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Cancer Research and Treatment > Epub ahead of print
doi: https://doi.org/10.4143/crt.2020.478    [Epub ahead of print]
Association between ALDH2 and ADH1B Polymorphisms and the Risk for Colorectal Cancer in Koreans
Chang Kyun Choi1, Min-Ho Shin1, Sang-Hee Cho2, Hye-Yeon Kim3, Wei Zheng4, Jirong Long4, Sun-Seog Kweon1
1Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea
2Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
3Gwangju-Jeonnam Regional Cardiocerebrovascular Center, Chonnam National University Hospital, Gwangju, Korea
4Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
Correspondence  Sun-Seog Kweon ,Tel: 82-61-379-2624, Fax: 82-61-379-7880, Email: ujingogo@paran.com
Received: May 19, 2020;  Accepted: December 23, 2020.  Published online: December 24, 2020.
ABSTRACT
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.
Key words: Alcohol, Alcohol dehydrogenase 2, Aldehyde dehydrogenase 2, Colorectal neoplasm
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