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Article type: Research Article
Authors: Singh, Arvind P.c | Pant, Mohan C.a | Ruwali, Munindrac | Shah, Parag P.c | Prasad, Rajendrab | Mathur, Neerajc | Parmar, Devendra*
Affiliations: [a] Developmental Toxicology Division, Department of Radiotherapy, C.S.M. Medical University, Lucknow, India | [b] Developmental Toxicology Division, Department of Tuberculosis and Chest Diseases, C.S.M. Medical University, Lucknow, India | [c] Developmental Toxicology Division, Environmental Epidemiology Division, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), M.G. Marg, Lucknow, India
Correspondence: [*] Address for correspondence: Dr. Devendra Parmar, Developmental Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), P.O. Box 80, M.G. Marg, Lucknow-226 001, U.P, India. Tel.: +91 522 2627586, Ext. 261; Fax: +91 522 2628227, 2621547; E-mail: parmar_devendra@hotmail.com.
Abstract: The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.
Keywords: Lung cancer, risk, CYP1A2, polymorphism, tobacco
DOI: 10.3233/CBM-2011-0224
Journal: Cancer Biomarkers, vol. 8, no. 6, pp. 351-359, 2011
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