Association of CYP2C19*2/3 gene polymorphism with lung cancer in Moroccan population

Background: As it is the case for all kinds of cancer; lung cancer is a multifactorial disease. The interaction between both Exposures to different carcinogens and individual genetic backgrounds modulate the disease risk. Cytochrome P450 family is one of the main enzymes involved in the metabolism of these carcinogens. Therefore, polymorphisms of genes encoding for the cyp450 enzymes can be responsible for the inter-individual differences in lung cancer susceptibility. In this study, we chose to focus on the Cyp2c19, as one of the crucial cyp450 enzymes associated with metabolism of a number of drugs and xenobiotics and its association with the lung cancer risk. Methods: Peripheral blood from a total of 115 Moroccan patients diagnosed with lung cancer and 105 healthy subjects was collected. The genotyping of CYP2C19*2 and CYP2C19*3 polymorphisms was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technic. Results: We found that the frequency of both CYP2C19*2 (GA+AA) genotype and CYP2C19*A allele were significantly more frequent in lung cancer patients than that in control subjects (24.3% vs 13.3%; p = 0.04 and 14.35% vs 7.15%; p = 0.01 respectively). We also found that the CYP2C19*3 A allele was only found in lung cancer patient with a frequency of 10% (p = 0.007). Consequently, the frequency of the CYP2C19*3 (GA + AA) genotype was also significantly more prevalent in lung cancer patients than that in controls (20% vs 0.00%; p = 0.005). We also found that smoking is associated to a higher lung cancer risk in participants carrying CYP2C19*3 or CYP2C19*2 GG genotypes (p < 0.0001, OR = 26.42, 95%CI = 12.38-56.36) and (p < 0.0001, OR = 24,44, 95%CI = 11,13-53,65). While the binary logistic regression analysis demonstrates that interaction of CYP2C19*2 with smoking has no effect on the lung cancer risk, unlike the CYP2C19*3 which coexisted with smoking increases lung cancer risk even more. Conclusion: These findings indicate that the CYP2C19*2 and CYP2C19*3 polymorphisms are significantly associated with lung cancer in Moroccan population. In addition, that the coexistence of CYP2C19*3 with smoking increased lung cancer risk even more.