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Objective: To detect polymorphisms of CYP1A1, GSTM1 and GSTT1 gene loci among various tobacco habit groups and to relate these with susceptibility of individuals to oral squamous cell carcinoma. Study Design: A cross-sectional case-control study. Place and Duration: Department of Pathology, Ziauddin University, Karachi from 5th January 2012 to 1st January 2017. Methodology: The study comprises of 140 histologically confirmed oral squamous cell carcinoma cases and 98 habit-matched controls. Life-time tobacco-exposures were calculated as tobacco chewing and smoking indices for evaluation between cases and controls. Routine histopathology was followed by molecular analysis by employing Polymerase Chain Reaction (PCR) and PCR-Restriction Fragment Length Polymorphism (RFLP) techniques. Results: The CYP1A1MspI heterozygous variant showed no significant association with oral cancer. The homozygous variant contributed an enhanced risk (OR=2.36, 95% CI, 1.0-6.20). When detected in exclusive chewer’s category, the risk and hence the OR increased to 7.2, 95% CI, 1.8-27.5. The risk conferred was further increased in the above median tobacco intake group, OR=26, 95% CI, 2.2-304.5. For GSTM1 null genotype, no significant association was observed. However, the GSTT1 null polymorphism revealed an overall OR=6.63, 95% CI, 1.49-29.4, independent of presence or absence of tobacco as an environmental insult. Conclusion: Two out of three xenobiotic metabolizing enzyme genes evaluated in this study, namely CYP1A1 MspI and GSTT1, significantly affected oral cancer risk and particular tobacco exposure seems to modify this risk in the former. Keywords: Polymerase chain reaction, Restriction fragment length polymorphism, Habit-matched controls, Tobacco indices, Xenobiotic metabolizing enzyme, Oral squamous cell carcinoma. How to Cite This: Alamgir MM, Mirza T, Jamal Q. Genetic polymorphisms of Xenobiotic Metabolizing Enzymes (XMEs), tobacco habit and susceptibility to oral cancer among citizens of Karachi. Isra Med J. 2021; 13(3): 153-158.

Muhammad Mohiuddin Alamgir, Talat Mirza, Qamar Jamal. (2021) Genetic polymorphisms of Xenobiotic Metabolizing Enzymes (XMEs), tobacco habit and susceptibility to oral cancer among citizens of Karachi., Isra Medical Journal, Volume 13, Issue 03.
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