, Ghent University, Ghent, Belgium
| | - Ying Mao
- School of Public Policy and Administration, Xi’an Jiaotong University, Xi’an, China
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Molla MD, Symonds EL, Winter JM, Debie A, Wassie MM. Metabolic risk factors of colorectal cancer: Umbrella review. Crit Rev Oncol Hematol 2024; 204:104502. [PMID: 39245299 DOI: 10.1016/j.critrevonc.2024.104502] [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: 07/26/2024] [Revised: 08/28/2024] [Accepted: 08/29/2024] [Indexed: 09/10/2024] Open
Abstract
BACKGROUND AND AIM The association between metabolic factors and colorectal cancer (CRC) risk is inconclusive. This umbrella review aimed to summarise and describe the association using existing systematic reviews and/or meta-analyses. METHOD Four databases (Medline, Scopus, Web of Science, and Cochrane Library) were searched for systematic reviews and/or meta-analyses of observational studies. Two independent authors extracted data on the summary estimated effect and heterogeneity of studies using I2 from the individual reviews. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) tool was used to evaluate the methodological quality. RESULTS 49 articles were included in this review. Although most included studies were graded with critically low methodological quality (81.6 %), we found a significant positive association between obesity (summary relative risk (SRR) range 1.19-1.49), diabetes mellitus (SRR range 1.20-1.37), hypertension (SRR range 1.07-1.62), metabolic syndrome (SRR range 1.25-1.36), non-alcoholic fatty liver disease (pooled odds ratio (POR) range 1.13-1.56), and risk of CRC. Higher serum high-density lipoprotein cholesterol levels were associated with a lower risk of CRC in 3/6 reviews, while others did not find any association. There was no clear association between high triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol levels, and risk of CRC. CONCLUSION This umbrella review identified that most metabolic factors are significantly associated with increased risk of CRC. Thus, people affected by metabolic factors may be benefited from CRC screening and surveillance.
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Affiliation(s)
- Meseret Derbew Molla
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Biochemistry, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Erin L Symonds
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia; Gastroenterology and Hepatology Department, Flinders Medical Centre, Southern Adelaide Local Health Network, Bedford Park, South Australia, Australia
| | - Jean M Winter
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Ayal Debie
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Health Systems and Policy, Institute of Public Health, University of Gondar, Gondar, Ethiopia
| | - Molla M Wassie
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia
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Fernández-Arce L, Robles-Rodríguez N, Fernández-Feito A, Fernández-Iglesias R, Fernández-Álvarez MDM, Lana A. Impact of Breast Cancer on Cardiometabolic Health in Spanish Women ≥50 Years with Pre-Existing Type 2 Diabetes Mellitus. Cancers (Basel) 2024; 16:2853. [PMID: 39199624 PMCID: PMC11352853 DOI: 10.3390/cancers16162853] [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: 07/01/2024] [Revised: 08/03/2024] [Accepted: 08/13/2024] [Indexed: 09/01/2024] Open
Abstract
During breast cancer (BC), cardiometabolic disorders can worsen prognosis, particularly in women with type 2 diabetes mellitus (T2DM). This study aimed to determine the impact of BC diagnosis on cardiometabolic parameters and the incidence of complication in women over 50 years of age (90% aged ≥ 65 years) with pre-existing T2DM. Using primary care registries from Asturias (Spain), a total of 106 women diagnosed with T2DM followed by BC were selected and matched with women with T2DM (n = 212) in a cohort study. Indicators of cardiometabolic health and microvascular complications associated with T2DM were collected. Women were monitored from two years prior to five years after BC diagnosis. Conditional logistic regressions were used to compare the adjusted odds of staying below each indicator's threshold. During follow-up, women with T2DM+BC had a higher risk of fasting blood glucose ≥126 mg/dL (adjusted odds ratio [aOR] = 1.83; 95% confidence interval [CI95%]: 1.01-3.32) and glycosylated hemoglobin (Hb1Ac) ≥ 48 mmol/mol or 6.5% (aOR: 2.44; IC95%: 1.21-4.91). There was no difference between the groups regarding the incidence of microvascular complications. BC incidence negatively impacted the glycemic control of Spanish women with pre-existing T2DM measured by basal blood glucose and HbA1c, but not cardiometabolic health indicators or T2DM complications.
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Affiliation(s)
- Lucía Fernández-Arce
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Oviedo/ISPA, 33006 Oviedo, Spain; (N.R.-R.); (A.F.-F.); (R.F.-I.); (A.L.)
| | - Nena Robles-Rodríguez
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Oviedo/ISPA, 33006 Oviedo, Spain; (N.R.-R.); (A.F.-F.); (R.F.-I.); (A.L.)
| | - Ana Fernández-Feito
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Oviedo/ISPA, 33006 Oviedo, Spain; (N.R.-R.); (A.F.-F.); (R.F.-I.); (A.L.)
| | - Rocío Fernández-Iglesias
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Oviedo/ISPA, 33006 Oviedo, Spain; (N.R.-R.); (A.F.-F.); (R.F.-I.); (A.L.)
| | - María del Mar Fernández-Álvarez
- Department of Surgery and Medical Surgical Specialities, Faculty of Medicine and Health Sciences, University of Oviedo/ISPA, 33006 Oviedo, Spain;
| | - Alberto Lana
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Oviedo/ISPA, 33006 Oviedo, Spain; (N.R.-R.); (A.F.-F.); (R.F.-I.); (A.L.)
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Li M, Zhang L, Guan T, Huang L, Zhu Y, Wen Y, Ma X, Yang X, Wan R, Chen J, Zhang C, Wang F, Tang H, Liu T. Energy stress-activated AMPK phosphorylates Snail1 and suppresses its stability and oncogenic function. Cancer Lett 2024; 595:216987. [PMID: 38815798 DOI: 10.1016/j.canlet.2024.216987] [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: 02/01/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/01/2024]
Abstract
Triple-negative breast cancer (TNBC) is a highly lethal malignancy with limited therapy options. Aberrant metabolism, a key hallmark of human cancers, plays a crucial role in tumor progression, therapeutic responses and TNBC-related death. However, the underlying mechanisms are not fully understood. In this study, we delineate a previously unrecognized role of aberrant glucose metabolism in regulating the turnover of Snail1, which is a key transcriptional factor of epithelial-mesenchymal transition (EMT) and critically contributes to the acquisition of stemness, metastasis and chemo-resistance. Mechanistically, we demonstrate that AMP-activated protein kinase (AMPK), when activated in response to glucose deprivation, directly phosphorylates Snail1 at Ser11. Such a phosphorylation modification of Snail1 facilitates its recruitment of the E3 ligase FBXO11 and promotes its degradation, thereby suppressing stemness, metastasis and increasing cellular sensitivity to chemotherapies in vitro and in vivo. Clinically, histological analyses reveal a negative correlation between p-AMPKα and Snail1 in TNBC specimens. Taken together, our findings establish a novel mechanism and functional significance of AMPK in linking glucose status to Snail1-dependent malignancies and underscore the potential of AMPK agonists as a promising therapeutic strategy in the management of TNBC.
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Affiliation(s)
- Mei Li
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Litao Zhang
- Department of Breast Surgery, The First Affiliate Hospital of Jinan University, Guangzhou, 510632, China
| | - Tangming Guan
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Lei Huang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Yingjie Zhu
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Yalei Wen
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Xiuqing Ma
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Xiao Yang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Rui Wan
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Jiayi Chen
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Caishi Zhang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China
| | - Feng Wang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China.
| | - Hui Tang
- Department of Central Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China; Department of Clinical Laboratory, The Fifth Affiliated Hospital of Jinan University Heyuan Shenhe People's Hospital, Heyuan, 517000, China.
| | - Tongzheng Liu
- State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou, 510632, China; The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.
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Elshanbary AA, Zaazouee MS, Nourelden AZ, Al-Kafarna M, Matar SG, Elsaeidy AS, Ragab KM, Elhady MM, Albadrani GM, Altyar AE, Kensara OA, Abdel-Daim MM. Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study. Eur J Cancer Prev 2024; 33:321-333. [PMID: 38190207 DOI: 10.1097/cej.0000000000000869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
BACKGROUND AND AIMS Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast. MATERIALS AND METHODS Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software. RESULTS A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV. CONCLUSION In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Ghadeer M Albadrani
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh
| | - Ahmed E Altyar
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University
- Pharmacy Program, Batterjee Medical College, Jeddah
| | - Osama A Kensara
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah
| | - Mohamed M Abdel-Daim
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
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Lee J, Kim J, Woo B, Pesola A, Tikkanen O. The longitudinal relationship between levels of leisure-time physical activity and positive and negative affect among older foreign-born adults with mild cognitive impairment. Psychogeriatrics 2024; 24:778-788. [PMID: 38627982 DOI: 10.1111/psyg.13114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 02/21/2024] [Accepted: 03/05/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND The purpose of this study was to investigate the longitudinal impact of different levels of leisure-time physical activity (LTPA) participation on positive and negative affect among older foreign-born adults with mild cognitive impairment (MCI). METHODS This study used 2012 to 2020 data from the Health and Retirement Study data (n = 1206) that was analyzed using repeated measured multivariate analysis of covariance. RESULTS The high-level participation LTPA group reported higher positive affect and lower negative affect than the mid and low-level participation groups. The mid-level LTPA group also reported higher positive and lower negative affect than the low-level LTPA group. CONCLUSIONS This study provides evidence that high levels of LTPA participation contribute to an increase in positive affect and a reduction of negative affect among older foreign-born adults with MCI. The findings of this study will help fill the gap in research on the longitudinal relationship between levels of LTPA participation and positive and negative affect among older foreign-born adults.
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Affiliation(s)
- Jungjoo Lee
- School of Health Professions, College of Nursing and Health Professions, University of Southern Mississippi, Hattiesburg, Mississippi, USA
| | - Junhyoung Kim
- Department of Health Behavior, School of Public Health, Texas A&M University, College Station, Texas, USA
| | - Bomi Woo
- Department of Health Behavior, School of Public Health, Texas A&M University, College Station, Texas, USA
| | - Arto Pesola
- Active Life Lab South-Eastern Finland University of Applied Sciences, Mikkeli, Finland
| | - Olli Tikkanen
- Fibion Inc. Jyväskylä, Finland and Physical Activity Researcher Podcast, Jyväskylä, Finland
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9
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Szablewski L. Insulin Resistance: The Increased Risk of Cancers. Curr Oncol 2024; 31:998-1027. [PMID: 38392069 PMCID: PMC10888119 DOI: 10.3390/curroncol31020075] [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: 11/24/2023] [Revised: 01/15/2024] [Accepted: 02/10/2024] [Indexed: 02/24/2024] Open
Abstract
Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction of insulin signaling to blood glucose levels. This state is observed when muscle cells, adipose tissue, and liver cells, improperly respond to a particular concentration of insulin. Insulin resistance and related increased plasma insulin levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states observed in obesity and type 2 diabetes mellitus. Observations of cancer patients confirm that hyperinsulinemia is a major factor influencing obesity, type 2 diabetes, and cancer. Obesity and diabetes have been reported as risks of the initiation, progression, and metastasis of several cancers. However, both of the aforementioned pathologies may independently and additionally increase the cancer risk. The state of metabolic disorders observed in cancer patients is associated with poor outcomes of cancer treatment. For example, patients suffering from metabolic disorders have higher cancer recurrence rates and their overall survival is reduced. In these associations between insulin resistance and cancer risk, an overview of the various pathogenic mechanisms that play a role in the development of cancer is discussed.
