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Smoking and Polymorphisms in Xenobiotic Metabolism and DNA Repair Genes are Additive Risk Factors Affecting Bladder Cancer in Northern Tunisia

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Pathology & Oncology Research

Abstract

Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking and genetic polymorphisms on the occurrence of bladder cancer. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). DNA repair is essential to an individual’s ability to respond to damage caused by tobacco carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to this environmental exposure. Polymorphisms in NAT2, GST and DNA repair genes alter the ability of these enzymes to metabolize carcinogens or to repair alterations caused by this process. We have conducted a case-control study to assess the role of smoking, slow NAT2 variants, GSTM1 and GSTT1 null, and XPC, XPD, XPG nucleotide excision-repair (NER) genotypes in bladder cancer development in North Tunisia. Taken alone, each gene unless NAT2 did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotypes, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk to develop bladder cancer (OR = 7.14; 95% CI: 1.30–51.41). However, in tobacco consumers, we have shown that Null GSTM1, Wild GSTT1, Slow NAT2, XPC (CC) and XPG (CC) are genetic risk factors for the disease. When combined together in susceptible individuals compared to protected individuals these risk factors give an elevated OR (OR = 61). So, we have shown a strong cumulative effect of tobacco and different combinations of studied genetic risk factors which lead to a great susceptibility to bladder cancer.

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Authors and Affiliations

  1. Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University of El Tunis Manar I, 2092, Tunis, Tunisia

    Kamel Rouissi, Karim Bougatef, Raja Marrakchi & Amel Ben Ammar Elgaaied

  2. Pasteur Institute of Tunis, Laboratory of Molecular and Cellular Haematology, Tunis, Tunisia, University of Tunis El Manar, Tunis, Tunisia

    Slah Ouerhani

  3. Department of Urology, Charles Nicole Hospital, Tunis, Tunisia

    Bechr Hamrita, Mohamed Cherif, Mohamed Riadh Ben Slama, Mohamed Bouzouita & Mohamed Chebil

Authors
  1. Kamel Rouissi
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  2. Slah Ouerhani
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  3. Bechr Hamrita
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  4. Karim Bougatef
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  7. Mohamed Riadh Ben Slama
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  10. Amel Ben Ammar Elgaaied
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Correspondence to Kamel Rouissi.

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Kamel Rouissi and Slah Querhani contributed equally to this work

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Rouissi, K., Ouerhani, S., Hamrita, B. et al. Smoking and Polymorphisms in Xenobiotic Metabolism and DNA Repair Genes are Additive Risk Factors Affecting Bladder Cancer in Northern Tunisia. Pathol. Oncol. Res. 17, 879–886 (2011). https://doi.org/10.1007/s12253-011-9398-3

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  • DOI: https://doi.org/10.1007/s12253-011-9398-3

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