367 Prognosis of occupational bladder cancer and polymorphic xenobiotic metabolising enzymes

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Abstract

Introduction

In recent years, approximately 150 bladder cancer patients per year were acknowledged as an occupational disease in Germany. The question rises whether in genome-wide association studies described bladder risk factors may modulate the prognosis of occupational bladder cancer.

Methods

One hundred and thirty-six cancer patients surveyed for an occupational disease of the bladder were investigated for the course of the disease. EDTA blood samples were drawn. Patients were genotyped for the following polymorphisms: N-acetyltransferase 2 (NAT2, substrate: aromatic amines), glutathione S-transferase M1 (GSTM1, substrate: reactive metabolites of PAH), glutathione S-transferase T1 (GSTT1, substrate: small molecules with 1 or 2 carbon atoms), UDP-glucuronyltransferase 1A2 rs11892031 (UGT1A2, substrate: aromatic amines), rs9642880 (close to c-Myc gene) and rs710521 (close to TP63). Frequencies of recurrences were analysed by means of chi-square test, relapse-free times were analysed by unadjusted Cox regression. The combined effect of the polymorphisms was analysed by means of the weighted polygenic risk score (PRS).

Results

In 38% of the patients a recurrence was reported (median 1.54 years). All investigated polymorphisms except for rs710521 showed a tendency to more frequent recurrences and shorter recurrence-free times, in particular NAT2 (slow vs fast: hazard ratio HR 1.75, 95% CI: 0.98 to 3.12, p=0.0582), GSTM1 (positive versus negative: HR 1.77, 95% CI: 0.70 to 4.48, p=0.2222) and GSTM1 (negative vs positive, HR 1.37, 95% CI: 0.76 to 2, 45, p=0.2972). The PRS was significantly associated with shorter recurrence-free times (PRS >median vs PRS ≤median score: 18 vs 26 months, HR=1.93, 95% CI: 1.06 to 3.53; p=0.0327), the risk of recurrence was also higher (47% vs 31%, OR=1.94, 95% CI: 0.93 to 4.06, p=0.0757).

Conclusion

Polymorphic xenobiotic metabolising enzymes may modulate the prognosis of occupational bladder cancer.

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