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Affiliation(s)
- Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego 5 Str., 02-004 Warsaw, Poland
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10
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Trembath HE, Yeh JJ, Lopez NE. Gastrointestinal Malignancy: Genetic Implications to Clinical Applications. Cancer Treat Res 2024; 192:305-418. [PMID: 39212927 DOI: 10.1007/978-3-031-61238-1_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Advances in molecular genetics have revolutionized our understanding of the pathogenesis, progression, and therapeutic options for treating gastrointestinal (GI) cancers. This chapter provides a comprehensive overview of the molecular landscape of GI cancers, focusing on key genetic alterations implicated in tumorigenesis across various anatomical sites including GIST, colon and rectum, and pancreas. Emphasis is placed on critical oncogenic pathways, such as mutations in tumor suppressor genes, oncogenes, chromosomal instability, microsatellite instability, and epigenetic modifications. The role of molecular biomarkers in predicting prognosis, guiding treatment decisions, and monitoring therapeutic response is discussed, highlighting the integration of genomic profiling into clinical practice. Finally, we address the evolving landscape of precision oncology in GI cancers, considering targeted therapies and immunotherapies.
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Affiliation(s)
- Hannah E Trembath
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA
| | - Jen Jen Yeh
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA
| | - Nicole E Lopez
- Division of Colon and Rectal Surgery, Department of Surgery, University of California San Diego, 4303 La Jolla Village Drive Suite 2110, San Diego, CA, 92122, USA.
- Division of Surgical Oncology, Department of Surgery, University of North Carolina, 170 Manning Drive, CB#7213, 1150 Physician's Office Building, Chapel Hill, NC, 27599-7213, USA.
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11
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Xiong F, Dai Q, Zhang S, Bent S, Tahir P, Van Blarigan EL, Kenfield SA, Chan JM, Schmajuk G, Graff RE. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev 2024; 40:e3709. [PMID: 37545374 DOI: 10.1002/dmrr.3709] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 05/05/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023]
Abstract
Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00-1.20), ER- (RR = 1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR = 1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.
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Affiliation(s)
- Fanxiu Xiong
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
| | - Qichen Dai
- Department of Breast Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sihan Zhang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Stephen Bent
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Psychiatry, University of California, San Francisco, San Francisco, California, USA
| | - Peggy Tahir
- UCSF Library, University of California, San Francisco, San Francisco, California, USA
| | - Erin L Van Blarigan
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Urology, University of California, San Francisco, San Francisco, California, USA
| | - Stacey A Kenfield
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Urology, University of California, San Francisco, San Francisco, California, USA
| | - June M Chan
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Urology, University of California, San Francisco, San Francisco, California, USA
| | - Gabriela Schmajuk
- Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Rebecca E Graff
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
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12
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Wu X, Peng L, Luo H, Xu Z, Wang J, Gu H, Wang Y, Xiao Y, Zhang C, Xiang L. Adherence to diabetes risk reduction diet and the risk of head and neck cancer: a prospective study of 101,755 American adults. Front Nutr 2023; 10:1218632. [PMID: 37810918 PMCID: PMC10556244 DOI: 10.3389/fnut.2023.1218632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 08/28/2023] [Indexed: 10/10/2023] Open
Abstract
Background Adherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association. Methods The present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC. Results During a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose-response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p < 0.001 for trend) compared to current or former smokers (p = 0.044 for interaction). The primary association of DDRD and HNC risk remained robust after several sensitivity analyses. Regarding the individual components of DRRD, an inverse association was also observed between the risk of HNC and increased intake of cereal fiber and whole fruit (all p < 0.05 for trend). Conclusion Our findings provide evidence that following the DRRD pattern may reduce the risk of NHC, especially for non-smokers.
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Affiliation(s)
- Xia Wu
- Department of Health Management Centre, Chongqing General Hospital, Chongqing, China
| | - Linglong Peng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haoyun Luo
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhiquan Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jijian Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haitao Gu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yaxu Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yi Xiao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chaohua Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ling Xiang
- Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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13
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Sankofi BM, Valencia-Rincón E, Sekhri M, Ponton-Almodovar AL, Bernard JJ, Wellberg EA. The impact of poor metabolic health on aggressive breast cancer: adipose tissue and tumor metabolism. Front Endocrinol (Lausanne) 2023; 14:1217875. [PMID: 37800138 PMCID: PMC10548218 DOI: 10.3389/fendo.2023.1217875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 08/30/2023] [Indexed: 10/07/2023] Open
Abstract
Obesity and type 2 diabetes are chronic metabolic diseases that impact tens to hundreds of millions of adults, especially in developed countries. Each condition is associated with an elevated risk of breast cancer and with a poor prognosis after treatment. The mechanisms connecting poor metabolic health to breast cancer are numerous and include hyperinsulinemia, inflammation, excess nutrient availability, and adipose tissue dysfunction. Here, we focus on adipose tissue, highlighting important roles for both adipocytes and fibroblasts in breast cancer progression. One potentially important mediator of adipose tissue effects on breast cancer is the fibroblast growth factor receptor (FGFR) signaling network. Among the many roles of FGFR signaling, we postulate that key mechanisms driving aggressive breast cancer include epithelial-to-mesenchymal transition and cellular metabolic reprogramming. We also pose existing questions that may help better understand breast cancer biology in people with obesity, type 2 diabetes, and poor metabolic health.
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Affiliation(s)
- Barbara Mensah Sankofi
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Estefania Valencia-Rincón
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Malika Sekhri
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Adriana L. Ponton-Almodovar
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
- Nicolas V. Perricone Division of Dermatology, Michigan State University, East Lansing, MI, United States
- Department of Medicine, Michigan State University, East Lansing, MI, United States
| | - Jamie J. Bernard
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
- Nicolas V. Perricone Division of Dermatology, Michigan State University, East Lansing, MI, United States
- Department of Medicine, Michigan State University, East Lansing, MI, United States
| | - Elizabeth A. Wellberg
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
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14
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Chaturvedi S, Biswas M, Sadhukhan S, Sonawane A. Role of EGFR and FASN in breast cancer progression. J Cell Commun Signal 2023:10.1007/s12079-023-00771-w. [PMID: 37490191 DOI: 10.1007/s12079-023-00771-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 05/22/2023] [Indexed: 07/26/2023] Open
Abstract
Breast cancer (BC) emerged as one of the life-threatening diseases among females. Despite notable improvements made in cancer detection and treatment worldwide, according to GLOBACAN 2020, BC is the fifth leading cancer, with an estimated 1 in 6 cancer deaths, in a majority of countries. However, the exact cause that leads to BC progression still needs to be determined. Here, we reviewed the role of two novel biomarkers responsible for 50-70% of BC progression. The first one is epidermal growth factor receptor (EGFR) which belongs to the ErbB tyrosine kinases family, signalling pathways associated with it play a significant role in regulating cell proliferation and division. Another one is fatty acid synthase (FASN), a key enzyme responsible for the de novo lipid synthesis required for cancer cell development. This review presents a rationale for the EGFR-mediated pathways, their interaction with FASN, communion of these two biomarkers with BC, and improvements to overcome drug resistance caused by them.
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Affiliation(s)
- Suchi Chaturvedi
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Khandwa Road, Simrol, Madhya Pradesh, 453552, India
| | - Mainak Biswas
- School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, Odisha, 751024, India
| | - Sushabhan Sadhukhan
- Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad, Kerala, 678623, India.
- Physical & Chemical Biology Laboratory and Department of Biological Sciences and Engineering, Indian Institute of Technology Palakkad, Palakkad, Kerala, 678623, India.
| | - Avinash Sonawane
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Khandwa Road, Simrol, Madhya Pradesh, 453552, India.
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15
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Sun X, Zhang Q, Kadier K, Hu P, Liu X, Liu J, Yan Y, Sun C, Yau V, Lowe S, Meng M, Liu Z, Zhou M. Association between diabetes status and breast cancer in US adults: findings from the US National Health and Nutrition Examination Survey. Front Endocrinol (Lausanne) 2023; 14:1059303. [PMID: 37415670 PMCID: PMC10321597 DOI: 10.3389/fendo.2023.1059303] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 05/16/2023] [Indexed: 07/08/2023] Open
Abstract
OBJECTIVES The aim of this study was to investigate the association between diabetes status and the risk of breast cancer among adult Americans, exploring the impact of BMI, age, and race on this relationship. METHODS A cross-sectional analysis of 8,249 individuals from the National Health and Nutrition Examination Survey (NHANES) was conducted. Diabetes was categorized as type 2 diabetes and prediabetes, with both conditions diagnosed according to the ADA 2014 guidelines. The association between diabetes status and breast cancer risk was explored using multiple logistic regression analysis. RESULTS Patients with diabetes had higher odds of breast cancer (OR: 1.51; 95% CI 1.00 to 2.28), Using the two-piecewise linear regression model, it was observed that there is a threshold effect in the risk of breast cancer occurrence at the age of 52 years. Specifically, the risk of breast cancer is relatively low before the age of 52 but increases significantly after this age. CONCLUSIONS This study identified a significant association between diabetes status and breast cancer risk among adult Americans. We also found a threshold effect in breast cancer occurrence at the age of 52. Age was significantly associated with breast cancer risk in both Non-Hispanic White and Non-Hispanic Black individuals. These findings underscore the importance of diabetes management, maintaining a healthy BMI, and age-related risk considerations in reducing breast cancer risk.
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Affiliation(s)
- Xingyu Sun
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
- Department of Gynecology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Qiangsong Zhang
- Emergency Department, East China Hospital affiliated to Fudan University, Shanghai, China
| | - Kaisaierjiang Kadier
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Pengcheng Hu
- Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaozhu Liu
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jialing Liu
- Department of Phase I Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yulu Yan
- Clinical Medical School, the Southwest Medical University, Luzhou, Sichuan, China
| | - Chenyu Sun
- Department of General Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Thyroid and Breast Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Vicky Yau
- Division of Oral and Maxillofacial Surgery, Columbia University Irving Medical Center, New York, NY, United States
| | - Scott Lowe
- College of Osteopathic Medicine, Kansas City University, Kansas City, MO, United States
| | - Muzi Meng
- UK Program Site, American University of the Caribbean School of Medicine, Preston, United Kingdom
- Bronxcare Health System, The Bronx, NY, United States
| | - Ziru Liu
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Meirong Zhou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
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16
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Sarkar MS, Mia MM, Amin MA, Hossain MS, Islam MZ. Bioinformatics and network biology approach to identifying type 2 diabetes genes and pathways that influence the progression of breast cancer. Heliyon 2023; 9:e16151. [PMID: 37234659 PMCID: PMC10205526 DOI: 10.1016/j.heliyon.2023.e16151] [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: 11/30/2022] [Revised: 04/28/2023] [Accepted: 05/07/2023] [Indexed: 05/28/2023] Open
Abstract
Breast cancer is the second most prevalent malignancy affecting women. Postmenopausal women breast tumor is one of the top causes of death in women, accounting for 23% of cancer cases. Type 2 diabetes, a worldwide pandemic, has been connected to a heightened risk of several malignancies, although its association with breast cancer is still uncertain. In comparison to non-diabetic women, women with T2DM had a 23% elevated likelihood of developing breast cancer. It is difficult to determine causative or genetic susceptibility that connect T2DM and breast cancer. We created a large-scale network-based quantitative approach employing unbiased methods to discover abnormally amplified genes in both T2DM and breast cancer, to solve these issues. We performed transcriptome analysis to uncover identical genetic biomarkers and pathways to clarify the connection between T2DM and breast cancer patients. In this study, two RNA-seq datasets (GSE103001 and GSE86468) from the Gene Expression Omnibus (GEO) are used to identify mutually differentially expressed genes (DEGs) for breast cancer and T2DM, as well as common pathways and prospective medicines. Firstly, 45 shared genes (30 upregulated and 15 downregulated) between T2D and breast cancer were detected. We employed gene ontology and pathway enrichment to characterize prevalent DEGs' molecular processes and signal transduction pathways and observed that T2DM has certain connections to the progression of breast cancer. Using several computational and statistical approaches, we created a protein-protein interactions (PPI) network and revealed hub genes. These hub genes can be potential biomarkers, which may also lead to new therapeutic strategies for investigated diseases. We conducted TF-gene interactions, gene-microRNA interactions, protein-drug interactions, and gene-disease associations to find potential connections between T2DM and breast cancer pathologies. We assume that the potential drugs that emerged from this study could be useful therapeutic values. Researchers, doctors, biotechnologists, and many others may benefit from this research.
