Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk

Breast cancer is the most frequent form of cancer and leading cause of cancer-related deaths among women around the world (1). The cancer accounts for almost one quarter of new cancer cases annually (2), and the incidence continues to increase rapidly, both in China and worldwide (3). Although it has been well-established that breast carcinogenesis is a result of the complex interactions between multiple environmental and genetic factors, the mechanisms of the oncogenesis at the molecular level remain poorly understood. Genetic factors can serve as a susceptibility variable for breast cancer development, and their identification can help to reduce the incidence of breast cancer (4). However, several breast cancer susceptibility genes identified so far, such as BRCA1 and BRCA2, account for only less than 5% of the total breast cancer incidence (5). Single nucleotide polymorphisms (SNPs) have been extensively investigated for their associations with the risk of various cancers (6-11). As inflammation is caused by a molecular network underlying breast carcinogenesis (12), we propose that SNPs within inflammatory response genes could modify breast cancer predisposition risk. The associations of various inflammatory response gene polymorphisms with breast cancer risk in the Chinese population, especially the East Chinese population, have been understudied. In the current study, we investigated the associations of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA c.-949C>T (rs2233406), IL-8 c.-352A>T (rs4073), IL-10 c.-854T>C (rs1800871), TNF c.-418G>A (rs361525), and TNF c.-488G>A (rs1800629) polymorphisms with breast cancer risk in East China. Since all these polymorphisms are located in the promoter region, they could affect the transcriptional activity of the gene, resulting in enhanced or reduced cDNA, and eventually protein levels, among their carriers (6,7,13). In addition, despite the relatively well established associations of the polymorphisms with cancer risks in other populations (6-9), little is known about their association with breast cancer risk in East China population, which further motivated us to undertake this research.