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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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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