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Affiliation(s)
- Md Sumon Sarkar
- Department of Pharmacy, Islamic University, Kushtia-7003, Bangladesh
| | - Md Misor Mia
- Department of Pharmacy, Islamic University, Kushtia-7003, Bangladesh
| | - Md Al Amin
- Department of Computer Science & Engineering, Prime University, Dhaka-1216, Bangladesh
| | - Md Sojib Hossain
- Department of Mathematics, Govt. Bangla College, Dhaka-1216, Bangladesh
| | - Md Zahidul Islam
- Department of Information & Communication Technology, Islamic University, Kushtia-7003, Bangladesh
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17
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Chan RNC, Chan RNF, Chou OHI, Tse G, Lee S. Lower risks of incident colorectal cancer in SGLT2i users compared to DPP4i users: A propensity score-matched study with competing risk analysis. Eur J Intern Med 2023; 110:125-127. [PMID: 36732129 DOI: 10.1016/j.ejim.2023.01.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 01/17/2023] [Accepted: 01/25/2023] [Indexed: 02/01/2023]
Affiliation(s)
| | | | - Oscar Hou In Chou
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China; Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China; Kent and Medway Medical School, University of Kent and Canterbury Christ Church, Canterbury, Kent, CT2 7NT, UK; Laboratory of Cardiovascular Physiology, CULKS Health Science Institute, Shatin, Hong Kong, China; School of Nursing and Health Studies, Hong Kong Metropolitan University, Homantin, Hong Kong, China.
| | - Sharen Lee
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China.
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18
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Graversen SB, Nannsen AØ, Bjerg L, Larsen MB, Andersen B, Laurberg T. The impact of diabetes on cancer detection during the prevalence round of a national screening program for colorectal cancer. Diabet Med 2023; 40:e15043. [PMID: 36655559 DOI: 10.1111/dme.15043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/21/2022] [Accepted: 01/10/2023] [Indexed: 01/20/2023]
Abstract
AIMS Diabetes is associated with a higher risk of colorectal cancer (CRC) and inferior survival after CRC. Screening may enable the early detection of CRC. We aimed to assess the impact of diabetes on cancer detection and disease stage during the prevalence round of a national CRC screening program. METHODS We performed a register-based cohort study based on the randomized procedure for inviting Danish residents aged 50-74 years to the prevalence round of national CRC screening program in 2014-2017. By comparing the random half of the population who had been invited by 1 May 2016 with the not yet invited half, the effect of screening was assessed by the detection of CRC and disease stage among individuals with and without diabetes. Further, the impact of diabetes on the screening participation rate was calculated. RESULTS By randomisation, 504,673 individuals had been invited to the CRC screening by 1 May 2016, and 549,359 individuals had not yet been invited. The diabetes prevalence was 10% in both groups. When comparing those not yet invited to those invited, the effect of screening on the number of detected cancers per 100,000 individuals was higher in those with diabetes (from 207 to 494 cancers) than in those without diabetes (from 147 to 364 cancers), and screening resulted in overall higher proportions of stage I cancer. Among those invited to screening, the participation rate was 9.1% lower (95% CI: 8.7%-9.5%) in individuals with versus without diabetes. CONCLUSIONS Despite a lower participation rate, the effect of CRC screening was higher in individuals with diabetes.
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Affiliation(s)
| | | | - Lasse Bjerg
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N, Denmark
- Department of Public Health, Aarhus University, Aarhus C, Denmark
| | - Mette Bach Larsen
- Department of Public Health Programmes, University Research Clinic for Cancer Screening, Randers Regional Hospital, Randers NØ, Denmark
| | - Berit Andersen
- Department of Public Health Programmes, University Research Clinic for Cancer Screening, Randers Regional Hospital, Randers NØ, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Tinne Laurberg
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N, Denmark
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19
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Ye X, Zhang Y, He Y, Sheng M, Huang J, Lou W. Association between Consumption of Artificial Sweeteners and Breast Cancer Risk: A Systematic Review and Meta-Analysis of Observational Studies. Nutr Cancer 2023; 75:795-804. [PMID: 36795026 DOI: 10.1080/01635581.2023.2178957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
Abstract
This study intends to conduct a meta-analysis based on existing research results to further investigate their relationship between artificial sweetener exposure and breast cancer risk. An electronic database literature search was performed up to July 2022, using PubMed, Web of Science, Ovid and Scopus. The relationship between artificial sweetener exposure and breast cancer (BC) incidence was evaluated by odds ratio (OR) and 95% confidence interval (CI). Among the five studies (two case-control studies and three cohort studies) that met the inclusion criteria, 314,056 participants were recruited in the cohort study, 4,043 cancer cases and 3,910 controls were recruited in the case-control study. It was found that exposure of artificial sweeteners was not related to the risk of BC (OR = 0.98, 95% CI = [0.94-1.03]). Subgroup analysis showed that compared with the non-exposure/very-low-dose group, the exposure to low, medium and high doses of artificial sweeteners were not associated with the risk of BC, which were OR = 1.01, 95% CI = [0.95-1.07], OR = 0.98, 95% CI = [0.93-1.02], OR = 0.88, 95% CI = [0.74-1.06], respectively. This study confirmed that there was no relationship between the exposure of artificial sweeteners and the incidence of BC.
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Affiliation(s)
- Xia Ye
- General Family Medicine, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China
| | - Yeyuan Zhang
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yujing He
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Mingyuan Sheng
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jianing Huang
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wenzhu Lou
- General Family Medicine, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China
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Prognostic Relevance of Type 2 Diabetes and Metformin Treatment in Head and Neck Melanoma: Results from a Population-Based Cohort Study. Curr Oncol 2022; 29:9660-9670. [PMID: 36547172 PMCID: PMC9777346 DOI: 10.3390/curroncol29120758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/24/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Type 2 Diabetes (DM2) and the consecutively daily use of antidiabetic medication are characterized by a frequent prevalence worldwide and were shown to impact the initiation and progression of malignant diseases. While these effects were observed in a variety of malignancies, comprehensive data about the role of DM2 and antidiabetic drugs in the outcome of head and neck melanoma (HNM) patients are missing. METHODS This retrospective population-based cohort study included 382 HNM patients from Eastern Bavaria having received tumor resection to negative margins between 2010 and 2017. Recurrence-free survival (RFS) was evaluated with regard to DM2 and routine metformin intake. Statistical analysis was performed by uni- and multivariate analyses. The median follow-up time was 5.6 years. RESULTS DM2 was diagnosed in 68 patients (17.8%), routine metformin intake was found in 39 cases (10.2%). The univariate survival analysis revealed impaired 5-year RFS in HNM patients with DM2 compared to non-diabetic controls (p = 0.016; 64.0% and 74.5%, respectively). The multivariate Cox regression substantiated this effect (HR = 1.980, 95% CI = 1.108-3.538, p = 0.021). In detail, the cumulative locoregional recurrence rate displayed the most far-reaching negative effect on the RFS of diabetic HNM patients (HR = 4.173, 95% CI = 1.628-10.697, p = 0.003). For metformin intake, a profound positive effect on the RFS in multivariate statistics was observed, both in the complete cohort (HR = 0.396, 95% CI = 0.177-0.884, p = 0.024) as well as in the cohort of diabetic HNM patients (HR = 0.352, 95% CI = 0.135-0.913, p = 0.032). CONCLUSIONS This study emphasizes that DM2 is a relevant comorbid condition in HNM patients, impairing patient survival. Metformin intake was associated with a favorable outcome in HNM patients, providing possible therapeutic implications for future adjuvant treatment regimes.
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Chan RNC, Lee TTL, Chou OHI, So J, Chung CT, Dee EC, Ng K, Tang P, Roever L, Liu T, Wong WT, Tse G, Lee S. Risk Factors of Pancreatic Cancer in Patients With Type 2 Diabetes Mellitus: The Hong Kong Diabetes Study. J Endocr Soc 2022; 6:bvac138. [PMID: 36267596 PMCID: PMC9562787 DOI: 10.1210/jendso/bvac138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Indexed: 11/19/2022] Open
Abstract
CONTEXT Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors. OBJECTIVE The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study. METHODS This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed. RESULTS This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01-1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30-2.81; P < .001), chronic kidney disease (HR: 1.81; 95% CI, 1.25-2.64; P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35-3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond. CONCLUSION Diabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs.
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Affiliation(s)
- Raymond Ngai Chiu Chan
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Teddy Tai Loy Lee
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Oscar Hou In Chou
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Jenny So
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Cheuk To Chung
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Edward Christopher Dee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Kenrick Ng
- Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Pias Tang
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
| | - Leonardo Roever
- Department of Clinical Research, Federal University of Uberlandia, Uberlandia, Brazil
| | - Tong Liu
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Wing Tak Wong
- School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Gary Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
- Kent and Medway Medical School, University of Kent and Canterbury Christ Church University, Canterbury, CT2 7NT, UK
| | - Sharen Lee
- Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China–UK Collaboration, Hong Kong, China
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22
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Yoo TK, Lee MY, Lee SA, Cheong ES, Seo MH, Sung KC. Association of Glycosylated Hemoglobin Level and Cancer-Related Mortality in Patients without Diabetes. J Clin Med 2022; 11:5933. [PMID: 36233800 PMCID: PMC9570990 DOI: 10.3390/jcm11195933] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/01/2022] [Accepted: 10/06/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Previous studies have reported that abnormal glucose metabolism is associated with poor cancer outcomes. Glycated hemoglobin A1c (HbA1c) is an important indicator of glucose metabolism. This study aimed to investigate the relationship between nondiabetic HbA1c levels and cancer-related mortality. METHODS This was a retrospective cohort study of Koreans who attended an annual or biennial health checkup program. The study group was categorized based on the quintile of HbA1c level (Q1, 3.0-5.1%; Q2, 5.2-5.3%; Q3, 5.4%; Q4, 5.5-5.6%, Q5, 5.7-6.4%). Cancer-related mortality was determined using the mortality data from the Korea National Statistical Office. Participants with an established diagnosis of diabetes or cancer were excluded. Cancer-related mortality was assessed depending on each HbA1c level with adjustment for factors that could influence mortality. RESULTS A total of 589,457 participants were included in this study. During a median follow-up duration of 6.99 years, 1712 cancer-related deaths were reported. The risk of cancer-related mortality was significantly higher in the Q5 group (hazard ratio (HR) 1.23, range 1.02-1.47 in model 1; HR 1.25, range 1.04-1.50 in model 2). HbA1c levels were linearly associated with cancer-related deaths (Ptrend = 0.021 in model 1; 0.013 in model 2). HbA1c level and colorectal, stomach, and lung cancer mortality exhibited a positive relationship, whereas liver cancer-related mortality showed an inverse relationship with HbA1c level (Ptrend = 0.001). CONCLUSIONS Our study showed that abnormal glucose metabolism is significantly associated with cancer-related mortality, and its relationship varies with each type of cancer.
