- Gastrointestinal Cancer
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Association between ALDH2 and ADH1B Polymorphisms and the Risk for Colorectal Cancer in Koreans
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Chang Kyun Choi, Min-Ho Shin, Sang-Hee Cho, Hye-Yeon Kim, Wei Zheng, Jirong Long, Sun-Seog Kweon
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Cancer Res Treat. 2021;53(3):754-762. Published online December 24, 2020
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DOI: https://doi.org/10.4143/crt.2020.478
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Abstract
PDFPubReaderePub
- Purpose
Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk.
Materials and Methods The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses.
Results Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63).
Conclusion Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.
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Citations
Citations to this article as recorded by
- Potentially functional genetic variants in interferon regulatory factor family genes are associated with colorectal cancer survival
Xiaoxia Tong, Chenghui Li, Li Ma, Di Wu, Yonglei Liu, Liqin Zhao, Mengyun Wang Molecular Carcinogenesis.2024; 63(9): 1669. CrossRef - Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol‐related disorder and cancer
Ting‐Gang Chang, Ting‐Ting Yen, Chia‐Yi Wei, Tzu‐Hung Hsiao, I‐Chieh Chen Cancer Medicine.2023; 12(1): 747. CrossRef - TP73-AS1 rs3737589 Polymorphism is Associated With the Clinical Stage of Colorectal Cancer
Yichang Gao, Shulong Zhang, Xueren Gao, Vijaya Anand Evidence-Based Complementary and Alternative Medicine.2023;[Epub] CrossRef - Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods
Ting-ting Liu, De-tao Yin, Nan Wang, Na Li, Gang Dong, Meng-fan Peng Frontiers in Endocrinology.2023;[Epub] CrossRef - No association between genetically predicted C-reactive protein levels and colorectal cancer survival in Korean: two-sample Mendelian randomization analysis
Chang Kyun Choi, Jung-Ho Yang, Min-Ho Shin, Sang-Hee Cho, Sun-Seog Kweon Epidemiology and Health.2023; 45: e2023039. CrossRef - Genetically determined alcohol consumption and cancer risk in Korea
Keum Ji Jung, Ji Woo Baek, Sang Yop Shin, Sun Ha Jee Epidemiology and Health.2023; 45: e2023077. CrossRef - Dysregulated Expression of Three Genes in Colorectal Cancer Stratifies Patients into Three Risk Groups
Alba Rodriguez, Luís Antonio Corchete, José Antonio Alcazar, Juan Carlos Montero, Marta Rodriguez, Luis Miguel Chinchilla-Tábora, Rosario Vidal Tocino, Carlos Moyano, Saray Muñoz-Bravo, José María Sayagués, Mar Abad Cancers.2022; 14(17): 4076. CrossRef - Alcohol metabolism genes and risks of site‐specific cancers in Chinese adults: An 11‐year prospective study
Pek Kei Im, Ling Yang, Christiana Kartsonaki, Yiping Chen, Yu Guo, Huaidong Du, Kuang Lin, Rene Kerosi, Alex Hacker, Jingchao Liu, Canqing Yu, Jun Lv, Robin G. Walters, Liming Li, Zhengming Chen, Iona Y. Millwood International Journal of Cancer.2022; 150(10): 1627. CrossRef - The Roles of Drug Metabolism-Related ADH1B in Immune Regulation and Therapeutic Response of Ovarian Cancer
Zhijie Xu, Bi Peng, Fanhua Kang, Wenqin Zhang, Muzhang Xiao, Jianbo Li, Qianhui Hong, Yuan Cai, Wei Liu, Yuanliang Yan, Jinwu Peng Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef - Alcoholic liver disease: a new insight into the pathogenesis of liver disease
Seol Hee Park, Young-Sun Lee, Jaemin Sim, Seonkyung Seo, Wonhyo Seo Archives of Pharmacal Research.2022; 45(7): 447. CrossRef - MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population
Xu Liu, Kelaier Yang, Zhangfu Li, Jikui Liu International Journal of General Medicine.2022; Volume 15: 6009. CrossRef - ALDH2 gene rs671 G > a polymorphism and the risk of colorectal cancer: A hospital‐based study
Zhuoxin Zhang, Yijin Chen, Qingqing Zhuo, Changqing Deng, Yang Yang, Wen Luo, Shixun Lai, Hui Rao Journal of Clinical Laboratory Analysis.2022;[Epub] CrossRef
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Diabetes Medication Use in Association with Survival among Patients of Breast, Colorectal, Lung, or Gastric Cancer
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Michelle L. Baglia, Yong Cui, Tao Zheng, Gong Yang, Honglan Li, Mingrong You, Liling Xu, Harvey Murff, Yu-Tang Gao, Wei Zheng, Yong-Bing Xiang, Xiao-Ou Shu
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Cancer Res Treat. 2019;51(2):538-546. Published online July 2, 2018
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DOI: https://doi.org/10.4143/crt.2017.591
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival.
Materials and Methods
The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models.
Results
After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival.
Conclusion
Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.
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