212 SINGLE NUCLEOTIDE POLYMORPHISMS OF MICRORNA MACHINERY GENES MODIFY THE RISK OF RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2010212 SINGLE NUCLEOTIDE POLYMORPHISMS OF MICRORNA MACHINERY GENES MODIFY THE RISK OF RENAL CELL CARCINOMA Yohei Horikawa, Christopher Wood, Hushan Yang, Jian Gu, Tomonori Habuchi, and Xifeng Wu Yohei HorikawaYohei Horikawa Akita, Japan More articles by this author , Christopher WoodChristopher Wood Houston, TX More articles by this author , Hushan YangHushan Yang Houston, TX More articles by this author , Jian GuJian Gu Houston, TX More articles by this author , Tomonori HabuchiTomonori Habuchi Akita, Japan More articles by this author , and Xifeng WuXifeng Wu Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.269AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e83 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yohei Horikawa Akita, Japan More articles by this author Christopher Wood Houston, TX More articles by this author Hushan Yang Houston, TX More articles by this author Jian Gu Houston, TX More articles by this author Tomonori Habuchi Akita, Japan More articles by this author Xifeng Wu Houston, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...