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

Bladder Cancer

BJU Int. 2020 Sep 25. doi: 10.1111/bju.15254. Online ahead of print.


PURPOSE: To identify single nucleotide polymorphisms (SNPs) associated with patterns of aggressiveness of non-muscle invasive bladder cancer (NMIBC).

MATERIALS 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 analyzing the data of a genome-wide association study (GWAS) on 165 patients with bladder cancer. The second step aimed to validate the SNPs previously identified, by genotyping the germline DNA of 311 patients with NMIBC.

RESULTS: Overall, the median age was 66 years [IQR 58-75] and the rate of patients with aggressive NMIBC was comparable between both groups (46% vs. 46%, P=1). GWAS data analysis identified 4 SNPs associated with an aggressive NMIBC (rs12615669, rs4976845, rs2989734, and rs2802288). In the validation cohort, the genotype CC of rs12615669 as well as an age greater than 70 years at the time of diagnosis was 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 for 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.