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Abstract

Objective: To establish the association between CYP1A1 MspI polymorphism, tobacco-habit and oral cancer.Methodology: 150 Oral squamous cell carcinoma (OSCC) and 108 controls were enrolled, comprising of individuals withoutand with tobacco habits which match in frequency and duration with patients. Study subjects were divided into four groups,namely: exclusive chewers, exclusive smokers, mixed-habit and no habit. Lifetime tobacco exposure was calculated as chewingand smoking index. After age adjustment, 140 OSCC cases and 90 controls were subjected to genetic analysis. White bloodcells were used for DNA isolation while CYP1A1 MspI polymorphism was detected with the PCR-RFLP technique. Threepolymorphisms were tested namely wild type, heterozygous variant and homozygous variants. Odds Ratios (ORs) were calculatedwhile the precision of ORs was adjusted by 95% confidence interval (CI). The risk was determined by binary logistic regressionmodel with CYP1A1 m1/m1 as the reference category.Results: Out of all 258 studied subjects, 60.85% subjects were exclusive tobacco chewers which turned out to be the mostprevalent tobacco habit. Cheek was the most common site (56%) followed by tongue (21%). The frequencies CYP1A1MspIwild-type, heterozygous and homozygous variants were found to be 18.57%, 62.85% and 18.57% among OSCC cases and26.53%, 62.24% and 11.22% in controls. The homozygous (m2/m2) variant of CYP1A1MspI conferred an increased risk toOSCC with an OR of 2.36 (95% CI, 1.0-6.20, p=0.05). OR further increased to 7.2 (95% CI, 1.8-27.5, p=0.003) when consideredin exclusive tobacco chewer’s and 26 (95% CI, 2.2-304.5, p=0.009) in the above median exposure group.Conclusion: Present analysis showed a clear association between CYP1A1MspI polymorphism and the increased risk for oralcancer and this risk seems to be tobacco modulated. Hence CYP1A1MspI homozygous genotype could be a major determinantof high rates of oral cancer in the indigenous population of Karachi.