Genetic variability in 13q33 and 9q34 is linked to aggressiveness patterns and a higher risk of progression of non‐muscle‐invasive bladder cancer at the time of diagnosis. (15th October 2020)

• Record Type: Journal Article
• Authors: Lenfant, Louis; Cancel‐Tassin, Geraldine; Gazut, Stéphane; Compérat, Eva; Rouprêt, Morgan; Cussenot, Olivier
• Is Part Of: BJU international. Volume 127:Number 3(2021)
• Page Start: 375
• Page End: 383
• Publication Date: 2020-10-15
• Subjects: single nucleotide polymorphism -- bladder -- neoplasm -- genetics -- progression -- #BladderCancer -- #blcsm -- #uroonc; Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.15254
• Languages: English
• ISSNs: 1464-4096

Abstract

Abstract : 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 carcinoma in 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 and P < 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.