Genetic risk scores based on risk-associated single nucleotide polymorphisms can reveal inherited risk of bladder cancer in Chinese population

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Abstract

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with bladder cancer (BCa) risk in Caucasian and East Asian population. The objective of this study was to validate these SNPs in Chinese population and evaluate whether these SNPs could differentiate the individual inherited risk for BCa. A case-control study including 581 BCa cases and 1561 healthy controls was performed. Germline DNA samples from all individuals were genotyped for eight SNPs. Genetic risk score (GRS) was calculated for each individual based on the odds ratios and risk allele frequencies of five risk-associated SNPs. Among eight SNPs evaluated in this study, rs798766 at 4p16.3 [OR = 1.39 (1.15–1.67), P < .001], rs9642880 [OR = 1.17 (1.06–1.30), P < .001] and rs4813953 at 20p12.2 [OR = 1.09 (1.02–1.17), P = .016] were found associated with BCa risk in Chinese population. A genetic risk score was established based on five SNPs (including the above three SNPs and two other SNPs which have the consistent direction with previous reported genome-wide association study). The mean GRS was significantly higher in BCa cases than controls (1.22 vs. 1.01, P < .001). When subjects were categorized into low- (<0.8), average- (0.8–1.2), and high-risk (>1.2) groups, the likelihoods of BCa were 25.2%, 33.7% and 55.0%, respectively (P-trend < 2.2 × 10-16). In subgroup analyses, no significant difference was observed in mean GRS among BCa patients with different stages or grades. In conclusion, two SNPs derived from East Asian and one SNP from Caucasian were associated with BCa risk in Chinese population. These results provided additional information of genetic risks for BCa in Chinese population. Genetic risk score based on these SNPs can reveal inherited risk of BCa, and may have potential for modifying personalized cancer screening strategy.

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Xu, C., Lin, X., Qian, W., Na, R., Yu, H., Jia, H., … Xu, J. (2020). Genetic risk scores based on risk-associated single nucleotide polymorphisms can reveal inherited risk of bladder cancer in Chinese population. Medicine (United States), 99(19). https://doi.org/10.1097/MD.0000000000019980

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