Association detection between genetic variants in the microRNA binding sites of toll-like receptors signaling pathway genes and bladder cancer susceptibility

摘要

Bladder cancer (BCa) is the second most common urological malignancy, and the incidence of BCa has dramatically increased recently. Various toll-like receptors (TLRs) signaling pathway proteins were proven to be associated with BCa susceptibility. However, the effect of genetic variants in TLRs signaling pathway genes on risk of BCa has not been elucidated clearly. Previous studies mainly focused on the coding region of target genes, while in this study, polymorphisms in the non-coding region, microRNA (miRNA) binding sites were investigated as potential targets. We used bioinformatics approach to screen 100 BCa related TLRs signaling pathway genes. Candidate polymorphisms were select in this region and 8 polymorphisms were confirmed. Rs72552316, located at the 3’UTR of the TLR7 gene, exhibited significant association with risk of BCa, indicating a strong relationship with decreased risk of BCa (P ≤ 0.0001). Furthermore, no association was detected between all the polymorphisms and recurrence-free survival time of overall study population or non-muscle invasive BCa subgroups. In conclusion, rs72552316 in the miRNA binding sites of TLR7 might contribute to BCa susceptibility, and this finding provided new targets for high BCa risk population screening.