Abstract 1323: Genome-wide association study of energy intake and its relationship to prostate cancer

Abstract

Abstract Background/Objectives: Previous studies suggested that high energy intake may increase the risk of prostate cancer. However, the mechanisms remain unclear. No genome-wide association studies (GWAS) have been conducted to detect the genetic variations in total energy intake. We aimed to identify genetic variants associated with total energy intake in men and women, and to determine the association between previously identified prostate cancer susceptibility loci and total energy intake. Methods: We conducted a genome-wide study using combined GWAS data from 12,031 European-ancestry women and 6,743 European-ancestry men from the Nurses’ Health Study, Nurses’ Health Study II, Health Professionals Follow-up Study, and Physician’s Health Study. Total energy intake was measured through validated food-frequency questionnaires. Missing genotypes were imputed using MACH with 1000 Genomes Project ALL Phase I Integrated Release Version 3 Haplotypes as the reference panel. We stratified by sex and adjusted for age, weight, height, physical activity and three principal components accounting for subpopulation structure. Meta-analysis based on p-values across sex was implemented. SNP set analyses, including a weighted fixed-effects (Mendelian randomization, MR) and an unweighted random-effects approach (METASOFT), were used to test the association between prostate cancer risk loci and total energy intake using summary statistics of total energy intake from the combined GWAS and the summary statistics for genome-wide significant SNPs (NSNPs = 104) from a GWAS of prostate cancer in 43,303 cases and 43,737 controls [Al Olama (2014) Nat Genet]. Results: Three SNPs near gene ANKRD33 were genome-wide significantly (P < 5.0×10-8) associated with the increase in total energy intake among men (rs10876214 [P = 5.81×10-10], rs9669605 [P = 1.46×10-8], and rs10783478 [P = 2.42×10-8]). No significant genome-wide association was found in women or the meta-analysis combining men and women. SNP set analyses did not find a statistically significant association between established prostate cancer SNPs and energy intake (PMR = 0.11 and PMETASOFT = 0.09, respectively). Conclusions: We identified three significant SNPs near gene ANKRD33 associated with increased total energy intake among men. Genetic alleles related to risk of prostate cancer were not associated with total energy intake. Larger GWAS studies of total energy intake are warranted to explore the genetic basis of energy intake, including possible differences between men and women, and the association between total energy intake, prostate cancer, and other cancers and chronic diseases. Citation Format: Lai Jiang, Peter Kraft, Kathryn M. Wilson. Genome-wide association study of energy intake and its relationship to prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1323. doi:10.1158/1538-7445.AM2017-1323