LAUSR

A total of 13 cancers are known to be strongly associated with obesity. The purpose of this study was to examine the association between a composite genotype risk score (GRS) for high body mass index (BMI) and the odds of obesity-related cancer. A nested case-control study was created within the Pennington Center Longitudinal Study, an ongoing prospective cohort study of the effects of obesity and lifestyle factors on the development of chronic diseases and premature mortality in Black and White Americans. A total of 459 participants developed an obesity-related cancer, and after stratification by sex and race, incidence density sampling was applied to select matched control participants (2:1) of the same age as cases (± 2 y). After deletion of participants with missing data, the analytic sample included 1242 participants (435 cases;136 Black, 299 White). A BMI GRS was derived using 21 single nucleotide polymorphisms (SNPs) with consistent evidence of association from the literature and which showed concordant associations in effect size and direction in our cohort. The GRS score was computed by summing the number of BMI risk alleles. In a model including age, race, sex, exam year and smoking as covariates, the BMI GRS was significantly associated with obesity-related cancer [odds ratio (OR): 1.18; 95% confidence interval: 1.04, 1.34; p=0.01]. Further adjustment for BMI did not change the association [1.20; 1,06-1.36; p=0.004]. In conclusion, the BMI GRS appears to provide added value in identifying obesity-related cancer risk, even after adjustment for BMI. Future studies are required to validate these results and better delineate the phenotypic and genetic contributions of BMI to obesity-related cancer risk. Citation Format: Peter T. Katzmarzyk, Shengping Yang, Justin C. Brown, Emily F. Mire, Jovanny Zabaleta. Body mass index genetic risk score and obesity related cancer risk in Black and White adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1977.