Absence of association between TLR4 Thr399Ile polymorphism and cervical cancer susceptibility

Abstract

BackgroundToll-like receptors (TLRs) play a key role in pathogen detection and initiating inflammatory response. Several lines of evidence have suggested chronic inflammation as one of the major factors linked to carcinogenesis. Single nucleotide polymorphisms (SNPs) in TLR genes including TLR4 have been shown to be associated with cancer susceptibility, although reports have been conflicting. AimThe present case-control study was designed to ascertain the association of TLR4 C1196T/ Thr399Ile polymorphism with cervical cancer risk among Indian women. Patients and methodsThe study comprised of tumor biopsies from 110 histopathologically diagnosed cervical cancer cases and cervical smears from 141 disease free healthy controls. DNA was obtained using standard proteinase-K digestion and phenol-chloroform extraction method. Genotyping of samples was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. ResultsThe results showed presence of single genotype CC (Thr/Thr) and complete absence of T allele across all the sample types thereby showing genotypic frequency of 1.0, 0.0 and 0.0 for CC, CT and TT respectively in the study population. Patients aged >45 years showed association with late stages of cervical cancer. ConclusionComplete absence of T allele in our study subjects demonstrate no involvement of TLR4 Thr399Ile polymorphism in cervical cancer susceptibility. However, an association between increased age and late clinical staging was observed. A comprehensive analysis on a larger sample size covering diverse ethnic populations of India is warranted to comprehend the role of TLR4 Thr399Ile polymorphism.