Journal
BJU INTERNATIONAL
Volume 127, Issue 3, Pages 375-383Publisher
WILEY
DOI: 10.1111/bju.15254
Keywords
single nucleotide polymorphism; bladder; neoplasm; genetics; progression; #BladderCancer; #blcsm; #uroonc
Categories
Funding
- `Association Francaise d'Urologie'
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This two-phase study identified three SNPs (rs12615669, rs4976845, and rs2989734) associated with aggressive NMIBC and one SNP (rs4976845) associated with a higher risk of progression.
Objective To identify single nucleotide polymorphisms (SNPs) associated with patterns of aggressiveness of non-muscle-invasive bladder cancer (NMIBC). Patients and Methods From January 2011 to December 2018, 476 patients with NMIBC were prospectively included. The first step aimed to identify SNPs associated with aggressiveness patterns (e.g. >= pT1or high-grade/Grade 3 or presence of carcinomain situ) by analysing the data of a genome-wide association study (GWAS) on 165 patients with BC. The second step aimed to validate the SNPs previously identified, by genotyping the germline DNA of 311 patients with NMIBC. Results Overall, the median (interquartile range) age was 66 (58-75) years and the rate of patients with aggressive NMIBC was comparable between both groups (46% vs 46%,P = 1). GWAS data analysis identified four SNPs associated with an aggressive NMIBC (rs12615669, rs4976845, rs2989734, and rs2802288). In the validation cohort, the genotype CC of rs12615669, as well as age >70 years at the time of diagnosis were associated with aggressive NMIBC (P = 0.008 andP < 0.001, respectively). Genotyping of the entire cohort showed an association between aggressive NMIBC and the T allele of rs12615669 (P = 0.0007), the A allele of rs4976845 (P = 0.012), and the A allele of rs2989734 (P = 0.007). A significant association was also found for the entire cohort between the risk of progression and the A allele of rs4976845 (P = 0.04). Conclusion This two-phase study identified three SNPs (rs12615669, rs4976845, and rs2989734) associated with aggressive NMIBC and one SNP (rs4976845) associated with a higher risk of progression.
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