Approximately 7% of all
bladder cancer cases in males are associated with occupation. The question arises whether the use of genome-wide association studies was able to identify
bladder cancer risk factors that may modulate occupational
bladder cancer risk and prognosis. One hundred and forty-three
bladder cancer cases with suspected occupational
bladder cancer and 337 controls were genotyped for the following polymorphisms: N-
acetyltransferase 2 (NAT2),
glutathione S-transferase M1 (GSTM1),
glutathione S-transferase T1 (GSTT1),
UDP-
glucuronyltransferase 1A rs11892031 (UGT1A), rs9642880 (close to c-MYC), and rs710521 (close to TP63). The most relevant polymorphisms for occupational
bladder cancer risk were GSTM1 and UGT1A, especially when co-occurring (GSTM1 negative and rs11892031[A/A]: 48% cases vs. 38% controls, OR 1.47, 95% CI 0.99-2.20). The effect was more pronounced in smokers. GSTM1 negative genotype occurred more frequently in
cancer cases exposed to aromatic
amines, carbolineum, and in painters and varnishers. UGT1A (rs11892031[A/A]) was found frequently in cases exposed to carbolineum, crack test spray, PAH, and in painters and varnishers. All investigated polymorphisms except rs710521 (TP63) seemed to exert an impact on recurrence risk. Relapse-free times were shorter for NAT2 slow and ultra-slow, GSTT1 positive and GSTM1 negative cases. Occupational
bladder cancer cases with a number of risk variants displayed significantly shorter relapse-free times compared to cases with few, less relevant risk alleles as evidenced by median difference 8 months. In conclusion, in the present, suspected occupational
bladder cancer cases phase II polymorphisms involved in bladder
carcinogen metabolism modulate
bladder cancer recurrence. Most relevant for
bladder cancer risk were GSTM1 and UGT1A but not NAT2.