Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer

Abstract

Background: CYP1A1 is one of the commonest genes which had been widely investigated to find the risk of various malignancies in different ethnic groups. The polymorphism in these genes with a combination of environmental exposure has been hypothesized to confer a differential risk of cancer for individuals carrying these genetic variants. Based on this model, individuals with higher CYP1A1 activity would be at increased risk of cancer when exposed to high levels of smoke components. The proposed mechanism involves cytochrome P450 1A1 (CYP1A1), a gene that is inducible by xenobiotics to produce genetic susceptibility for malignancies. Patients and procedures: We performed a case–control study in 205 cases with histopathologically confirmed squamous cell carcinoma of head and neck and reported habits of bidi or cigarettes smoking and 245 similar controls to investigate the role of CYP1A1 polymorphisms in the risk of head and neck cancers especially among smokers of Hyderabad Indian population. Venous blood samples (5 ml) were collected from patients and control groups; genomic DNA was extracted and used for polymerase chain reaction (PCR) to determine the genotypes. RFLP assays were designed to detect each of the variant CYP1A1 alleles. Results and discussion: CYP1A1m1/m1 genotype (OR = 8.12, 95% CI: 3.27–21.30) and CYP1A1w1/m1 showed elevated risk when compared with CYP1A1w1/w1. Similarly CYP1A1w2/m2 (OR = 1.58, 95% CI: 0.94–2.67) and CYP1A1m2/m2 (OR = 6.31, 95% CI: 2.74–18.69) genotypes also showed elevated risk when compared with CYP1A1w2/w2 genotype. This data demonstrated that smoking was a risk factor for head and neck cancers. The m2 mutations were in close linkage disequilibrium with the m1 mutations; 53% m1 mutants had the mutation in the m2 site. Conclusion: Those individuals carrying at least one CYP1A1 m1 or m2 variant allele were at a 2-fold elevated risk for head and neck cancer. Our data clearly demonstrates that CYP1A1 is an important determinant in susceptibility to tobacco-induced head and neck carcinogens and there is an association between genetic polymorphism in the CYP1A1 locus and elevated risk of the type of smoking among Indians. This appears to be a new and important prognostic and diagnostic marker for determining the risk of head and neck cancers genetically.