Role of Tobacco Metabolism in the Causation of Oral Squamous Cell Carcinoma in a High-Incidence Area of South Asia

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 without and 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 chewing and smoking index. After age adjustment, 140 OSCC cases and 90 controls were subjected to genetic analysis. White blood cells were used for DNA isolation while CYP1A1 MspI polymorphism was detected with the PCR-RFLP technique. Three polymorphisms were tested namely wild type, heterozygous variant and homozygous variants. Odds Ratios (ORs) were calculated while the precision of ORs was adjusted by 95% confidence interval (CI). The risk was determined by binary logistic regression model 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 most prevalent tobacco habit. Cheek was the most common site (56%) followed by tongue (21%). The frequencies CYP1A1MspI wild-type, heterozygous and homozygous variants were found to be 18.57%, 62.85% and 18.57% among OSCC cases and 26.53%, 62.24% and 11.22% in controls. The homozygous (m2/m2) variant of CYP1A1MspI conferred an increased risk to OSCC 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 considered in 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 oral cancer and this risk seems to be tobacco modulated. Hence CYP1A1MspI homozygous genotype could be a major determinant of high rates of oral cancer in the indigenous population of Karachi.