Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients.
Polymorphisms in xenobiotic metabolizing enzymes have been implicated in inter-individual and inter-ethnic differences in cancer susceptibilty. Several studies have indicated an association between variant alleles of the human CYP1A1, CYP2E1 and GSTM1 genes and lung cancer. Activity of microsomal epoxide hydrolase (HYL1) has also been associated with lung cancer, and 2 variant alleles causing amino acid substitutions have been described. We have investigated genetic polymorphisms of the CYP1A1, CYP2E1, GSTM1 and HYL1 genes in 76 Chinese lung cancer patients and 122 healthy Chinese subjects. The allele frequency of the CYP1A1*2B allele was 0.21 among lung cancer patients and 0.20 in the reference group, whereas the corresponding values for the CYP1A1*2A allele were 0.34 and 0.36. The CYP2E1*5B and CYP2E1*6 alleles were less frequent among the cancer patients (0.20 and 0.22) compared with healthy subjects (0.25 and 0.26). The frequency distribution of the HYL1*2 allele was 0.49 among lung cancer patients and 0.42 in the reference group, and the corresponding frequencies for the HYL1*3 allele were 0.13 and 0.10. The homozygous GSTM1*0 genotype was found in 64% of lung cancer patients and in 66% of healthy subjects. Among heavy smokers, the frequency was 73%. The differences in the distribution of variant CYP1A1, CYP2E1 and GSTM1 alleles in lung cancer patients and healthy controls were not statistically significant. Our results indicate that the polymorphisms investigated are of minor importance as genetic susceptibility markers for lung cancer in this population. An increased risk for lung cancer in subjects carrying the HYL*3 allele was observed and suggests that polymorphism in this gene might possibly be a susceptibility factor in the Chinese population.
Persson
I
I
Institute of Environmental Medicine, Division of Molecular Toxicology, Karolinska Institutet, Stockholm, Sweden. irene.persson@imm.ki.se
Johansson
I
I
Lou
Y C
YC
Yue
Q Y
QY
Duan
L S
LS
Bertilsson
L
L
Ingelman-Sundberg
M
M
D000328:Adult; D000368:Aged; D000483:Alleles; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015262:Xenobiotics / Q000378:metabolism*
D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases