POLYMORPHISM OF METABOLIZING GENES AND LUNG-CANCER HISTOLOGY - PREVALENCE OF CYP2E1 IN ADENOCARCINOMA

The relationship between genetic predisposition and development of spe cific cancers has not been adequately elucidated. In this study, the i nvolvement of three polymorphic genes (CYP2E1, GSTM1, and GSTT1) in th e development of different histological types of lung cancer was inves tigated, DNA was extracted from peripheral blood lymphocytes of lung c ancer patients who have been long-term cigarette smokers (n=52). Allel ic variants of CYP2E1 were detected using PCR followed by Pstl restric tion enzyme digest and RFLP analysis, which detects a specific mutatio n causing over-expression of the gene. GSTM1 and GSTT1 genotypes were detected using two separate differential PCR methods, Our results indi cate a 13.5% allele frequency for the CYP2E1 rare Pstl site among the lung cancer patients which represents a 3.4-fold increase over the nor mal controls (OR=3.5, 95% CL=0.65-25.8). A novel observation is that a ll the patients with this polymorphism had adenocarcinomas only, resul ting in a significant association between them (OR=16.17, 95% CL=0.95- 73, P=0.02). The frequency of the null GSTM1 gene was 42.3% among the lung cancer patients with no preferential tendency towards developing squamous cell carcinoma versus adenocarcinoma (OR=1.10, 95% CL=0.3-4.1 4, P=0.5). The GSTT1 gene was absent in 21.1% of the patients with a n on-significant tendency towards developing squamous cell carcinoma (OR =1.23, 95% CL=0.25-6.1, P=0.5). Another important observation is the s ignificant predominance of the three predisposing polymorphic alleles among the adenocarcinoma patients (OR=3.4, 95% CL=0.78-16.1, P=0.05) c ompared with the squamous cell carcinoma patients. The results of this study indicate that the inheritance of several polymorphic metabolizi ng genes, particularly the CYP2E1 gene, contributes not only to the de velopment of lung cancer but also to the development of specific types of cancer. (C) 1997 Elsevier Science Ireland Ltd.