Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: The breast cancer health disparities study

Abstract

Interleukins are key regulators of immune response. Genetic variation in interleukin genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis, and regulation of inflammatory process. We examined 16 interleukin genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (PARTP=0.0006), for women with low NA ancestry (PARTP=0.01), for pre-menopausal women (PARTP=0.02), for ER+/PR+ tumors (PARTP=0.03), and ER-/PRtumors (PARTP=0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6, IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R, IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with pre-menopausal breast cancer risk (IL1A, IL1B, IL2, and IL3). IL4, IL6R, IL8, and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.