Genetic Variants in miRNAs Predict Bladder Cancer Risk and Recurrence

Abstract

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 located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that 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 ¼ 0.80, 95% confidence interval (CI) ¼ 0.71-0.90, P ¼ 2.92 Â 10 À4]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P ¼ 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated 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 ¼ 0.010). Taken together, our findings show 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 Res; 72(23); 6173-82. Ó2012 AACR.

TRAF6 expression is associated with poorer prognosis and high recurrence in urothelial bladder cancer

“…However, in a large screen of effective genetic variants in microRNAs (miRNAs) in bladder cancer, TRAF6 was hypothesized as an effector molecule of miR-146a. miR-146a has an notable role in predicting the risk and recurrence of bladder cancer (30). This supported the results in the present study, which indicated that TRAF6 expression may be a prognostic factor in urothelial bladder cancer.…”

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

“…Most of the samples included in this study had been enrolled in previous association studies (17)(18)(19)(20). All of the subjects were unrelated ethnic Han Chinese.…”

“…Grading and staging were conducted in accordance with the 2004 WHO/ ISUP classification of bladder cancer. For additional follow-up, we collected 226 patients with non-muscle invasive bladder cancer from the Huai-An Hospital (Nanjing, China) starting in May 2005, as described in our previous study (17). Every 3 months, follow-ups were conducted by telephone.…”

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

“…The authors proposed that the SNP could be correlated with the transition from normal to neoplastic thyroid tissue (23). It is worth mentioning that rs2910164 has been later shown to predispose to hepatocellular carcinoma in males (31), prostate cancer (32), bladder cancer (33), and colorectal cancer (34). Rs2910164 is also proposed to contribute to the pathogenesis of breast and ovarian cancer, as the target genes of miR-146a include BRCA1 and BRCA2.…”