Carcinogenesis, Vol 18, 967-973, Copyright © 1997 by Oxford University Press
X Wu, H Shi, H Jiang, B Kemp, WK Hong, GL Delclos and MR Spitz
Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of
carcinogenic N-nitrosoamines. We therefore assessed the genotype
frequencies of PstI or RsaI CYP2E1 restriction fragment length
polymorphisms and another susceptibility marker, mutagen sensitivity, in
137 lung cancer cases (92 African American and 45 Mexican American) and 206
controls (114 African American and 92 Mexican American) identified in a
molecular epidemiological study of lung cancer. The CYP2E1 c1/c1 genotype
was found in 86.7% of Mexican American cases, 70.6% of Mexican American
controls, 89.1% of African American cases and 86.8% of African American
controls. By multivariate analysis, this genotype was found to be
associated with a 14.0-fold increased risk of lung cancer in Mexican
Americans but not in African Americans; a 9.9- fold increased risk of lung
cancer in Mexican American former smokers, but not in non-smokers or
current smokers; a 15-fold increased risk of lung cancer in Mexican
American males, but not in females. Patients with the susceptible genotype
appeared to have developed cancer at an earlier age and with lower
cigarette pack-year of exposure than did patients with the c1/c2 or c2/c2
genotypes. Stratified analysis suggested a greater than multiplicative
interaction between cigarette smoking and CYP2E1 c1/c1 genotype, although
not statistically significant. The odds ratios (ORs) for the CYP2E1 c1/c1
genotype, cigarette smoking and both risk factors combined were 1.3, 6.7
and 16.3, respectively. The association between CYP2E1 c1/c1 genotype and
pack-years of smoking followed the same pattern. The interaction between
mutagen sensitivity and CYP2E1 c1/c1 genotype was especially strong in
former smokers (the ORs for the CYP2E1 c1/c1 genotype, mutagen sensitivity
and both risk factors combined were 3.9, 5.4 and 23.0, respectively).
Therefore, the data suggest that individuals who lack a c2 allele might be
at higher risk for developing lung cancer.
ARTICLES
Associations between cytochrome P4502E1 genotype, mutagen sensitivity, cigarette smoking and susceptibility to lung cancer
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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