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Affiliation(s)
- Tae Kyung Yoo
- Department of Medicine, MetroWest Medical Center, Framingham, MA 01702, USA
| | - Mi Yeon Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea
| | - Sul A. Lee
- Nephrology Division, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Eun Sun Cheong
- Division of Cardiology, Department of Internal Medicine, Seoul Eulji Hospital, Eulji University School of Medicine, Seoul 01830, Korea
| | - Mi Hae Seo
- Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi 39371, Korea
| | - Ki Chul Sung
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea
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23
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Abstract
The traditional complications of diabetes mellitus are well known and continue to pose a considerable burden on millions of people living with diabetes mellitus. However, advances in the management of diabetes mellitus and, consequently, longer life expectancies, have resulted in the emergence of evidence of the existence of a different set of lesser-acknowledged diabetes mellitus complications. With declining mortality from vascular disease, which once accounted for more than 50% of deaths amongst people with diabetes mellitus, cancer and dementia now comprise the leading causes of death in people with diabetes mellitus in some countries or regions. Additionally, studies have demonstrated notable links between diabetes mellitus and a broad range of comorbidities, including cognitive decline, functional disability, affective disorders, obstructive sleep apnoea and liver disease, and have refined our understanding of the association between diabetes mellitus and infection. However, no published review currently synthesizes this evidence to provide an in-depth discussion of the burden and risks of these emerging complications. This Review summarizes information from systematic reviews and major cohort studies regarding emerging complications of type 1 and type 2 diabetes mellitus to identify and quantify associations, highlight gaps and discrepancies in the evidence, and consider implications for the future management of diabetes mellitus.
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Affiliation(s)
- Dunya Tomic
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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24
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Laurberg T, Frandsen S, Larsen HM, Lehrskov LL, Graversen SB, Drewes AM, Emmertsen KJ, Krogh K. The impact of type 2 diabetes on long-term gastrointestinal sequelae after colorectal cancer surgery: national population-based study. BJS Open 2022; 6:6673944. [PMID: 35998089 PMCID: PMC9397505 DOI: 10.1093/bjsopen/zrac095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 06/16/2022] [Accepted: 06/26/2022] [Indexed: 12/24/2022] Open
Abstract
Background Long-term gastrointestinal sequelae are common after colorectal cancer surgery, but the impact of type 2 diabetes (T2D) is unknown. Methods In a cross-sectional design, questionnaires regarding bowel function and quality of life (QoL) were sent to all Danish colorectal cancer survivors, who had undergone surgery between 2001 and 2014 and had more than 2 years follow-up without relapse. The prevalence of long-term gastrointestinal sequelae among colorectal cancer survivors with and without T2D were compared while stratifying for type of surgical resection and adjusting for age, sex, and time since surgery. Results A total of 8747 out of 14 488 colorectal cancer survivors answered the questionnaire (response rate 60 per cent), consisting of 3116 right-sided colonic, 2861 sigmoid, and 2770 rectal resections. Of these, 690 (7.9 per cent) had a diagnosis of T2D before surgery. Survivors with T2D following rectal resection had a 15 per cent (95 per cent c.i. 7.8 to 22) higher absolute risk of major low anterior resection syndrome, whereas survivors with T2D following right-sided and sigmoid resection had an 8 per cent higher risk of constipation (P < 0.001) but otherwise nearly the same long-term risk of bowel symptoms as those without T2D. For all types of colorectal cancer resections, T2D was associated with a 6–10 per cent higher risk of severe pain (P < 0.035) and a 4–8 per cent higher risk of impaired QoL. Conclusion T2D at time of surgery was associated with a higher risk of long-term bowel dysfunction after rectal resection, but not after colon resection excluding a higher risk of constipation. T2D was associated with a slightly higher frequency of severe pain and inferior QoL after both rectal and colonic cancer resection.
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Affiliation(s)
- Tinne Laurberg
- Steno Diabetes Center Aarhus, Aarhus University Hospital , Aarhus , Denmark
| | | | - Helene M Larsen
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects after Cancer in the Pelvic Organs , Aarhus/Aalborg , Denmark
- Department of Emergency, Regional Hospital Horsens , Horsens , Denmark
| | - Louise L Lehrskov
- The Centre for Physical Activity Research, Copenhagen University Hospital – Rigshospitalet , Copenhagen , Denmark
| | | | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital , Aalborg , Denmark
| | - Katrine J Emmertsen
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects after Cancer in the Pelvic Organs , Aarhus/Aalborg , Denmark
- Department of Surgery, Regional Hospital Randers , Randers , Denmark
| | - Klaus Krogh
- Steno Diabetes Center Aarhus, Aarhus University Hospital , Aarhus , Denmark
- Department of Hepatology and Gastroenterology, Aarhus University Hospital , Aarhus , Denmark
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25
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Campbell PT, Newton CC, Jacobs EJ, McCullough ML, Wang Y, Rees-Punia E, Guinter MA, Murphy N, Koshiol J, Dehal AN, Rohan T, Strickler H, Petrick J, Gunter M, Zhang X, McGlynn KA, Pollak M, Patel AV, Gapstur SM. Prospective associations of hemoglobin A 1c and c-peptide with risk of diabetes-related cancers in the Cancer Prevention Study-II Nutrition Cohort. CANCER RESEARCH COMMUNICATIONS 2022; 2:653-662. [PMID: 36712480 PMCID: PMC9881454 DOI: 10.1158/2767-9764.crc-22-0082] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/05/2022] [Accepted: 06/21/2022] [Indexed: 02/02/2023]
Abstract
Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A1c (HbA1c) and c-peptide with cancers associated with self-reported T2DM. This study was drawn from a prospective cohort of 32,383 women and men who provided blood specimens at baseline: c-peptide and HbA1c were assessed in 3,000 randomly selected participants who were cancer-free-at-baseline and an additional 2,281 participants who were cancer-free-at-baseline and subsequently diagnosed with incident colorectal, liver, pancreatic, female breast, endometrial, ovarian, bladder, or kidney cancers. Weighted-Cox regression models estimated hazards ratios (HRs) and 95% confidence intervals (CI), adjusted for covariates. C-peptide was associated with higher risk of liver cancer (per standard deviation (SD) HR: 1.80; 95%CI: 1.32-2.46). HbA1c was associated with higher risk of pancreatic cancer (per SD HR: 1.21 95%CI 1.05-1.40) and with some suggestion of higher risks for all-cancers-of-interest (per SD HR: 1.05; 95%CI: 0.99-1.11) and colorectal (per SD HR: 1.09; 95%CI: 0.98-1.20), ovarian (per SD HR: 1.18; 95%CI 0.96-1.45) and bladder (per SD HR: 1.08; 95%CI 0.96-1.21) cancers. Compared to no self-reported T2DM and HbA1c <6.5% (reference group), self-reported T2DM and HbA1c <6.5% (i.e., T2DM in good glycemic control) was not associated with risk of colorectal cancer, whereas it was associated with higher risks of all-cancers-of-interest combined (HR: 1.28; 95%CI: 1.01-1.62), especially for breast and endometrial cancers. Additional large, prospective studies are needed to further explore the roles of hyperglycemia, hyperinsulinemia, and related metabolic traits with T2DM-associated cancers to better understand the mechanisms underlying the self-reported T2DM-cancer association and to identify persons at higher cancer risk.
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Affiliation(s)
- Peter T. Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | - Christina C. Newton
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | - Eric J. Jacobs
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | | | - Ying Wang
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | - Erika Rees-Punia
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | - Mark A. Guinter
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France
| | - Jill Koshiol
- Division of Cancer Epidemiology and Genetics, NIH, NCI, Rockville, Maryland
| | - Ahmed N. Dehal
- Department of Clinical Science, Kaiser Permanente Bernard J Tyson School of Medicine, Panorama City, California
| | - Thomas Rohan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
| | - Howard Strickler
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
| | - Jessica Petrick
- Slone Epidemiology Center at Boston University, Boston, Massachusetts
| | - Marc Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | | | - Michael Pollak
- Depsartment of Medicine and Oncology, McGill University, Montreal, Quebec, Canada
| | - Alpa V. Patel
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
| | - Susan M. Gapstur
- Population Science Department, American Cancer Society (ACS), Atlanta, Georgia
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26
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Kim J, Lee J, Kim YS, Park SH. Identifying the Relationship between Leisure Walking and Prevalence of Alzheimer’s Disease and Other Dementias. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19138076. [PMID: 35805735 PMCID: PMC9265613 DOI: 10.3390/ijerph19138076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/20/2022] [Accepted: 06/27/2022] [Indexed: 11/30/2022]
Abstract
The literature suggests that leisure walking can play an important role in preventing dementia. The purpose of the present study was to investigate the relationship between leisure walking and the prevalence of Alzheimer’s disease (AD) and other dementias among older adults. Using the 2020 Health and Retirement Study (HRS), 4581 responses constituted the sample for the present study. A hierarchical logit regression analysis was conducted to investigate the relationship between leisure walking and the prevalence of AD and dementia. The results show that leisure walking has been negatively associated with the prevalence of AD and other dementias—that is, they indicate that older adults who frequently engaged in leisure walking were less likely to develop AD and other dementias. This finding suggests the importance of leisure walking as a dementia prevention program for older adults.
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Affiliation(s)
- Junhyoung Kim
- Department of Health & Wellness Design, Indiana University, Bloomington, IN 47405, USA; (J.K.); (J.L.)
| | - Jungjoo Lee
- Department of Health & Wellness Design, Indiana University, Bloomington, IN 47405, USA; (J.K.); (J.L.)
| | - Yu-Sik Kim
- Department of Sports Sciences, Seoul National University of Science and Technology, Seoul 01811, Korea;
| | - Se-Hyuk Park
- Department of Sports Sciences, Seoul National University of Science and Technology, Seoul 01811, Korea;
- Correspondence:
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Li D, Shao J, Cao B, Zhao R, Li H, Gao W, Chen P, Jin L, Cao L, Ji S, Dong G. The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside. Front Oncol 2022; 12:848594. [PMID: 35747797 PMCID: PMC9209713 DOI: 10.3389/fonc.2022.848594] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 05/09/2022] [Indexed: 12/30/2022] Open
Abstract
Neutrophil extracellular traps (NETs), products of neutrophil death when exposed to certain stimuli, were first proposed as a type of response to bacterial infection in infectious diseases. Since then, extensive studies have discovered its involvement in other non-infectious inflammatory diseases including thromboembolism, autoimmune diseases, and cancer. Colorectal cancer (CRC) is one of the most common malignancies in the world. NET formation is closely associated with tumorigenesis, progression, and metastasis in CRC. Therefore, the application of NETs in clinical practice as diagnostic biomarkers, therapeutic targets, and prognostic predictors has a promising prospect. In addition, therapeutics targeting NETs are significantly efficient in halting tumor progression in preclinical cancer models, which further indicates its potential clinical utility in cancer treatment. This review focuses on the stimuli of NETosis, its pro-tumorigenic activity, and prospective clinical utility primarily in but not limited to CRC.
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Affiliation(s)
- Dingchang Li
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | | | - Bo Cao
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Ruiyang Zhao
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Hanghang Li
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Wenxing Gao
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Peng Chen
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Lujia Jin
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Medical School of Chinese PLA, Beijing, China
| | - Li Cao
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Shuaifei Ji
- Medical School of Chinese PLA, Beijing, China
- *Correspondence: Shuaifei Ji, ; Guanglong Dong,
| | - Guanglong Dong
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- *Correspondence: Shuaifei Ji, ; Guanglong Dong,
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Tang S, Wen P, Li K, Deng J, Yang B. Tumor targetable and pH-sensitive polymer nanoparticles for simultaneously improve the Type 2 Diabetes Mellitus and malignant breast cancer. Bioengineered 2022; 13:9754-9765. [PMID: 35411835 PMCID: PMC9162024 DOI: 10.1080/21655979.2022.2060721] [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] [Indexed: 11/02/2022] Open
Abstract
In the recent study, we have developed novel tumor targetable and pH-sensitive PLGA nanoparticles co-loaded with camptothecin (CPT) and metformin (Metf) to simultaneously improve the Type 2 Diabetes Mellitus (T2DM) and malignant breast cancer. To improve the drug loading efficiency, the hydrophobic CPT was conjugated with PLGA polymer by the pH-sensitive hydrazone bonds (hyd). Then, the Metf was physically loaded into the hydrophobicity inner core of CPT-conjugated PLGA nanocomplex to form the dual drugs-loaded nanoparticles (NP/CPT-Metf). Furthermore, on the surface of NP/CPT-Metf was modified with tumor-homing CGKRK peptides to obtain the tumor targetable and pH-sensitive polymer nanoparticles (CNP/CPT-Metf). It was demonstrated that the developed CNP/CPT-Metf displayed sufficient sensitivity to the weak acidic tumor microenvironment. Besides, excellent ability of CNP/CPT-Metf to mediate accumulation of drugs in cells and tumor tissues finally in turn resulted in a signal enhanced anti-tumor effect. Furthermore, it was demonstrated as well that CNP/CPT-Metf was able of significantly alleviating the type 2 diabetes mellitus in diabetic mice. In summary, the developed multifunctional polymer nanoparticles might represent a promising strategy for simultaneously improve the T2DM and treat malignant breast cancer.
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Affiliation(s)
- Shi Tang
- Department of Breast Surgery, Dongguan City Maternal & Children Health Hospital, Dongguan, Guangdong, China
| | - Peiqi Wen
- Department of Breast Surgery, Dongguan City Maternal & Children Health Hospital, Dongguan, Guangdong, China
| | - Kaiheng Li
- Department of Breast Surgery, Dongguan City Maternal & Children Health Hospital, Dongguan, Guangdong, China
| | - Jiehua Deng
- Department of Breast Surgery, Dongguan City Maternal & Children Health Hospital, Dongguan, Guangdong, China
| | - Bo Yang
- Department of Breast Surgery, Dongguan City Maternal & Children Health Hospital, Dongguan, Guangdong, China
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Risk Factors of Young-Onset Colorectal Cancer: Analysis of a Large Population-Based Registry. Can J Gastroenterol Hepatol 2022; 2022:3582443. [PMID: 35223684 PMCID: PMC8866030 DOI: 10.1155/2022/3582443] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 01/19/2022] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND As the third most common type of cancer in the United States, colorectal cancer (CRC) was previously thought to be rare in young populations. Despite a decrease in the overall incidence of CRC, the rate of new cases under 50 years old has been continuously increasing. AIM The purpose of our study was to analyze risk factors of young-onset CRC. METHODS Commercially available software platform, Explorys, was used to extract data from a collective healthcare database electronically. RESULTS In this database, 13,800 young adults (age 20-50) were diagnosed with primary colorectal malignancy. Compared to subjects with a previous family history of CRC who had an odds ratio of 17.78, those diagnosed with primary malignant neoplasm of breast and inflammatory bowel disease (ulcerative colitis and Crohn's) had odds ratios of 16.94, 4.4, and 3.7 for young-onset CRC, respectively. Patients with a history of alcohol abuse, smoking, obesity, diabetes mellitus, and hyperlipidemia had higher chances of developing young-onset CRC. In addition, the odds of CRC were lower in Hispanic ethnicity in comparison to Caucasians (OR: 0.54), with no statically significant differences between Caucasian, African American, and Asian populations. CONCLUSION Currently, this is an expansive study investigating the risk factors for early-onset CRC. The analysis showed factors such as family and individual history of IBD to have high association with early onset. Notably, an individual history of breast malignancy was strongly associated with early-onset CRC.
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He XC, Chen HY, Qiu Y, Tian L, Bao BS, Hao XP, Chen YH. Associations of iron status with breast cancer risk factors in adult women: Findings from National Health and Nutrition Examination Survey 2017-2018. J Trace Elem Med Biol 2021; 68:126867. [PMID: 34592676 DOI: 10.1016/j.jtemb.2021.126867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 08/24/2021] [Accepted: 09/22/2021] [Indexed: 11/25/2022]
Abstract
OBJECTIVE This study examined the association between iron status and a set of breast cancer risk factors among U.S. adult women aged 20-80 years. METHODS Data from National Health and Nutrition Examination Survey (2017-2018) were used to examine the relation between serum ferritin, serum iron and transferrin saturation with a set of breast cancer risk factors [body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin and HOMA-IR]. The multivariable linear regressions were used controlling for age, race/ethnicity, menopause status, education level, smoking status, alcohol consumption, physical activity, high-sensitivity C-reactive protein (hsCRP) and total energy intake. RESULTS HbA1c, BMI and waist circumference data were available for 1902 women with a fasting sample (n = 913) for fasting plasma glucose, insulin and HOMA-IR. Transferrin saturation had significant, inverse associations with BMI, waist circumference and HbA1c. The size of difference observed were that participants in the fourth quartile of transferrin saturation had a 4.50 kg/m2 smaller BMI, a 9.36 cm smaller waist circumference and a 0.1 % lower HbA1c level than participants in the first quartile. Similarly, serum iron concentrations were inversely associated with BMI and waist circumference. In addition, serum iron had significant, inverse associations with insulin and HOMA-IR. Sensitivity analyses among men gave similar results. For serum ferritin, there was a trend towards a positive association between waist circumference, HbA1c and fasting plasma glucose with serum ferritin. However, the associations did not reach statistical significance among women. CONCLUSIONS Iron status may impact breast cancer risk via effects on adiposity or glucose metabolism. The findings should be confirmed with further prospective data.
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Affiliation(s)
- Xiao-Chong He
- Department of Nursing Administration, Army Medical University, Chongqing, 400038, China.
| | - Hong-Ye Chen
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.
| | - Yue Qiu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.
| | - Lin Tian
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.
| | - Bao-Shi Bao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.
| | - Xiao-Peng Hao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.
| | - Yu-Hui Chen
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, 100039, China.
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Scalzo RL, Foright RM, Hull SE, Knaub LA, Johnson-Murguia S, Kinanee F, Kaplan J, Houck JA, Johnson G, Sharp RR, Gillen AE, Jones KL, Zhang AMY, Johnson JD, MacLean PS, Reusch JEB, Wright-Hobart S, Wellberg EA. Breast Cancer Endocrine Therapy Promotes Weight Gain With Distinct Adipose Tissue Effects in Lean and Obese Female Mice. Endocrinology 2021; 162:bqab174. [PMID: 34410380 PMCID: PMC8455348 DOI: 10.1210/endocr/bqab174] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Indexed: 12/19/2022]
Abstract
Breast cancer survivors treated with tamoxifen and aromatase inhibitors report weight gain and have an elevated risk of type 2 diabetes, especially if they have obesity. These patient experiences are inconsistent with, preclinical studies using high doses of tamoxifen which reported acute weight loss. We investigated the impact of breast cancer endocrine therapies in a preclinical model of obesity and in a small group of breast adipose tissue samples from women taking tamoxifen to understand the clinical findings. Mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in mesenchymal stem cells from adipose tissue, endocrine therapy was associated with adipose accumulation and more preadipocytes compared with estrogen-treated control mice but resulted in fewer adipocyte progenitors only in the context of HFHS. Analysis of subcutaneous adipose stromal cells revealed diet- and treatment-dependent effects of endocrine therapies on various cell types and genes, illustrating the complexity of adipose tissue estrogen receptor signaling. Breast cancer therapies supported adipocyte hypertrophy and associated with hepatic steatosis, hyperinsulinemia, and glucose intolerance, particularly in obese females. Current tamoxifen use associated with larger breast adipocyte diameter only in women with obesity. Our translational studies suggest that endocrine therapies may disrupt adipocyte progenitors and support adipocyte hypertrophy, potentially leading to ectopic lipid deposition that may be linked to a greater type 2 diabetes risk. Monitoring glucose tolerance and potential interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.
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Affiliation(s)
- Rebecca L Scalzo
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Center for Women’s Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA
| | - Rebecca M Foright
- Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Sara E Hull
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Leslie A Knaub
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Stevi Johnson-Murguia
- Department of Pathology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA
| | - Fotobari Kinanee
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Jeffrey Kaplan
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Julie A Houck
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Ginger Johnson
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Rachel R Sharp
- Department of Cell Biology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA
| | - Austin E Gillen
- Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Kenneth L Jones
- Department of Cell Biology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA
| | - Anni M Y Zhang
- Diabetes Research Group, Life Sciences Institute, Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - James D Johnson
- Diabetes Research Group, Life Sciences Institute, Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Paul S MacLean
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Center for Women’s Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Jane E B Reusch
- Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Center for Women’s Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA
| | - Sabrina Wright-Hobart
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Elizabeth A Wellberg
- Center for Women’s Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Department of Pathology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA
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Huybrechts I, Kliemann N, Perol O, Cattey-Javouhey A, Benech N, Maire A, Lignini T, Carretier J, Saurin JC, Fervers B, Gunter MJ. Feasibility Study to Assess the Impact of a Lifestyle Intervention during Colorectal Cancer Screening in France. Nutrients 2021; 13:3685. [PMID: 34835941 PMCID: PMC8621980 DOI: 10.3390/nu13113685] [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] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/15/2021] [Accepted: 10/16/2021] [Indexed: 11/21/2022] Open
Abstract
Current evidence suggests that 30-50% of cancers are attributable to established lifestyle risk factors. Cancer-screening has been identified as an opportunity for delivering advice on lifestyle behaviour change for cancer prevention. This study aimed to evaluate the feasibility and acceptance of promoting advice on the latest evidence-based lifestyle recommendations for cancer prevention at the time of colorectal cancer screening at two hospitals in Lyon, France. This feasibility study included 49 patients (20 men and 29 women) who were invited for colonoscopy. Patients received a leaflet with lifestyle recommendations for cancer prevention, accompanied with a logbook to plan and monitor their behavioural changes. Feedback from patients, hospital staff, and researchers was received via evaluation questionnaires (n = 26) completed after testing the educational material for at least two weeks and via two focus group discussions (n = 7 and n = 9 respectively) organized at the end of the study. All interviewed patients were interested in lowering their cancer risk, and the majority felt ready to change their lifestyle (88%), although most did not know how to decrease their risk of cancer (61%). All patients found the educational material easy to understand and sufficiently attractive and 50% of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks following the intervention. All hospital staff and almost all patients (92%) involved found that the screening program and the visits planned for colonoscopy was an appropriate moment to provide them with the educational material. This feasibility study has shown that the content, paper-based format, and time of delivery of the intervention were adequate. Health professionals seem to be willing to provide lifestyle recommendations, and patients appear interested in receiving advice for lowering their cancer risk during screening visits.
