The Association of TNF-α Promoter Polymorphisms with Genetic Susceptibility to Cervical Cancer in a Chinese Han Population

Abstract

Background: The tumour necrosis factor-α (TNF-α) gene plays an important role in the host immune response, which will influence the development and clearance of cancer. Polymorphism of the TNF-α promoter region is considered to influence its transcription and be a risk factor for tumorigenesis. In the current study, we evaluated the role of TNF-α promoter region polymorphisms in susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). Methods: A total of 2732 subjects, including 1173 healthy controls, 579 patients with CIN and 980 patients with CC in a Chinese Han population, were selected for the current study. Five SNPs in the TNF-α promoter, rs1799964 (−1031 C>T), rs1800630 (−863 A>C), rs1799724 (−857 C>T), rs1800629 (−308 A>G) and rs361525 (−238 A>G), were selected and genotyped using TaqMan Assays. The association of these SNPs with CIN and cervical cancer was evaluated among healthy controls, CIN and CC patients. Results: The frequency distribution of rs1800629 and rs361525 alleles was significantly different between the CC group and the control group (P=0.009 and P=0.002). The rs1800629 A allele was found to be a protective factor for CC (OR=0.72; 95% CI=0.56–0.92). The rs361525 A allele was found to be a risk factor for CC (OR=1.69; 95% CI=1.21–2.38). After pathological subtyping of CC, the allele distribution of rs1800629 and rs361525 were both significantly different between the cervical squamous cell carcinoma and control groups (P=0.002 and P<0.001). The rs1800629 A allele was protective factor for cervical squamous cell carcinoma (OR=0.66; 95% CI=0.50–0.86). The rs361525 A allele was a risk factor for cervical squamous cell carcinoma (OR=1.87; 95% CI=1.32–2.65). Moreover, the genotypic frequency of rs361525 was significantly different between cervical cancer stage I and stage II (P=0.003). Conclusion: The rs1800629 and rs361525 in the TNF-α promoter are associated with susceptibility to CC in the Chinese Han population.