Genetic variants in microRNAs predict bladder cancer risk and recurrence
Menée sur 1 019 patients atteints d'un cancer de la vessie et sur 1 182 témoins, cette étude évalue l'association entre cinq polymorphismes à simple nucléotide de micro-ARNs et le risque de cancer de la vessie et de récidive
MicroRNAs (miRNAs) play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single nucleotide polymorphisms (SNPs) located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1019 bladder cancer cases and 1182 controls (683 cases and 728 controls in the training set, and 336 cases and 454 controls in the test set). We found the miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set (OR = 0.80, 95%CI = 0.71-0.90, P = 2.92×10-4). Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed the miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulates expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings demonstrate that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.
Cancer Research , résumé, 2012