title: Genetic score of multiple risk-associated single nucleotide polymorphisms is a marker for genetic susceptibility to bladder cancer.
abstract: Genome-wide association studies have identified 13 single nucleotide polymorphisms (SNPs) that are associated with bladder cancer; three of these SNPs were validated in the Chinese population. This study assessed the performance of these three SNPs, in combination, to predict genetic susceptibility to bladder cancer in Chinese. Three previously established bladder cancer risk-associated SNPs (rs798766 in TACC3, rs9642880 in MYC, and rs2294008 in PSCA) were genotyped in 1,210 bladder cancer patients and 1,008 control subjects in Shanghai, China. A genetic score was calculated for each subject based on these three SNPs. Each of these three SNPs was significantly associated with bladder cancer risk in this independent study population, P < 0.05. The genetic score based on these three SNPs was significantly higher in cases than controls, with a mean of 1.05 and 0.99, respectively, P = 1.03E-05. Compared with subjects with a genetic score <= 1.00, subjects with an elevated genetic score (>1.00) had a significantly increased risk for bladder cancer after adjusting for age, gender, and smoking status, OR = 1.58, 95% Confidence Interval (CI) = 1.21 - 2.06, P = 0.0007. When tested separately for lower (Ta) or higher (Tis, T1-T4) tumor stage, the association was significantly stronger for lower (OR = 2.24, 95% CI = 1.66 - 3.01, P = 1.02E-07) than higher tumor stage (OR = 1.33, 95% CI = 1.00 - 1.78, P = 0.05), P = 0.001. In conclusion, A combination of three previously implicated bladder cancer risk-associated SNPs is a significant predictor of genetic susceptibility to bladder cancer in Chinese.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Haowen
authors.initials: H
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Gu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lin
authors.forename: Guowei
authors.initials: G
authors.lastname: Xia
authors.forename: Zujun
authors.initials: Z
authors.lastname: Fang
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics*
chemical_list: D005819:Genetic Markers