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Affiliation(s)
- Inge Huybrechts
- International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France; (N.K.); (T.L.); (M.J.G.)
| | - Nathalie Kliemann
- International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France; (N.K.); (T.L.); (M.J.G.)
| | - Olivia Perol
- Centre Léon Bérard, 69008 Lyon, France; (O.P.); (A.C.-J.); (A.M.); (J.C.); (B.F.)
| | - Anne Cattey-Javouhey
- Centre Léon Bérard, 69008 Lyon, France; (O.P.); (A.C.-J.); (A.M.); (J.C.); (B.F.)
| | - Nicolas Benech
- Service d’Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69003 Lyon, France; (N.B.); (J.-C.S.)
| | - Aurelia Maire
- Centre Léon Bérard, 69008 Lyon, France; (O.P.); (A.C.-J.); (A.M.); (J.C.); (B.F.)
| | - Tracy Lignini
- International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France; (N.K.); (T.L.); (M.J.G.)
| | - Julien Carretier
- Centre Léon Bérard, 69008 Lyon, France; (O.P.); (A.C.-J.); (A.M.); (J.C.); (B.F.)
| | - Jean-Christophe Saurin
- Service d’Hépato-Gastroentérologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69003 Lyon, France; (N.B.); (J.-C.S.)
| | - Beatrice Fervers
- Centre Léon Bérard, 69008 Lyon, France; (O.P.); (A.C.-J.); (A.M.); (J.C.); (B.F.)
| | - Marc J. Gunter
- International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France; (N.K.); (T.L.); (M.J.G.)
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Christensen RAG, Kirkham AA. Time-Restricted Eating: A Novel and Simple Dietary Intervention for Primary and Secondary Prevention of Breast Cancer and Cardiovascular Disease. Nutrients 2021; 13:3476. [PMID: 34684476 PMCID: PMC8537890 DOI: 10.3390/nu13103476] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 09/28/2021] [Accepted: 09/28/2021] [Indexed: 12/20/2022] Open
Abstract
There is substantial overlap in risk factors for the pathogenesis and progression of breast cancer (BC) and cardiovascular disease (CVD), including obesity, metabolic disturbances, and chronic inflammation. These unifying features remain prevalent after a BC diagnosis and are exacerbated by BC treatment, resulting in elevated CVD risk among survivors. Thus, therapies that target these risk factors or mechanisms are likely to be effective for the prevention or progression of both conditions. In this narrative review, we propose time-restricted eating (TRE) as a simple lifestyle therapy to address many upstream causative factors associated with both BC and CVD. TRE is simple dietary strategy that typically involves the consumption of ad libitum energy intake within 8 h, followed by a 16-h fast. We describe the feasibility and safety of TRE and the available evidence for the impact of TRE on metabolic, cardiovascular, and cancer-specific health benefits. We also highlight potential solutions for overcoming barriers to adoption and adherence and areas requiring future research. In composite, we make the case for the use of TRE as a novel, safe, and feasible intervention for primary and secondary BC prevention, as well as tertiary prevention as it relates to CVD in BC survivors.
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Affiliation(s)
| | - Amy A. Kirkham
- Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON M5S 2C9, Canada
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Incident Type 2 Diabetes Risk of Selective Estrogen Receptor Modulators in Female Patients with Breast Cancer. Pharmaceuticals (Basel) 2021; 14:ph14090925. [PMID: 34577625 PMCID: PMC8472249 DOI: 10.3390/ph14090925] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/10/2021] [Accepted: 09/13/2021] [Indexed: 12/12/2022] Open
Abstract
Accumulating evidence indicates a link between diabetes and cancer. Selective estrogen receptor modulators (SERMs) may increase diabetes risk via antiestrogen effects. This study investigated incident diabetes risk of SERM treatment and its effects on metastatic cancer and death prevention in breast cancer survivors. This retrospective cohort study included female patients with early-stage breast cancer, treated with or without SERMs, between 2008 and 2020 in a tertiary care hospital in Korea. Four propensity score-matched comparison pairs were designed: SERM use versus non-use, long-term use (≥1500 days) versus non-use, tamoxifen use versus non-use, and toremifene use versus non-use; then, logistic regression analysis was performed for risk analysis. SERMs in general were not associated with an elevated risk of diabetes; however, when used for ≥1500 days, SERMs—especially toremifene—substantially increased diabetes risk in breast cancer patients (OR 1.63, p = 0.048). Meanwhile, long-term SERM treatment was effective at preventing metastatic cancer (OR 0.20, p < 0.001) and death (OR 0.13, p < 0.001). SERM treatment, albeit generally safe and effective, may increase diabetes risk with its long-term use in women with breast cancer. Further studies are required to verify the association between toremifene treatment and incident diabetes.
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Abstract
Recently, several studies have demonstrated that heart failure (HF) may increase the risk of incident cancer. However, this association has not been statistically and systematically verified by any comprehensive pooled analyses. We performed a meta-analysis on cancer morbidity and co-mortality of adults with HF in a large sample size to explore the relationship between HF and the risk of developing cancer. From inception to April 2019, we searched PubMed and EMBASE for published relevant articles on patients with HF diagnosed with cancer afterwards, with reported outcomes of morbidity and mortality. Two investigators independently reviewed these included studies. Study data were independently extracted using predefined data extraction forms. Random and fixed-effects models were fit for the study duration. This analysis consisted of 4 cohort studies comprising 5,004,251 participants. The relative risk (RR) for incident cancer was 1.22 (95% confidence interval (CI), 1.13-1.33) indicating that patients with HF may have a higher risk of developing cancer. The pooled RR of co-mortality was 2.03 (95% CI, 1.13-3.65), indicating that HF associated with cancer increases the risk of mortality. In this meta-analysis and systematic review, our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality.
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Cheng HC, Chang TK, Su WC, Tsai HL, Wang JY. Narrative review of the influence of diabetes mellitus and hyperglycemia on colorectal cancer risk and oncological outcomes. Transl Oncol 2021; 14:101089. [PMID: 33838541 PMCID: PMC8058559 DOI: 10.1016/j.tranon.2021.101089] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/24/2021] [Accepted: 03/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) and hyperglycemia have been shown to have significant effects on the incidence, chemoresistance, and prognosis of colorectal cancer (CRC), as well as the outcomes of localized and metastatic CRC. Inflammation and endocrine effects may act as central mechanisms of DM and cancer and stimulate the insulin-like growth factor 1-phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (IGF-1-PI3K-AKT-mTOR) pathway. Dysregulation of the AMP-activated protein kinase (AMPK) pathway leads to metabolic imbalance and indicates cancer risk. The use of metformin for chemoprevention has been shown to reduce CRC and adenoma incidence through the upregulation of AMPK, which causes cell cycle arrest in the Gap 1-S (G1-S) phase and inhibits the mTOR pathway, even potentially reversing the epithelial-mesenchymal transition. However, evidence of the effects of metformin remain controversial in cancer prognosis. Several genes, such as transcription factor 7-like 2(TCF7L2), tumor protein P53 inducible nuclear protein 1(TP53INP1), gremlin 1 (GREM1), and potassium voltage-gated channel subfamily Q member 1(KCNQ1), are pleiotropically related to DM as well as cancer risk and prognosis. Epigenetic modification of members of the Let-7 family such as miR-497, miR-486, and miR-223 is strongly associated with impaired glucose tolerance and CRC risk. Herein we review the pathophysiological and epidemiological evidence as well as potential underlying molecular mechanisms by which DM and hyperglycemia affect CRC risk. We also suggest potential roles of glucose modulation in CRC therapy and propose an agenda for future research and clinical practice.
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Affiliation(s)
- Hsiu-Chung Cheng
- School of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan
| | - Tsung-Kun Chang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung City 807, Kaohsiung, Taiwan
| | - Wei-Chih Su
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung City 807, Kaohsiung, Taiwan
| | - Hsiang-Lin Tsai
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung City 807, Kaohsiung, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung City 807, Kaohsiung, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Liquid Biopsy and Cohort Research, Taiwan.
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Hui T, Shang C, Yang L, Wang M, Li R, Song Z. Metformin improves the outcomes in Chinese invasive breast cancer patients with type 2 diabetes mellitus. Sci Rep 2021; 11:10034. [PMID: 33976288 PMCID: PMC8113316 DOI: 10.1038/s41598-021-89475-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 04/27/2021] [Indexed: 02/01/2023] Open
Abstract
Early reports indicate that metformin, a clinical drug administered to treat type 2 diabetes mellitus (T2DM), was found to be associated with a better prognosis of cancer. The objective of this study was retrospectively analyzed the effect of metformin on the outcomes of Chinese breast cancer patients with T2DM. A total of 3757 primary invasive breast cancer patients who underwent surgery from January 2010 to December 2013 were enrolled. According to the medication treatment, all the patients were divided as non-diabetes group, metformin group and insulin group. The follow-up data for disease-free survival (DFS) and overall survival (OS) were obtained from 3553 patients (median follow up of 85 months) and estimated with the Kaplan–Meier method followed by a log-rank test. Multivariate Cox proportional hazards regression model was applied. The results showed that there was a significant survival difference among non-diabetes group, metformin group and insulin group, 5-year DFS was 85.8%, 96.1%, 73.0%, and 5-year OS was 87.3%, 97.1%, 73.3% respectively (P < 0.05). Prognostic analysis showed metformin was significantly associated with better DFS and OS. Our results suggested that metformin may have a good effect on the survival of invasive breast cancer patients with T2DM.
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Affiliation(s)
- Tianli Hui
- Breast Center, Hebei Medical University Fourth Affiliated Hospital, No. 169 Tianshan Street, Shijiazhuang, 050035, China
| | - Chao Shang
- Breast Center, Hebei Medical University Fourth Affiliated Hospital, No. 169 Tianshan Street, Shijiazhuang, 050035, China
| | - Liu Yang
- Breast Center, Hebei Medical University Fourth Affiliated Hospital, No. 169 Tianshan Street, Shijiazhuang, 050035, China
| | - Meiqi Wang
- Breast Center, Hebei Medical University Fourth Affiliated Hospital, No. 169 Tianshan Street, Shijiazhuang, 050035, China
| | - Ruoyang Li
- Breast Center, Hebei Medical University Fourth Affiliated Hospital, No. 169 Tianshan Street, Shijiazhuang, 050035, China
| | - Zhenchuan Song
- Breast Center, Hebei Medical University Fourth Affiliated Hospital, No. 169 Tianshan Street, Shijiazhuang, 050035, China.
