Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk
| Autor: | Umberto Gelatti, Agnès Hautefeuille, Rayjean J. Hung, Paul Brennan, Donatella Placidi, Stefano Porru, Christian Malaveille, Paolo Boffetta, Angela Carta |
|---|---|
| Přispěvatelé: | Hung, R.J., Boffetta, P., Brennan, P., Malaveille, C., Gelatti, U., Placidi, D., Carta, A., Hautefeuille, A., Porru, S. |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cancer Research Manganese Superoxide Dismutase Catechol O-Methyltransferase medicine.disease_cause Tobacco smoke Glutathione Peroxidase GPX1 NAD(P)H Dehydrogenase (Quinone) Humans Medicine Genetic polymorphism environmental exposures bladder cancer Carcinogen Aged Peroxidase Aged 80 and over Cocarcinogenesis Polymorphism Genetic Catechol-O-methyl transferase Bladder cancer biology Superoxide Dismutase business.industry Glutathione Peroxidase GPX1 Manganese Superoxide Dismutase Catalase Environmental Exposure General Medicine Environmental exposure Middle Aged Catalase medicine.disease Urinary Bladder Neoplasms Biochemistry Myeloperoxidase biology.protein Cancer research business Carcinogenesis Oxidative stress |
| Zdroj: | Carcinogenesis. 25:973-978 |
| ISSN: | 1460-2180 |
| DOI: | 10.1093/carcin/bgh080 |
| Popis: | Tobacco smoking and occupational exposure are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines, which lead to oxidative stress and DNA damage. Several enzymes, which play key roles in oxidative stress are polymorphic in humans. Myeloperoxidase (MPO) produces a strong oxidant for microbicidal activity, and activates carcinogens in tobacco smoke. Catechol-O-methyltransferase (COMT) catalyzes the methylation of endo- and xenobiotics and prevents redox cycling. NAD(P)H:quinone oxidoreductase (NQO1) catalyzes the two-electron reduction of quinoid compounds, which also protects cells from redox cycling. Manganese superoxide dismutase (MnSOD) protects cells from free radical injury. To test the hypothesis that the risk of bladder cancer can be influenced by polymorphisms in the genes that modulate oxidative stress, in particular by interacting with environmental carcinogens, we conducted a hospital-based case-control study among men in Brescia, Northern Italy. We recruited and interviewed 201 incident cases and 214 controls from 1997 to 2000. Occupational exposures to PAHs and aromatic amines were coded blindly by occupational physicians. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk and the effect of modifications of smoking and occupational exposures were evaluated. MPO G-463A homozygous variant was associated with a reduced risk of bladder cancer with an OR of 0.31 (95% CI = 0.12-0.80). MnSOD Val/Val genotype increased the risk of bladder cancer with OR of 1.91 (95% CI = 1.20-3.04), and there was a combined effect with smoking (OR = 7.20, 95% CI = 3.23-16.1) and PAH (OR = 3.02,95% CI = 1.35-6.74). We did not observe an effect of COMT Val108Met polymorphism. These findings suggest that individual susceptibility of bladder cancer may be modulated by MPO and MnSOD polymorphisms, and that the combination of genetic factors involved in oxidative stress response with environmental carcinogens may play an important role in bladder carcinogenesis. © Oxford University Press 2004; all rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|