Abstract 1454: Interaction of obesity loci with energy intake and physical activity on the risk of colorectal cancer: Evidence from UK Biobank

Abstract Colorectal cancer is one of the common cancers worldwide. Obesity and physical activity are well-established risk factors for colorectal cancer. Studies have shown that as a consequence of energy metabolism, imbalance between energy intake and physical activity can lead to obesity. In order to precisely examine the close interrelationship between obesity, energy intake, and physical activity, we conducted a genome-wide interaction study of obesity with energy intake and physical activity. We also evaluated the interaction between obesity susceptibility loci with energy intake and physical activity for colorectal cancer using the nested case-control design. We analyzed data on participants in the UK Biobank. Genome-wide interaction analyses of obesity with energy intake and physical activity was performed on 65,514 and 250,369 participants who have information on genotype, body mass index, and energy intake/physical activity, respectively. We assessed the effect of obesity loci in the participants comprised 3523 colorectal cancer cases and 10,522 matched controls. The logistic regression model was used for finding obesity loci under a p-value threshold of 10-4. Odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer were estimated using a conditional logistic regression model. We found 21 loci and 44 loci of obesity with energy intake and physical activity, respectively. We also observed significant interaction of obesity loci with energy intake and physical activity for colorectal cancer. The obesity loci interacting with energy intake, including rs10828896 and rs7099260, were significantly interacted with physical activity for colorectal cancer. Rs426345 and rs12551684, which were the obesity loci interacting with physical activity, were significantly interacted with energy intake for colorectal cancer. The results of this study may provide evidence for bioenergetics in colorectal cancer carcinogenesis. Citation Format: Sooyoung Cho, Aesun Shin. Interaction of obesity loci with energy intake and physical activity on the risk of colorectal cancer: Evidence from UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1454.