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Cunha Júnior AD, Bragagnoli AC, Costa FO, Carvalheira JBC. Repurposing metformin for the treatment of gastrointestinal cancer. World J Gastroenterol 2021; 27:1883-1904. [PMID: 34007128 PMCID: PMC8108031 DOI: 10.3748/wjg.v27.i17.1883] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/13/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus type 2 and cancer share many risk factors. The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue. Particularly, modulation of inflammation, metabolism, and cell cycle arrest are potential therapeutic cancer targets utilized by metformin to boost the anti-cancer effects of chemotherapy. Studies in vitro and in vivo models have demonstrated the potential of metformin as a chemo- and radiosensitizer, besides its chemopreventive and direct therapeutic activity in digestive system (DS) tumors. Hence, these aspects have been considered in many cancer clinical trials. Case-control and cohort studies and associated meta-analyses have evaluated DS cancer risk and metformin usage, especially in colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Most clinical studies have demonstrated the protective role of metformin in the risk for DS cancers and survival rates. On the other hand, the ability of metformin to enhance the actions of chemotherapy for gastric and biliary cancers is yet to be investigated. This article reviews the current findings on the anti-cancer mechanisms of metformin and its apparatus from pre-clinical and ongoing studies in DS malignancies.
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Affiliation(s)
- Ademar Dantas Cunha Júnior
- Department of Internal Medicine, Division of Oncology, University of Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil
| | | | - Felipe Osório Costa
- Department of Internal Medicine, Division of Oncology, University of Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil
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Singh V, Reddy R, Sinha A, Marturi V, Panditharadyula SS, Bala A. A Review on Phytopharmaceuticals having Concomitant Experimental Anti-diabetic and Anti-cancer Effects as Potential Sources for Targeted Therapies Against Insulin-mediated Breast Cancer Cell Invasion and Migration. CURRENT CANCER THERAPY REVIEWS 2021. [DOI: 10.2174/1573394716999200831113335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Diabetes and breast cancer are pathophysiologically similar and clinically established
diseases that co-exist with a wider complex similar molecular signalling and having a similar set of
risk factors. Insulin plays a pivotal role in the invasion and migration of breast cancer cells. Several
ethnopharmacological evidences shed light on the concomitant anti-diabetic and anti-cancer activity
of medicinal plant and phytochemicals against breast tumors of patients with diabetes. This present
article reviewed the findings on medicinal plants and phytochemicals with concomitant antidiabetic
and anti-cancer effects reported in scientific literature to facilitate the development of dual-
acting therapies against diabetes and breast cancer. The schematic tabular form of published literature
on medicinal plants (63 plants belongs to 45 families) concluded the dynamics of phytochemicals
against diabetes and breast tumors that could be explored further for the discovery of therapies
for controlling of breast cancer cell invasion and migration in patients with diabetes.
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Affiliation(s)
- Vibhavana Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, (NIPER) Hajipur, Export Promotion Industrial Park (EPIP) Hajipur, Bihar 844102, India
| | - Rakesh Reddy
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, (NIPER) Hajipur, Export Promotion Industrial Park (EPIP) Hajipur, Bihar 844102, India
| | - Antarip Sinha
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, (NIPER) Hajipur, Export Promotion Industrial Park (EPIP) Hajipur, Bihar 844102, India
| | - Venkatesh Marturi
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, (NIPER) Hajipur, Export Promotion Industrial Park (EPIP) Hajipur, Bihar 844102, India
| | - Shravani S. Panditharadyula
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, (NIPER) Hajipur, Export Promotion Industrial Park (EPIP) Hajipur, Bihar 844102, India
| | - Asis Bala
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, (NIPER) Hajipur, Export Promotion Industrial Park (EPIP) Hajipur, Bihar 844102, India
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Lee EK, Koo B, Hwangbo Y, Lee YJ, Baek JY, Cha YJ, Kim SY, Sim SH, Lee KS, Park IH, Lee H, Joo J, Go S, Heo SC, Moon MK. Incidence and disease course of new-onset diabetes mellitus in breast and colorectal cancer patients undergoing chemotherapy: A prospective multicenter cohort study. Diabetes Res Clin Pract 2021; 174:108751. [PMID: 33722701 DOI: 10.1016/j.diabres.2021.108751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 02/24/2021] [Accepted: 03/05/2021] [Indexed: 10/21/2022]
Abstract
AIMS To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. METHODS This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. RESULTS Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). CONCLUSIONS DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. TRIAL REGISTRATION ClinicalTrials.gov (NCT03062072).
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Affiliation(s)
- Eun Kyung Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Bokyung Koo
- Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yul Hwangbo
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - You Jin Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Ji Yeon Baek
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Yong Jun Cha
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sun Young Kim
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sung Hoon Sim
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Keun Seok Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - In Hae Park
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Hyewon Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea
| | - Jungnam Joo
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
| | - Sujeong Go
- Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Min Kyong Moon
- Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Dong S, Wang Z, Shen K, Chen X. Metabolic Syndrome and Breast Cancer: Prevalence, Treatment Response, and Prognosis. Front Oncol 2021; 11:629666. [PMID: 33842335 PMCID: PMC8027241 DOI: 10.3389/fonc.2021.629666] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 03/11/2021] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome is a type of multifactorial metabolic disease with the presence of at least three factors: obesity, diabetes mellitus, low high-density lipoprotein, hypertriglyceridemia, and hypertension. Recent studies have shown that metabolic syndrome and its related components exert a significant impact on the initiation, progression, treatment response, and prognosis of breast cancer. Metabolic abnormalities not only increase the disease risk and aggravate tumor progression but also lead to unfavorable treatment responses and more treatment side effects. Moreover, biochemical reactions caused by the imbalance of these metabolic components affect both the host general state and organ-specific tumor microenvironment, resulting in increased rates of recurrence and mortality. Therefore, this review discusses the recent advances in the association of metabolic syndrome and breast cancer, providing potential novel therapeutic targets and intervention strategies to improve breast cancer outcome.
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Affiliation(s)
| | | | - Kunwei Shen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaosong Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Storey S, Zhang Z, Luo X, Von Ah D, Metzger M, Zhang J, Jakka A, Huang K. Association of Comorbid Diabetes With Clinical Outcomes and Healthcare Utilization in Colorectal Cancer Survivors. Oncol Nurs Forum 2021; 48:195-206. [PMID: 33600395 DOI: 10.1188/21.onf.195-206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVES To compare clinical outcomes and healthcare utilization in colorectal cancer (CRC) survivors with and without diabetes. SAMPLE & SETTING CRC survivors (N = 3,287) were identified from a statewide electronic health record database using International Classification of Diseases (ICD) codes. Data were extracted on adults aged 21 years or older with an initial diagnosis of stage II or III CRC with diabetes present before CRC diagnosis or no diagnosis of diabetes (control). METHODS & VARIABLES ICD codes were used to extract diabetes diagnosis and clinical outcome variables. Healthcare utilization was determined by encounter type. Data were analyzed using descriptive statistics, multivariable logistic, and Cox regression. RESULTS CRC survivors with diabetes were more likely to develop anemia and infection than CRC survivors without diabetes. In addition, CRC survivors with diabetes were more likely to utilize emergency resources sooner than CRC survivors without diabetes. IMPLICATIONS FOR NURSING Oncology nurses can facilitate the early identification of high-risk survivor groups, reducing negative clinical outcomes and unnecessarily high healthcare resource utilization in CRC survivors with diabetes.
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Affiliation(s)
| | | | - Xiao Luo
- Indiana University-Purdue University Indianapolis
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Song EY, Swanson J, Patel A, MacDonald M, Aponte A, Ayoubi N, Guerra L, Gonzalez E, Mhaskar R, Mirza AS. Colorectal Cancer Risk Factors and Screening Among the Uninsured of Tampa Bay: A Free Clinic Study. Prev Chronic Dis 2021; 18:E16. [PMID: 33630731 PMCID: PMC7938966 DOI: 10.5888/pcd18.200496] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Introduction Uninsured patients with low socioeconomic status are at high risk for developing colorectal cancer (CRC), and data on risk factors and prevalence of CRC in this population are limited. The purpose of this study was to assess the risk factors for CRC in uninsured patients from free clinics in the Tampa Bay area of Florida. Methods We conducted a retrospective cohort study among patients 50 years or older who were provided service at 9 free clinics in the Tampa Bay area between 2016 and 2018. Demographics, chronic disease characteristics, and screening data were collected via a query of paper and electronic medical records. Results Of the 13,982 patients seen, 5,139 (36.8%) were aged 50 years or older. Most were female (56.8%), non-Hispanic White (41.1%), and unemployed (54.9%). Patients with CRC screening were more likely to be employed compared with patients without CRC screening (54.4% vs 44.4%, P = .01). Within the cohort, 725 (22.7%) patients were active smokers, 771 (29.2%) patients currently consumed alcohol, and 23 patients (0.4%) had a history of inflammatory bowel disease. Patients had a median body mass index of 29.4 (interquartile range, 25.4–34.2) kg/m2, and 1,455 (28.3%) had diabetes. Documented CRC screening was found among 341 (6.6%) patients. Conclusion Uninsured patients had a high prevalence of CRC risk factors but a low reported screening rate for CRC. Free clinics are uniquely positioned to provide patients at high risk for CRC with strategies to decrease their risk and to be screened for CRC.
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Affiliation(s)
- Ethan Y Song
- University of South Florida, Morsani College of Medicine, Tampa, Florida.,University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd, Tampa, FL 33612.
| | - Justin Swanson
- University of South Florida, College of Public Health, Tampa, Florida
| | - Artish Patel
- University of South Florida, Morsani College of Medicine, Tampa, Florida
| | - Madeline MacDonald
- University of South Florida, Morsani College of Medicine, Tampa, Florida
| | | | - Noura Ayoubi
- University of South Florida, Morsani College of Medicine, Tampa, Florida
| | - Lucy Guerra
- USF Morsani College of Medicine, Department of Internal Medicine, Tampa, Florida
| | - Eduardo Gonzalez
- USF Morsani College of Medicine, Department of Family Medicine, Tampa, Florida
| | - Rahul Mhaskar
- USF Morsani College of Medicine, Department of Internal Medicine, Tampa, Florida
| | - Abu-Sayeef Mirza
- USF Morsani College of Medicine, Department of Internal Medicine, Tampa, Florida
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Scully T, Ettela A, LeRoith D, Gallagher EJ. Obesity, Type 2 Diabetes, and Cancer Risk. Front Oncol 2021; 10:615375. [PMID: 33604295 PMCID: PMC7884814 DOI: 10.3389/fonc.2020.615375] [Citation(s) in RCA: 108] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 12/09/2020] [Indexed: 12/12/2022] Open
Abstract
Obesity and type 2 diabetes have both been associated with increased cancer risk and are becoming increasingly prevalent. Metabolic abnormalities such as insulin resistance and dyslipidemia are associated with both obesity and type 2 diabetes and have been implicated in the obesity-cancer relationship. Multiple mechanisms have been proposed to link obesity and diabetes with cancer progression, including an increase in insulin/IGF-1 signaling, lipid and glucose uptake and metabolism, alterations in the profile of cytokines, chemokines, and adipokines, as well as changes in the adipose tissue directly adjacent to the cancer sites. This review aims to summarize and provide an update on the epidemiological and mechanistic evidence linking obesity and type 2 diabetes with cancer, focusing on the roles of insulin, lipids, and adipose tissue.
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Affiliation(s)
- Tiffany Scully
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - Abora Ettela
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - Derek LeRoith
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
- Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - Emily Jane Gallagher
- Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
- Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
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Schairer C, Hablas A, Eldein IAS, Gaafar R, Rais H, Mezlini A, Ayed FB, Ayoub WB, Benider A, Tahri A, Khouchani M, Aboulazm D, Karkouri M, Eissa S, Bastawisy AE, Yehia M, Gadalla SM, Swain SM, Merajver SD, Brown LM, Pfeiffer RM, Soliman AS. Risk factors for inflammatory and non-inflammatory breast cancer in North Africa. Breast Cancer Res Treat 2020; 184:543-558. [PMID: 32876910 PMCID: PMC10440960 DOI: 10.1007/s10549-020-05864-3] [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: 12/24/2019] [Accepted: 08/06/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. METHODS Between 2009 and 2015, we conducted a case-control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups. RESULTS After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types. CONCLUSIONS We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer.
