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.
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.
['Lenfant|Louis|L|0000-0001-9852-4002', 'Cancel-Tassin|Geraldine|G|0000-0002-9583-6382', 'Gazut|Stéphane|S|', 'Compérat|Eva|E|', 'Rouprêt|Morgan|M|', 'Cussenot|Olivier|O|']
D000367:Age Factors D000368:Aged D000483:Alleles D002882:Chromosomes, Human, Pair 13 D002899:Chromosomes, Human, Pair 9 D018450:Disease Progression D005260:Female D055106:Genome-Wide Association Study D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D009361:Neoplasm Invasiveness D009364:Neoplasm Recurrence, Local D009367:Neoplasm Staging D020641:Polymorphism, Single Nucleotide D001749:Urinary Bladder Neoplasms
genetics progression bladder single nucleotide polymorphism #BladderCancer #blcsm #uroonc neoplasm