Pathomorphological Manifestations and the Course of the Cervical Cancer Disease Determined by Variations in the TLR4 Gene.

Abstract

Cervical cancer (CC) is often associated with human papillomavirus (HPV). Chronic inflammation has been described as one of the triggers of cancer. The immune system fights diseases, including cancer. The genetic polymorphism of pathogen recognition receptors potentially influences the infectious process, development, and disease progression. Many candidate genes SNPs have been contradictory demonstrated to be associated with cervical cancer by association studies, GWAS. TLR4 gene activation can promote antitumor immunity. It can also result in immunosuppression and tumor growth. Our study aimed to investigate eight selected polymorphisms of the TLR4 gene (rs10759932, rs1927906, rs11536898, rs11536865, rs10983755, rs4986790, rs4986791, rs11536897) and to determine the impact of polymorphisms in genotypes and alleles on the pathomorphological characteristics and progression in a group of 172 cervical cancer subjects with stage I-IV. Genotyping was performed by RT-PCR assay. We detected that the CA genotype and A allele of rs11536898 were significantly more frequent in patients with metastases (p = 0.026; p = 0.008). The multivariate logistic regression analysis confirmed this link to be significant. The effect of rs10759932 and rs11536898 on progression-free survival (PFS) and overall survival (OS) has been identified as important. In univariate and multivariate Cox analyses, AA genotype of rs11536898 was a negative prognostic factor for PFS (p = 0.024; p = 0.057, respectively) and OS (p = 0.008; p = 0.042, respectively). Rs11536898 C allele predisposed for longer PFS (univariate and multivariate: p = 0.025; p = 0.048, respectively) and for better OS (univariate and multivariate: p = 0.010; p = 0.043). The worse prognostic factor of rs10759932 in a univariate and multivariate Cox analysis for survival was CC genotype: shorter PFS (p = 0.032) and increased risk of death (p = 0.048; p = 0.015, respectively). The T allele of rs10759932 increased longer PFS (univariate and multivariate: p = 0.048; p = 0.019, respectively) and longer OS (univariate and multivariate: p = 0.037; p = 0.009, respectively). Our study suggests that SNPs rs10759932 and rs11536898 may have the potential to be markers contributing to the assessment of the cervical cancer prognosis. Further studies, preferably with larger groups of different ethnic backgrounds, are needed to confirm the results of the current study.