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Affiliation(s)
- Catherine Schairer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | | | | | | | | | | | | | | | | | - Ali Tahri
- Clinique Spécialisée Menara, Marrakech, Morocco
| | | | | | | | | | | | | | - Shahinaz M Gadalla
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Sandra M Swain
- Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, USA
| | | | | | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
- , 9609 Medical Center Drive, Rm 7E142, Bethesda, MD, 20892, USA.
| | - Amr S Soliman
- Medical School of the City University of New York, New York, USA
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Drew DA, Schuck MM, Magicheva-Gupta MV, Stewart KO, Gilpin KK, Miller P, Parziale MP, Pond EN, Takacsi-Nagy O, Zerjav DC, Chin SM, Mackinnon Krems J, Meixell D, Joshi AD, Ma W, Colizzo FP, Carolan PJ, Nishioka NS, Staller K, Richter JM, Khalili H, Gala MK, Garber JJ, Chung DC, Yarze JC, Zukerberg L, Petrucci G, Rocca B, Patrono C, Milne GL, Wang M, Chan AT. Effect of Low-dose and Standard-dose Aspirin on PGE 2 Biosynthesis Among Individuals with Colorectal Adenomas: A Randomized Clinical Trial. Cancer Prev Res (Phila) 2020; 13:877-888. [PMID: 32718943 PMCID: PMC7541643 DOI: 10.1158/1940-6207.capr-20-0216] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 06/04/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022]
Abstract
Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.
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Affiliation(s)
- David A Drew
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Madeline M Schuck
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Marina V Magicheva-Gupta
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kathleen O Stewart
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Katherine K Gilpin
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Patrick Miller
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Melanie P Parziale
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Emily N Pond
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Oliver Takacsi-Nagy
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Dylan C Zerjav
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Samantha M Chin
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Jennifer Mackinnon Krems
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Dana Meixell
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Amit D Joshi
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Wenjie Ma
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Francis P Colizzo
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Peter J Carolan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Norman S Nishioka
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kyle Staller
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - James M Richter
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Hamed Khalili
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Manish K Gala
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - John J Garber
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Daniel C Chung
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Joseph C Yarze
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Lawrence Zukerberg
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Giovanna Petrucci
- Institute of Pharmacology, Catholic University School of Medicine and IRCCS Fondzione Policlinico Gemielli, Rome, Italy
| | - Bianca Rocca
- Institute of Pharmacology, Catholic University School of Medicine and IRCCS Fondzione Policlinico Gemielli, Rome, Italy
| | - Carlo Patrono
- Institute of Pharmacology, Catholic University School of Medicine and IRCCS Fondzione Policlinico Gemielli, Rome, Italy
| | - Ginger L Milne
- Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Andrew T Chan
- Clinical & Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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Kawakita E, Yang F, Kumagai A, Takagaki Y, Kitada M, Yoshitomi Y, Ikeda T, Nakamura Y, Ishigaki Y, Kanasaki K, Koya D. Metformin Mitigates DPP-4 Inhibitor-Induced Breast Cancer Metastasis via Suppression of mTOR Signaling. Mol Cancer Res 2020; 19:61-73. [PMID: 32994182 DOI: 10.1158/1541-7786.mcr-20-0115] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 07/17/2020] [Accepted: 09/24/2020] [Indexed: 11/16/2022]
Abstract
The biological influence of antidiabetic drugs on cancer cells and diabetic cancer patients has not yet been completely elucidated. We reported that a dipeptidyl peptidase (DPP)-4 inhibitor accelerates mammary cancer metastasis by inducing epithelial-mesenchymal transition (EMT) through the CXCL12/CXCR4/mTOR axis. Metformin has been shown to inhibit the mTOR signaling pathway. In this study, we investigated whether metformin mitigates breast cancer metastasis induced by a DPP-4 inhibitor via suppression of mTOR signaling. In cultured mouse mammary and human breast cancer cells, metformin suppressed DPP-4 inhibitor KR62436 (KR)-induced EMT and cell migration via suppression of the mTOR pathway associated with AMPK activation. For the in vivo study, metformin intervention was performed in an allograft 4T1 breast cancer model mouse with or without KR. We also analyzed mice transplanted with shRNA-mediated DPP-4 knockdown 4T1 cells. Treatment with metformin inhibited the lung metastasis of DPP-4-deficient 4T1 mammary tumor cells generated by either KR administration or DPP-4 knockdown. Immunostaining of primary tumors indicated that DPP-4 suppression promoted the expression of EMT-inducing transcription factor Snail through activation of the CXCR4-mediated mTOR/p70S6K pathway in an allograft breast cancer model; metformin abolished this alteration. Metformin treatment did not alter DPP-4-deficiency-induced expression of CXCL12 in either plasma or primary tumors. Our findings suggest that metformin may serve as an antimetastatic agent by mitigating the undesirable effects of DPP-4 inhibitors in patients with certain cancers. IMPLICATIONS: Metformin could combat the detrimental effects of DPP-4 inhibitor on breast cancer metastasis via mTOR suppression, suggesting the potential clinical relevance. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/1/61/F1.large.jpg.
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Affiliation(s)
- Emi Kawakita
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.,Internal Medical 1, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Fan Yang
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Asako Kumagai
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.,Internal Medical 1, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Yuta Takagaki
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Munehiro Kitada
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.,Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Yasuo Yoshitomi
- Department of Biochemistry, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Takayuki Ikeda
- Department of Biochemistry, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Yuka Nakamura
- Division of Molecular and Cell Biology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Yasuhito Ishigaki
- Division of Molecular and Cell Biology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Keizo Kanasaki
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. .,Internal Medical 1, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.,Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan
| | - Daisuke Koya
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. .,Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan
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Kwak S, Kwon S, Lee SY, Yang S, Lee HJ, Lee H, Park JB, Han K, Kim YJ, Kim HK. Differential risk of incident cancer in patients with heart failure: A nationwide population-based cohort study. J Cardiol 2020; 77:231-238. [PMID: 32863081 DOI: 10.1016/j.jjcc.2020.07.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/14/2020] [Accepted: 07/20/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Heart failure (HF) and cancer are currently two leading causes of mortality, and sometimes coexist. However, the relationship between them is not completely elucidated. We aimed to investigate whether patients with HF are predisposed to cancer development using the large Korean National Health Insurance claims database. METHODS This study included 128,441 HF patients without a history of cancer and 642,205 age- and sex-matched individuals with no history of cancer and HF between 1 January 2010 and 31 December 2015. RESULTS During a median follow-up of 4.06 years, 11,808 patients from the HF group and 40,805 participants from the control were newly diagnosed with cancer (cumulative incidence, 9.2% vs. 6.4%, p < 0.0001). Patients with HF presented a higher risk for cancer development compared to controls in multivariable Cox analysis [hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.61-1.68]. The increased risk was consistent for all site-specific cancers. To minimize potential surveillance bias, additional analysis was performed by eliminating participants who developed cancer within the initial 2 years of HF diagnosis (i.e. 2-year lag analysis). In the 2-year lag analysis, the higher risk of overall cancer remained significant in patients with HF (HR 1.09, 95% CI 1.05-1.13), although the association was weaker. Among the site-specific cancers, three types of cancer (lung, liver/biliary/pancreas, and hematologic malignancy) were consistently at higher risk in patients with HF. An exploratory analysis showed that patients with repeated HF hospitalization had a higher risk of cancer development compared to those without, in a pattern of stepwise increases across the three groups [controls vs. HF without re-hospitalization vs. HF with re-hospitalization ≥1; HR (95% CI), 1.00 (reference) vs. 1.55 (1.51-1.59) vs. 1.96 (1.89-2.03), respectively]. CONCLUSIONS Cancer incidence is higher in patients with HF than the general population. Active surveillance of coexisting malignancy needs to be considered in these patients.
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Affiliation(s)
- Soongu Kwak
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Soonil Kwon
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seo-Young Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seokhun Yang
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyun-Jung Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Heesun Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jun-Bean Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Biostatistics, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yong-Jin Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyung-Kwan Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
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Schairer C, Laurent CA, Moy LM, Gierach GL, Caporaso NE, Pfeiffer RM, Kushi LH. Obesity and related conditions and risk of inflammatory breast cancer: a nested case-control study. Breast Cancer Res Treat 2020; 183:467-478. [PMID: 32691376 DOI: 10.1007/s10549-020-05785-1] [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: 04/15/2020] [Accepted: 07/02/2020] [Indexed: 01/06/2023]
Abstract
PURPOSE Inflammatory breast cancer (IBC) is a rare, poorly understood and aggressive tumor. We extended prior findings linking high body mass index (BMI) to substantial increased IBC risk by examining BMI associations before and after adjustment for well-characterized comorbidities using medical record data for diabetes, insulin resistance, and disturbances of cholesterol metabolism in a general community healthcare setting. METHODS We identified 247 incident IBC cases diagnosed at Kaiser Permanente Northern California between 2005 and 2017 and 2470 controls matched 10:1 on birth year and geographic area and with ≥ 13 months of continuous enrollment prior to diagnosis/index date. We assessed exposures from 6 years up to one year prior to the diagnosis/index date, using logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS Before adjustment for comorbidities, ORs (95% CIs) for BMI of 25-< 30, 30-< 35, and ≥ 35 compared to < 25 kg/m2 were 1.5 (0.9-2.3), 2.0 (1.2-3.1), and 2.5 (1.4-4.4), respectively. After adjustment for pre-diabetes/diabetes, HDL-C and triglyceride levels, and dyslipidemia, corresponding ORs were 1.3 (0.8-2.1), 1.6 (0.9-2.9), and 1.9 (1.0-3.5). The OR for HDL-C levels < 50 mg/dL compared to ≥ 65 mg/dL was 2.0 (1.2-3.3) in the adjusted model. In a separate model the OR for a triglyceride/HDL-C ratio ≥ 2.50 compared to < 1.62 was 1.7 (1.1-2.8) after adjustment for BMI, pre-diabetes/diabetes, and dyslipidemia. Results did not differ significantly by estrogen receptor status. CONCLUSIONS Obesity and measures of insulin resistance independently increased IBC risk as did obesity and low HDL-C levels. These findings, if confirmed, have implications for IBC prevention.
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Affiliation(s)
- Catherine Schairer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rm 7E142, Bethesda, MD, 20892, USA
| | - Cecile A Laurent
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Lisa M Moy
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Gretchen L Gierach
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rm 7E142, Bethesda, MD, 20892, USA
| | - Neil E Caporaso
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rm 7E142, Bethesda, MD, 20892, USA
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rm 7E142, Bethesda, MD, 20892, USA.
| | - Lawrence H Kushi
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
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Abstract
Debate is ongoing regarding the relationship between type 2 diabetes and cancer, and the pathways linking the two are incompletely understood. Some posit that the relationship hinges on a common predisposing factor such as obesity, insulin resistance, or chronic inflammation that increases the risk of cancer independently. Others speculate that diabetes acts as an independent risk factor for cancer because of other molecular pathways and interactions. Additionally, antidiabetic medications have been associated with changes in cancer risk. This review presents a summary of the latest studies and data concerning the relationships among type 2 diabetes, antidiabetic medications, cancer risk, and cancer prognosis.
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