Impacts of Single Nucleotide Polymorphisms in three MicroRNAs (miR-146a, miR-196a2 and miR-499) on Susceptibility to Cervical Cancer among Indian Women.

Cervical cancer is the second major female cancer in India and constitutes one fourth of the world's burden. Human Papilloma Virus (HPV) infection is an essential but insufficient cause for cervical cancer. Genetic variants in MicroRNAs (miRNAs/miRs) play an important role in the susceptibility of various types of cancers. To evaluate the association of Single Nucleotide Polymorphisms (SNPs) in miR-146a (rs2910164), miR-196a2 (rs11614913) and miR-499 (rs3746444), with cervical cancer susceptibility in Indian population. Three hundred samples were genotyped by Polymerase chain reaction (PCR)- Restriction fragment length polymorphism (RFLP). Both patients and controls were also screened for the presence of HPV DNA. In this case-control study 125 (83.3%) cervical cancer cases were found to be infected with HPV DNA. The frequency of miR-146a C allele was higher in controls than in cases [OR(95%CI)=0.81(0.57-1.14), p-value=0.258]. miR-196a2 T allele was found to be associated with the decreased risk of cervical cancer [OR(95%CI)=0.36(0.26-0.50), p-value<0.0001]. ~1.22-fold increased risk has been observed in individuals carrying miR-499 TT genotypes [OR(95%CI)=1.22(0.63-2.36), p-value=0.617]. Interaction studies for miR-196a2/miR-499 loci showed that women carrying TT/CC and TT/CT genotypes were less likely to develop cervical cancer than CC/CC combination [p<0.05]. Likewise, miR-146a/miR-196a2 genotypic combinations (CC/TT, CG/TT, GG/TT) followed the similar trend [p<0.05], exhibited the protective effect against cervical cancer with reference to CC/CC group. Combined genotypes of miR-146a/miR-499 [CC/CT, CG/CC, CG/CT, CG/TT, GG/CC, GG/CT, GG/TT] demonstrated a non-significant trend towards higher cervical cancer risk [OR>1.00, p>0.05]. Polymorphisms in miR-146a, miR-196a2 and miR-499 have the prospective to emerge as biomarkers for cervical cancer.