Genetic Score Calculation And Risk Prediction Model Construction Of Bladder Cancer

[Background] Bladder cancer is one of the most common malignancies cancers. Due to the improvement of bladder cancer diagnosis, and the change of life style, The incidence of bladder cancer increased considerably in China in the last decade. In China, the incidence of bladder cancer in 2012 was 6.61/105 and becomes a major public health concern. This cancer not only brought serious pains for bladder cancer cases, but also brought heavy economic burden for families and society. Recently, researchers in Europe and the United States have made significant progress in genetic association studies of bladder cancer and identified more than 13 bladder cancer risk-associated loci in populations of European descent by genome-wide association studies (GWAS). Among these, three of these SNPs were validated in the Chinese population. But it is unclear the combined effect of 3 SNPs in the Chinese population[Method] Three previously established bladder cancer risk-associated SNPs were genotyped by TaqMan probes 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 to predict genetic susceptibility to bladder cancer in Chinese. A risk prediction model for bladder cancer with genetic score, smoking status(yes or no), body mass index(BMI) was developed adjusted by age and gender. The model discriminatory ability and accuracy were evaluated by the area under the curve (AUC), calculated as the area under receiver operating characteristic (ROC) curve and Hosmer-Lemeshow goodness-of-fit test respectively.[Results]1. 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-05.2. Compared to 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=0.0007.3. 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=0.001.4. Based on all male subjects, the risk prediction model of bladder cancer as 0.085 XBMI, both of the model discriminatory ability(AUC=0.61) and accuracy (P-value=0.11>0.05)were significant respectively.[Conclusion]1. A combination of three previously implicated bladder cancer risk-associated SNPs is a significant predictor of genetic susceptibility to bladder cancer in Chinese.2. A risk prediction model for male bladder cancer in Chinese was developed.