Association of toll-like receptor gene polymorphisms and its interaction with HPV infection in determining the susceptibility of cervical cancer in Chinese Han population.

Abstract

The aim of the study is to investigate the association of several single-nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and additional gene-gene and gene-human papillomavirus (HPV) infection interaction with cervical cancer risk. A total of 1262 participants are selected, including 420 cervical cancer patients and 842 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among five SNPs within TLR gene and HPV infection. Logistic regression was performed to calculate the ORs (95 %CI) for association of five SNPs within TLR gene and additional gene-HPV infection interaction with cervical cancer risk. Cervical cancer risk was significantly higher in carriers of the T allele of rs3775290 within TLR2 gene, the G allele of rs7873784 within TLR4 gene, and the A allele of rs352140 within TLR9 gene than those with wild genotype; adjusted ORs (95 %CI) were 1.78 (1.20-2.24), 1.65 (1.23-2.12), and 1.70 (1.16-2.31). However, we did not find any significant association of rs4986791 and rs11536889 with cervical cancer risk. GMDR analysis suggested a significant two-locus model (p = 0.0107) involving rs352140 and HPV infection. Subjects with HPV infection and rs352140-GA + AA genotype within TLR9 gene have the highest cervical cancer risk, compared to no HPV infection participants with rs352140-GG genotype, OR (95 %CI) = 3.22 (1.68-4.81). Pairwise LD analysis did not find any significant haplotype combination associated with cervical cancer risk. The minor alleles of TLR2-rs3775290, TLR4-rs7873784, and TLR9-rs352140, and interaction between rs352140 and HPV infection were all associated with increased cervical cancer risk.