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

Abstract

AimTo explore the association 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 an East Chinese population.MethodsWe 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.ResultsWe 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 post-menopausal women.ConclusionsNFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China.

Association of polymorphisms in interleukin-8 gene with cancer risk: a meta-analysis of 22 case&ndash;control studies

“… 38 In addition, previous studies have confirmed that A allele is associated with an increased risk of many cancer types. 19 , 20 , 39 Recently, several meta-analysis have been conducted and have identified that rs4073 polymorphism was related to an increased risk of overall cancers and potentially offered an evidence-based medical certificate to investigate cancer risk. 35 , 40 , 41 Considering that a large number of meta-analyses concentrated on IL-8 rs4073 polymorphism and cancer risk were performed, we focus only on several other polymorphisms in IL-8 and cancer risk.…”

“…Wang et al 19 identified that no association of rs4073, rs2227306, −353A/T, and +678T/C polymorphisms in IL-8 gene and HCC risk was revealed in the Chinese population. Then, Wang et al 39 performed a case–control study enrolling 474 breast cancer patients and 501 female nontumor controls and identified that TT genotype of IL-8 rs4073 polymorphism has a significantly reduced risk of breast cancer (TT: OR =0.48, 95% CI =0.33–0.72, P <0.001). In another study, Liu et al 20 enrolled 270 patients with oral squamous cell carcinoma and 350 healthy controls, and their results demonstrated that four polymorphisms (rs4073, rs2227306, +1633C/T, and +276A/T) were not related to the risk of oral cancer or clinic pathological characteristics.…”

Association of tumor necrosis factor α −308G/A and interleukin-6 −174G/C gene polymorphism with pneumonia-induced sepsis

“…Although there is evidence suggesting a relationship between TNF − 308, IL-6 rs1800795, and sepsis risk, other researchers could not find a consistent association between the SNPs and the risks of sepsis and outcomes [14]. Moreover, many previous studies reported a higher prevalence of IL-6 rs1800795 and rs1800629 polymorphisms and a connection with a variety of diseases in the Chinese Han population [15][16][17][18].…”

Association between higher expression of interleukin-8 (IL-8) and haplotype −353A/−251A/+678T of IL-8 gene with preeclampsia

“…Polymorphisms of the IL-8 gene have been implicated in several human diseases. For instance, the +781C/T and −352A/T polymorphisms of IL-8 gene are related to cancer development, [10,11] while the 4073A/T polymorphism is associated with myocardial infarction. [12] Interestingly, increasing evidence has suggested that polymorphisms of inflammation-related genes may be associated with PE development, such as tumor necrosis factor-α, IL-10, and IL1A.…”