Abstract LB-249: Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial

BACKGROUND Marine omega-3 fatty acid (MO3FA) has been suggested to protect against colorectal cancer. However, the chemopreventive effect of MO3FA on precursors of colorectal cancer remains unclear. METHODS We assessed the effect of MO3FA supplementation on risk of conventional adenomas and serrated polyps, the two distinct subtypes of precursors of colorectal cancer, within the VITamin D and OmegA-3 TriaL (VITAL), a randomized, placebo-controlled, two-by-two factorial trial of MO3FA (1 g per day [460 mg EPA and 380 mg DHA]) and vitamin D3 (2000 IU per day) supplements among 25,871 Americans aged 50 years or older (including 5,106 blacks). Although regular screening endoscopy was not protocol-mandated during the study period, prior colonoscopy/sigmoidoscopy and other risk factors were well balanced by treatment group at baseline. When participants reported a diagnosis of polyp on the annual follow-up questionnaire, we requested permission to obtain endoscopic and pathologic records to confirm the diagnosis and extract the histopathologic information. Serrated polyps included hyperplastic polyps and mixed/serrated adenomas (traditional and sessile types). We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) in relation to MO3FA treatment using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. We also performed subgroup analyses according to polyp features and participants’ characteristics. RESULTS During a median follow-up of 5.3 years, we documented 296 cases of colorectal adenomas in the intervention group and 306 in the control groups (multivariable OR=0.97, 95% CI, 0.83-1.14); and 178 and 170 cases of serrated polyps in the two groups, respectively (OR=1.05, 95% CI, 0.85-1.30). Similar null association was found for advanced adenomas (advanced histology or ≥10 mm) or high-risk serrated polyps (located in the proximal colon or ≥10 mm), or polyp subgroups according to size, location, multiplicity, or histology. When stratified by race/ethnicity, we found that MO3FA treatment was associated with lower risk of adenomas (OR=0.53, 95% CI, 0.31-0.91) and serrated polyps (OR=0.54, 95% CI, 0.27-1.10) in African Americans, whereas no association was found in non-Hispanic whites or other racial/ethnic groups (P for interaction=0.06 for adenomas and 0.15 for serrated polyps). No interaction was detected with other demographic factors, colorectal cancer risk factors, endoscopic use, baseline fish intake, or plasma MO3FA levels. CONCLUSIONS Supplementation with marine omega-3 fatty acids at a dose of 1 g per day was not associated with risk of colorectal premalignant lesions. A potential benefit among African Americans requires further confirmation. Citation Format: Mingyang Song, I-Min Lee, JoAnn E. Manson, Julie E. Buring, Rimma Dushkes, David Gordon, Joseph Walter, Kana Wu, Andrew T. Chan, Shuji Ogino, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward L. Giovannucci. Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-249.