Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk

The authors of a study published in eClinicalMedicine state that evidence is lacking on the impact of alcohol consumption on colorectal cancer (CRC) risk (overall and by age at diagnosis) by polygenic risk score (PRS) levels, and it is unclear how the magnitude of CRC risk associated with alcohol consumption compares to the magnitude of genetically determined risk.
The association between alcohol consumption and colorectal cancer (CRC) was assessed across PRS levels based on 140 CRC-related loci among 5,104 CRC cases and 4,131 controls from a large population-based case-control study. The effects for alcohol consumption and PRS on CRC risk were examined. Specific analyses were conducted for early-onset CRC (EOCRC, <55 years) and late-onset CRC (LOCRC, ≥55 years).
High alcohol consumption, and to a lower extent, also alcohol abstinence were associated with increased CRC risk. Compared to low alcohol consumption (0·1-<25 g/d), lifetime average alcohol consumption ≥25 g/d was more strongly associated with EOCRC [odds ratio (OR) 1·8, 95% confidence interval (CI) 1·2-2·8] than with LOCRC risk (OR 1·3, 95% CI 1·1-1·4). Interactions between alcohol consumption and PRS did not reach statistical significance for either EOCRC or LOCRC risk. The estimated impact of high lifetime alcohol consumption on EOCRC was equivalent to the effect of having 47 percentiles higher PRS (GRE 47, 95% CI 12-82), stronger than the impact on LOCRC (GRE 18, 95% CI 8-29).
The authors say that excessive alcohol use was strongly associated with EOCRC risk, independent of PRS levels. Abstaining from heavy drinking could reduce risk for CRC, in particular for EOCRC to an extent that would be equivalent to having a much lower genetically determined risk.
Source: Chen X, Li H, Guo F, Hoffmeister M, Brenner H. Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk. EClinicalMedicine. 2022 May 20;49:101460..