The rs767649 polymorphism in the promoter of miR-155 contributes to the decreased risk for cervical cancer in a Chinese population.

ABSTRACT

Genetic variants in miRNAs have attracted more and more attention these years because they are capable of altering miRNA function and/or expression, consequently affecting downstream biological pathways and disease risk. The rs767649 polymorphism, locating in the promoter of miR-155, was recently reported to be able to alter transcriptional activity of miR-155 and relate to lung cancer risk. In this study, we aimed to assess the relationship between rs767649 and cervical cancer (CC) risk. We investigated the association of rs767649 with CC risk in a two-stage case-control study with 1157 cases and 1280 controls. Genotyping was determined with TaqMan allelic discrimination method. The results showed that the rs767649 TT genotype was associated with a significantly reduced risk of CC in both test (549 cases and 603 controls), validation (608 cases and 677 controls) and combined sets [adjusted odds ratio (OR)=0.67, 95% confidence interval (CI)=0.51-0.87 for the combined set] compared with the AA/AT genotypes. Moreover, the association was more prominent among patients of age>49years and postmenopausal status (OR=0.56, 95% CI=0.38-0.83, and 0.60, 0.40-0.89, respectively) and patients with clinical stage I and II CC (OR=0.67, 95% CI=0.50-0.91, and 0.60, 0.40-0.92, respectively). Further analyses showed that miR-155 was overexpressed in the CC tissues as compared with normal tissues, suggesting an oncogenic role in CC. Luciferase assay indicated that the transition of A to T allele might lead to miR-155 downregulation at the transcriptional level. In conclusion, rs767649 might be a causal variant for CC susceptibility.