title: A GWAS-identified susceptibility locus on chromosome 11q13.3 and its putative molecular target for prediction of postoperative prognosis of human renal cell carcinoma.
abstract: Genome-wide association studies have been used to identify single nucleotide polymorphisms (SNPs) associated with renal cell carcinoma (RCC) in European individuals. The current study aimed to evaluate the correlation between significant SNPs identified in European individuals and the occurrence and postoperative prognosis of RCC in Chinese individuals. A total of 400 cases and 806 controls were involved in the current study. rs4765623, rs7105934, rs7579899 and rs1867785 were genotyped using qPCR, and the expression of cyclin D1 in renal tissue and RCCs was determined via western blotting and immunohistochemistry. The correlation between the SNPs/cyclin D1 expression and overall survival was evaluated using multivariate Cox regression analyses. Of the four SNPs, only rs7105934 was found to significantly correlate with RCC risk in Chinese individuals. The rs7105934 GA + AA genotype was correlated with a reduced risk of RCC with an odds ratio of 0.64 (95% confidence interval [CI], 0.43-0.96), following adjustment for age. This genotype was found to independently predict an improved postoperative prognosis in the multivariate analysis, with a hazard ratio (HR) of 0.12 (95% CI, 0.02-0.93). Expression of cyclin D1, a putative regulated protein of rs7105934, did not vary in adjacent renal tissue and tumors when compared with that of various rs7105934 genotypes. However, cyclin D1 expression in RCCs inversely correlated with advanced tumor stage, and moderate to high expression of cyclin D1 in RCCs independently predicted improved postoperative prognosis, with an HR of 0.13 (95% CI, 0.02-0.96). Observations of the present study indicate that the rs7105934 A allele is associated with reduced risk and improved postoperative prognosis of RCC; however, this effect is unlikely to be caused by cyclin D1 expression.
authors.affiliation: Department of Epidemiology, Second Military Medical University;
authors.forename: Tong
authors.initials: T
authors.lastname: Su
authors.forename: Yifang
authors.initials: Y
authors.lastname: Han
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Yu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Tan
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Li
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hou
authors.forename: Yan
authors.initials: Y
authors.lastname: DU
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.forename: Liye
authors.initials: L
authors.lastname: Ma
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
keywords: cyclin D1; prognosis; renal cell carcinoma; risk; single nucleotide polymorphism