Abstract 4614: Genome-wide association analysis of pro-inflammatory cytokines and gene-lifestyle interaction for invasive breast cancer risk: The WHI Database for Genotypes and Phenotypes Study

Abstract

Abstract Purpose: Pro-inflammatory biomarkers and their genetic variants may interact with obesity and obesity-related lifestyle factors, influencing breast cancer risk in postmenopausal women, but the interrelated metabolic pathways are incompletely understood. Methods: We used data from the Women's Health Initiative Database for Genotypes and Phenotypes Study including 16,088 postmenopausal women, a population highly susceptible to obesity and increased risk for breast cancer. We conducted a genome-wide association (GWA) analysis in two steps: 1) with six GWA substudies, GWA meta-analysis of pro-inflammatory cytokines (Interleukin-6 [IL-6] and C-reactive protein [CRP]) for their gene-lifestyle interactions and 2) test for the association between identified single-nucleotide polymorphisms (SNPs) at the genome-wide level and breast cancer risk. Results: In women overall and stratified by obesity status (body mass index, waist circumference, and waist-to-hip circumference) and obesity-related lifestyle factors (physical activity and high fat-diet), 88 loci were associated with pro-inflammatory phenotypes at genome-wide significance: 3 associated with IL-6 (1 index SNP in MAPK1 and 1 independent SNP in DEC1); 85 with CRP (3 index SNPs in CRP/CRPP1/HNF1A and 2 SNPs in APOE/APOC1, independently). Of those, 27 loci had significantly increased risk for breast cancer. Conclusions: We found a number of novel genetic markers in relation to pro-inflammatory phenotypes, which interacted with obesity and related lifestyle factors. A substantial proportion of those SNPs' susceptibility influences breast cancer risk in the identical subgroup populations. Our findings may contribute to improved prediction accuracy for cancer and suggest intervention strategies for women who carry the risk genotypes, eventually reducing breast cancer risk. Citation Format: Su Yon Jung, Peter Scott, Sihao Han, Matteo Pellegrini, Jeanette Papp, Eric Sobel, Herbert Yu, Zuo-Feng Zhang. Genome-wide association analysis of pro-inflammatory cytokines and gene-lifestyle interaction for invasive breast cancer risk: The WHI Database for Genotypes and Phenotypes Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4614.