title: Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer.
abstract: MicroRNAs (miRNA) are small noncoding RNA molecules involved in a diversity of cellular functions. Although it has been reported that global suppression of the miRNA biogenesis pathway leads to enhanced tumorigenesis, the effect of common genetic variants of miRNA-related genes on cancer predisposition is unclear. To better understand this effect, we genotyped 41 single-nucleotide polymorphisms (SNP) from 24 miRNA-related genes in a case-control study conducted in 746 Caucasian patients with bladder cancer and 746 matched controls. The homozygous variant genotype of a nonsynonymous SNP in the GEMIN3 gene (rs197414) was associated with a significantly increased bladder cancer risk [odds ratios (OR), 2.40; 95% confidence interval (95% CI), 1.04-5.56]. Several additional miRNA-related SNPs were also identified that showed a borderline significant association with bladder cancer risk. Haplotype analysis indicated that a common haplotype of the GEMIN4 gene was associated with a significantly increased bladder cancer risk with an OR of 1.25 (95% CI, 1.01-1.54). To assess the aggregate effects of the promising SNPs, we performed a combined unfavorable genotype analysis that included all SNPs showing at least a borderline statistical significance. We found that, compared with the low-risk reference group with less than two unfavorable genotypes, the medium-risk group with two unfavorable genotypes exhibited a 1.29-fold (0.92-1.81) increased risk whereas the high-risk group with more than two unfavorable genotypes exhibited a 1.92-fold (1.36-2.71) increased risk (P(trend) < 0.0001). Overall, this is the first epidemiologic study showing that miRNA-related genetic variants may affect bladder cancer risk individually and jointly.
authors.affiliation: Department of Epidemiology and Urology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D035683:MicroRNAs