Role of CYP1A1 MspI polymorphism in CYP1A1 gene with susceptibility to lung cancer in Iranian patients

Abstract

• BACKGROUND: Lung cancer has remained the most prevalent malignancy worldwide. It is the fifth leading cause of cancer death in Iran. Nevertheless, during last few years a gradual permanent increase in its incidence has been reported. Although the crucial role of tobacco smoke in lung cancer initiation has long been established, it is tempting to hypothesize that genetic polymorphisms may contribute to lung cancer predisposition. CYP1A1 gene encodes the main enzyme responsible for metabolic activation of several tobacco carcinogens. CYP1A1 MspI (6235T→C) polymorphism is the most studied variation within the CYP1A1, impacts on the basal levels of metabolism and is believed to be associated with elevated lung cancer risk, mainly in Asian population.
• METHODS: We investigated the frequency of this genetic variation in Iranian lung cancer patients through a cross-sectional study. 65 lung cancer cases and 80 healthy controls were recruited.
• RESULTS: The present findings confirmed the low frequency of the variant CYP1A1*2A allele in the control group. A significant increased risk for lung cancer was observed among those who possessed heterozygous (*1/*2A) genotype (OR = 2.79; 95% CI= 1.01-7.65). Adenocarcinoma was more frequent in non-smoker group (P = 0.00064); however, no significant increased risk obtained for squamous cell carcinoma and small cell carcinoma with respect to smoking. CONCLUSIONS: heterozygous (*1/*2A) genotype may increase the risk of lung cancer.
• KEYWORDS: Cytochrome P450, Lung Cancer, Polycyclic Aromatic Hydrocarbon, RFLP-PCR, Tobacco Smoke, Iran