title: Genetic variations in microRNAs and the risk and survival of renal cell cancer.
abstract: MicroRNAs (miRNAs) are a class of short non-coding, single-stranded RNAs, which perform posttranscriptional regulatory functions as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) genes are currently being identified for contributing to cancer risk, prognosis and survival. We investigated whether genetic variations of miRNAs were associated with the risk and prognosis of renal cell carcinoma (RCC). We genotyped four common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913 and miR-499 rs3746444) to assess their associations with RCC risk in a two-stage case-control study (355 cases and 362 controls in discovery set, meanwhile 647 cases and 660 controls in validation set), as well as RCC survival in 311 patients. We found that the miR-196a2 SNP rs11614913 was associated with RCC susceptibility in recessive model [CC versus TT/TC, adjusted odds ratio = 0.65, 95% confidence interval (CI) = 0.52-0.83] and with survival of RCC in dominant model (TC/CC versus TT, adjusted hazard ratio = 0.40, 95% CI = 0.18-0.89). Meanwhile, the rs11614913 CC genotype was associated with the significantly decreased expression of miR-196a-5p in 26 renal cancer tissues (P = 0.018). Moreover, luciferase reporter assays revealed the potential effect of rs11614913 SNP on the binding of miR-196a-3p to its targets. These results suggested that the miR-196a2 rs11614913 may contribute to the genetic susceptibility and prognosis for RCC, which may act as a biomarker for RCC occurrence and prognosis.
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center and Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Mulong
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Urology, Yizheng Hospital, Drum Tower Hospital Group of Nanjing, 1 Ring South Road, Yizheng 211900, China and.
authors.forename: Desheng
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center and Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center and Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center and Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.affiliation: Department of Urology, Yizheng Hospital, Drum Tower Hospital Group of Nanjing, 1 Ring South Road, Yizheng 211900, China and.
authors.forename: Xuping
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center and Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center and Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China, drzdzhang@gmail.com.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D002291:Carcinoma, Papillary / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: C542543:MIRN196 microRNA, human; D035683:MicroRNAs