Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. Export

@article{citeulike:3740026, abstract = {PURPOSE: 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. EXPERIMENTAL DESIGN: 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.}, author = {Horikawa, Yohei and Wood, Christopher G. and Yang, Hushan and Zhao, Hua and Ye, Yuanqing and Gu, Jian and Lin, Jie and Habuchi, Tomonori and Wu, Xifeng}, citeulike-article-id = {3740026}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-08-1199}, citeulike-linkout-1 = {http://clincancerres.aacrjournals.org/content/14/23/7956.abstract}, citeulike-linkout-2 = {http://clincancerres.aacrjournals.org/content/14/23/7956.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19047128}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19047128}, day = {1}, doi = {10.1158/1078-0432.CCR-08-1199}, issn = {1078-0432}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, keywords = {cancer, carcinoma, cell, microrna, mirna, renal, snp}, month = {December}, number = {23}, pages = {7956--7962}, posted-at = {2009-11-03 19:59:37}, priority = {2}, title = {Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma.}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-08-1199}, volume = {14}, year = {2008} }

TY - JOUR ID - citeulike:3740026 L3 - citeulike-article-id:3740026 N2 - PURPOSE: 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. EXPERIMENTAL DESIGN: 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. IS - 23 JF - Clinical cancer research : an official journal of the American Association for Cancer Research SN - 1078-0432 EP - 7962 TI - Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. VL - 14 SP - 7956 KW - cancer KW - carcinoma KW - cell KW - microrna KW - mirna KW - renal KW - snp AU - Horikawa, Yohei AU - Wood, Christopher AU - Yang, Hushan AU - Zhao, Hua AU - Ye, Yuanqing AU - Gu, Jian AU - Lin, Jie AU - Habuchi, Tomonori AU - Wu, Xifeng PY - 2008/12/01/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-08-1199 ER -