Abstract
Introduction: Additional or better markers are needed to guide the clinical monitoring of patients with non-muscle-invasive bladder cancer (NMIBC). Aim: To investigate the influence of occupational exposures and genetic polymorphisms on recurrence and progression of NMIBC. Methods: The study includes 160 NMIBC patients. We collected on questionnaire information on demographic variables, lifetime smoking history, lifetime history of occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons. Genetic polymorphism (glutathione S-transferase M1; T1; P1 (GSTM1; GSTT1; GSTP1); N-acetyltransferase 1; 2 (NAT1; NAT2); cytochrome P450 1B1 (CYP1B1); sulfotransferase 1A1 (SULT1A1); myeloperoxidase (MPO); catechol-O-methyltransferase (COMT); manganese superoxide dismutase (MnSOD); NAD(P)H:quinone oxidoreductase (NQO1); X-ray repair cross-complementing group 1; 3 (XRCC1; XRCC3) and xeroderma pigmentosum complementation group (XPD)) was assessed in peripheral blood lymphocytes. DNA adducts were evaluated by 32P-postlabeling. Predictors of recurrence (histological confirmation of a newly found bladder tumor) and progression (transition of tumor from low-grade to high-grade and/or increase in TNM stage) were identified by multivariate Cox proportional hazard regression with stepwise backward selection of independent variables. Hazard ratios (HR) with 95% confidence interval (95%CI) and two-tail probability of error (p-value) were estimated. Results: The risk of BC progression decreased with the homozygous genotype “ValVal” of both COMT and MnSOD (HR = 0.195; 95%CI = 0.060 to 0.623; p = 0.006). The results on BC recurrence were of borderline significance. No occupational exposure influenced recurrence or progression. Conclusion: Our results are supported by experimental evidence of a plausible mechanism between cause (ValVal genotype of both MnSOD and COMT) and effect (decreased progression of tumor in NMIBC patients). The genetic polymorphisms associated with better prognosis may be used in clinic to guide selection of treatment for patients initially diagnosed with NMIBC. However, external validation studies are required.
Highlights
Additional or better markers are needed to guide the clinical monitoring of patients with non-muscle-invasive bladder cancer (NMIBC)
The standard conservative therapy—transurethral resection (TUR) of the bladder tumor combined with intravesical instillations with Bacillus Calmette-Guérin and/or intravesical chemotherapy (BCG)—can hinder recurrence, but the results in view to progression are inconsistent [6,7,8]
The aim of the present study is to investigate the extent to which the occupational exposures and genetic polymorphisms influence the recurrence and progression of the tumor in a group of NMIBC
Summary
Additional or better markers are needed to guide the clinical monitoring of patients with non-muscle-invasive bladder cancer (NMIBC). Aim: To investigate the influence of occupational exposures and genetic polymorphisms on recurrence and progression of NMIBC. 75% of incident cases of bladder cancer (BC) present as non-muscle-invasive BC (NMIBC) and 25% as muscle-invasive BC (MIBC) [1]. Recurrence of NMIBC has been found as rapidly as in a few weeks after treatment/surgery [2]. The relapsing nature of NMIBC requires frequent clinical checks and repeated treatment [3,4]. The standard conservative therapy—transurethral resection (TUR) of the bladder tumor combined with intravesical instillations with Bacillus Calmette-Guérin and/or intravesical chemotherapy (BCG)—can hinder recurrence, but the results in view to progression are inconsistent [6,7,8]
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