Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue.

ABSTRACT

Individual differences in lung cancer susceptibility should be considered for effective lung cancer prevention. We investigated the CYP2E1, ADH3, and GSTP1 genetic polymorphisms that biotransform xenobiotic carcinogens, and variations of their enzyme activity in Caucasian lung tissues (N=28), and found a variant distribution in pulmonary ADH and CYP2E1 activity. The ADH3*1/*1 subjects (N=8) showed significantly higher ADH activity than ADH3*2/*2 (N=3) subjects (P<0.01). On the other hand, we found a 5-fold variation in the pulmonary CYP2E1 activity using a sensitive HLPC/EC based technique. A subject with the CYP2E1-c/t allele showed 2-fold higher CYP2E1 activity than subjects with the c/c allele (N=14). GSTP1 expression comprised 83% of the total pulmonary GSTs. However, neither the GSTP1 polymorphism, nor other lifestyle factors, such as age, gender, smoking status, were found to be associated with pulmonary GST expression. In conclusion, subjects with the ADH3*1 allele showed higher ADH activity and acetaldehyde-DNA adducts in lung than other subjects; thus, the ADH3*1 allele could be considered a risk factor for lung cancer.