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

Abstract

Introduction: Excess alcohol consumption is associated with increased risk of colorectal cancer (CRC), 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 (PRS) based on 140 CRC-related loci with findings of colorectal neoplasia among 4,662 participants in the German screening colonoscopy program. Analyses were conducted by multiple logistic regression. We determined genetic risk equivalents (GREs) to quantify the effect of alcohol consumption in terms of the difference in PRS conveying equivalent risk.

Results: Moderate and high (12-<25 and ≥25 g/day) alcohol consumption was associated with increased risk of advanced colorectal neoplasia (aOR [95% CI]: 1.28 [1.03-1.58] and 1.44 [1.14-1.81], respectively), while associations with any colorectal neoplasia were weaker. No significant interactions between alcohol consumption and PRS were observed. Participants with high alcohol consumption in the highest PRS tertile had a 3.4-fold increased risk of advanced neoplasia compared to those with low or no alcohol consumption in the lowest PRS tertile. The estimated impact of high alcohol consumption on the risk of advanced neoplasia was equivalent to the risk increase by a 26 percentiles higher PRS (GRE 26, 95% CI 9-44).

Conclusion: High alcohol consumption and PRS both 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.