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

Abstract

Aim To explore the association of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA c.-949C > T (rs2233406), IL-8 c.-352-A > 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 an East Chinese population. Methods We conducted a case-control study including 975 study participants (474 breast cancer patients and 501 female controls without cancer) and genotyped the polymorphisms employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to assess the association of the polymorphisms with breast cancer risk. Results We found that the ins/del and del/del genotypes of NFKB1 polymorphism and TT genotype of IL-10 polymorphism significantly increased breast cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P = 0.001; NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P < 0.001; IL-10 TT OR 2.36, 95% CI 1.58-3.52, P < 0.001). On the other hand, the TT genotype of IL-8 polymorphism, GA and AA genotypes of TNF c.-418G > A polymorphism, and GA genotype of TNF c.- 488G > A polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI 0.33-0.72, P < 0.001; TNF c.- 418 GA OR 0.58, 95% CI 0.41-0.80, P = 0.001; TNF c.-418 AA OR 0.38, 95% CI 0.14-0.98, P = 0.044; TNF c.-488 GA OR 0.68, 95% CI 0.48-0.96, P = 0.029). When stratified by menopausal status, the CT genotype of NFKBIA polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63, 95% CI 0.40-0.99, P =, 043), but not among postmenopausal women. Conclusions NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China.