Abstract 799: Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study

Abstract

Abstract Previously, we reported associations between breast cancer (BC) risk and tuna intake in non-Hispanic White (NHW) and Hispanic women, and processed meat intake among Hispanic women only. We also reported associations with SNPs in genes involved in the Convergence of Hormones, Inflammation, and Energy-related Factors (CHIEF) network. Given the multifactorial nature of BC etiology, we tested for interactions (GxE) between meat/fish intake and SNPs in selected CHIEF pathways using a set-based method that aggregates SNPs into groups for GxE association testing.The study population included Hispanic (1046 cases, 1331 controls) and NHW (1234 cases, 1468 controls) women from two US population-based case-control studies that are part of the Breast Cancer Health Disparities Study. Harmonized meat intake variables were dichotomized, and include red meat, processed meat, poultry, fish, and tuna. 734 SNPs were grouped into 107 genes based on loci. Genes were further grouped into 7 pathways based on biological function: CHIEF core, ALOX/COX, Interleukins, JAK/STAT/SOC, TLR/TNF, MAPK, and TGF-â. We performed the analysis in a top-down fashion, sequentially testing for interactions between meat/fish intake and pathways, genes within pathways, and SNPs within genes. To test pathways and genes, we used a set-based GxE approach that extends the adaptive rank truncated product (ARTP), and to test individual SNPs we used logistic regression. At gene and SNP level analyses, we applied Bonferroni corrections for the number of genes or SNPs tested. Analyses were stratified by ethnicity. Models were adjusted for study, age, education, menopausal status, family history of breast cancer, parity, body mass index, physical activity, education, intake of alcohol, fiber, calories, fat, carbohydrates, proteins, and genetic ancestry. We report results that showed statistically significant interactions at both pathway and gene levels. Analyses were conducted using the R programming language. Among NHW women, pathway-level analyses using ARTP identified an interaction between poultry intake and the interleukin/cytokine pathway, which was driven by the IL17A gene (2 SNPs); poultry intake was inversely associated with BC risk among carriers of the minor alleles in this gene. Among Hispanics, ARTP analyses identified an interaction between tuna intake and total fish intake and the Jak/Stat/SOC pathway, which was driven by STAT5A (tuna: 2 SNPs) and STAT5B (total fish and tuna: 3 SNPs). The positive associations between fish or tuna and BC risk were restricted to carriers of minor alleles in these two genes. Overall, our findings suggest a role for poultry and fish intake in chronic inflammation and tumor growth promotion in breast carcinogenesis and highlight specific genes that may play roles in these carcinogenic pathways. Citation Format: Andre E. Kim, Juan Pablo Lewinger, Shirong Zhang, Roger K. Wolff, Laura Fejerman, Esther M. John, Gabriela Torres-Mejia, Jennifer S. Herrick, Stephanie D. Boone, Avonne E. Connor, Lisa M. Hines, Kathy B. Baumgartner, Anna Giuliano, Martha L. Slattery, Mariana C. Stern. Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 799.