title: Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma.
abstract: OBJECTIVE
  MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of basic cellular functions through posttranscriptional regulations on their target genes. Compelling evidence has shown that miRNAs are involved in cancer initiation and progression. We hypothesized that genetic variations of the miRNA machinery genes could be associated with the risk of renal cell carcinoma.
  
  
  METHODS
  We genotyped 40 single nucleotide polymorphisms (SNP) from 11 miRNA processing genes (DROSHA, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, GEMIN4, HIWI) and 15 miRNA genes in 279 Caucasian patients with renal cell carcinoma and 278 matched controls.
  
  
  RESULTS
  We found that two SNPs in the GEMIN4 gene were significantly associated with altered renal cell carcinoma risks. The variant-containing genotypes of Asn929Asp and Cys1033Arg exhibited significantly reduced risks, with odds ratios (OR) of 0.67 [95% confidence interval (95% CI), 0.47-0.96] and 0.68 (95% CI, 0.47-0.98), respectively. Haplotype analysis showed that a common haplotype of GEMIN4 was associated with a significant reduction in the risk of renal cell carcinoma (OR, 0.66; 95% CI, 0.45-0.97). We also conducted a combined unfavorable genotype analysis including five promising SNPs showing at least a borderline significant risk association. Compared with the low-risk reference group with one unfavorable genotype, the median-risk and high-risk groups exhibited a 1.55-fold (95% CI, 0.96-2.50) and a 2.49-fold (95% CI, 1.58-3.91) increased risk of renal cell carcinoma, respectively (P for trend < 0.001).
  
  
  CONCLUSIONS
  Our results suggested that genetic polymorphisms of the miRNA-machinery genes may affect renal cell carcinoma susceptibility individually and jointly.
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D035683:MicroRNAs