Polymorphism of metabolizing genes and lung cancer histology: prevalence of CYP2E1 in adenocarcinoma.
The relationship between genetic predisposition and development of specific cancers has not been adequately elucidated. In this study, the involvement of three polymorphic genes (CYP2E1, GSTM1, and GSTT1) in the development of different histological types of lung cancer was investigated. DNA was extracted from peripheral blood lymphocytes of lung cancer patients who have been long-term cigarette smokers (n = 52). Allelic variants of CYP2E1 were detected using PCR followed by PstI restriction enzyme digest and RFLP analysis, which detects a specific mutation causing over-expression of the gene. GSTM1 and GSTT1 genotypes were detected using two separate differential PCR methods. Our results indicate a 13.5% allele frequency for the CYP2E1 rare PstI site among the lung cancer patients which represents a 3.4-fold increase over the normal controls (OR = 3.5, 95% CL = 0.65-25.8). A novel observation is that all the patients with this polymorphism had adenocarcinomas only, resulting 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 = 0.3-4.14, P = 0.5). The GSTT1 gene was absent in 21.1% of the patients with a non-significant tendency towards developing squamous cell carcinoma (OR = 1.23, 95% CL = 0.25-6.1, P = 0.5). Another important observation is the significant predominance of the three predisposing polymorphic alleles among the adenocarcinoma patients (OR = 3.4, 95% CL = 0.78-16.1, P = 0.05) compared with the squamous cell carcinoma patients. The results of this study indicate that the inheritance of several polymorphic metabolizing genes, particularly the CYP2E1 gene, contributes not only to the development of lung cancer but also to the development of specific types of cancer.
El-Zein
R A
RA
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-1110, USA.
Zwischenberger
J B
JB
Abdel-Rahman
S Z
SZ
Sankar
A B
AB
Au
W W
WW
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004198:Disease Susceptibility; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase