Alcohol consumption, polygenic risk score, and the risk of colorectal neoplasia

Abstract Background Excess alcohol consumption is associated with increased risk of colorectal cancer, but the evidence on the individual and joint effects of alcohol consumption and genetic risk on the occurrence of various stages of colorectal carcinogenesis is limited. Methods We evaluated the associations of alcohol consumption and a polygenic risk score based on 140 colorectal cancer related loci with findings of colorectal neoplasia among 4662 participants in the German screening colonoscopy program. Analyses were conducted by multiple logistic regression. We determined genetic risk equivalents to quantify the effect of alcohol consumption in terms of the difference in polygenic risk score conveying equivalent risk. Results Moderate and high (12 to <25 g/d and ≥25 g/d) alcohol consumption was associated with increased risk of advanced colorectal neoplasia (adjusted odds ratio = 1.28, 95% CI = 1.03 to 1.58, and adjusted odds ratio = 1.44, 95% CI = 1.14 to 1.81, respectively), while associations with any colorectal neoplasia were weaker. No significant interactions between alcohol consumption and polygenic risk score were observed. Participants with high alcohol consumption in the highest polygenic risk score tertile had a 3.4-fold increased risk of advanced neoplasia compared with individuals with low or no alcohol consumption in the lowest polygenic risk score tertile. The estimated impact of high alcohol consumption on the risk of advanced neoplasia was equivalent to the risk increase by a 26-percentile-higher polygenic risk score (genetic risk equivalent = 26, 95% CI = 9 to 44). Conclusion High alcohol consumption and polygenic risk score have a major impact on the risk of advanced colorectal neoplasia. The estimated preventive impact of avoiding high alcohol consumption is as strong as the impact of having a substantially lower polygenic risk.