Abstract 1197: Association of increasing alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Introduction: Recent alcohol drinking has been associated with higher colorectal cancer (CRC) risk. However, research on lifetime alcohol drinking in relation to colorectal adenoma (CRC precursor) and CRC risk is limited. We aimed to estimate the association of average lifetime alcohol drinking and change in alcohol consumption over adulthood with incident colorectal adenoma and cancer. Methods: U.S. adults enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were asked about alcohol intake during four age periods (18-24, 25-39, 40-54, and ≥55 years) as part of a dietary history questionnaire (DHQ). Participants were also asked about alcohol consumption in the year prior to the DHQ (reflecting current drinking). Average lifetime alcohol intake was calculated as average drinks per week from early adulthood (age 18-24) until age at DHQ completion (median of 65 years). Change in alcohol intake was defined as the difference between alcohol intake at the DHQ and age 18-24. Incident adenomas (n=807, including 196 advanced adenomas) were defined in the screening arm based on a negative baseline trial screen and a positive follow-up trial screen 3 or 5 years later; controls (n=11, 446) were defined based on negative baseline and follow-up screens. CRC incidence (n=1, 679) was defined based on 20 years of cancer follow-up in both trial arms. Multivariable-adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for incident adenoma. Multivariable-adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% CI for CRC. Models adjusted for a number of potential confounders including demographic factors, body mass index, family history of CRC, and various dietary factors. P-values for interaction between alcohol intake and sex were computed using likelihood ratio tests comparing models with and without the interaction terms. Results: Increasing alcohol intake by 1 drink/day every 10 years was associated with higher risk of adenoma (OR=1.19, CI: 1.02-1.39), advanced adenoma (OR=1.41, CI: 1.11-1.79), and CRC (HR=1.11, CI: 0.99-1.24). Among men, drinking ≥14 drinks/week, compared to <1 drink/week, throughout adulthood was positively associated with risk of advanced adenoma (OR=1.83, CI: 0.95-3.50) as well as rectal (HR=1.80, CI: 1.03-3.13) and distal colon (HR=1.54, CI: 0.98-2.42) but not proximal colon (HR=0.96, CI: 0.71-1.31) cancer. Associations tended to be less pronounced among women, but with limited case numbers, we found no evidence of significant effect modification by sex (p-interaction>0.05). Conclusions: Our study suggests that increasing alcohol intake over the lifetime and higher average lifetime alcohol drinking is associated with a higher risk of advanced colorectal adenoma and CRC. Citation Format: Caitlin P. O'Connell, Sonja I. Berndt, Kenechukwu Chudy-Onwugaje, Andrew T. Kunzmann, Wen-Yi Huang, Kathryn Hughes Barry, Erikka Loftfield. Association of increasing alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1): nr 1197.