Polymorphisms for vinyl chloride metabolism in French vinyl chloride workers.
Genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) have been shown to influence the degree of genetic damage in Taiwanese workers exposed to the carcinogen - vinyl chloride(VC). Certain French VC workers have been found to express biomarkers of mutant forms of cancer-related proteins (ras-p21 and p53) that have been related to their exposure. ALDH2 and CYP2E1 polymorphisms were investigated in 211 of these workers in an attempt to correlate differences in VC metabolic capacity with differences in the presence of these biomarkers. All of the workers were found to have the normal, wild-type ALDH2 gene, and none of them were found to be homozygous for the variant CYP2E1 allele. Sixteen workers were found to be heterozygous for the variant CYP2E1 allele. After adjusting for age, smoking, drinking and cumulative VC exposure, the odds ratio for the presence of either the mutant ras-p21 or the mutant p53 biomarker in these heterozygous workers was found to be statistically significantly increased in comparison to their homozygous, wild-type counterparts (OR = 5.05; 95% CI = 1.10-23.25). However, as opposed to the case in Taiwanese workers, these polymorphisms are relatively uncommon, and thus differences in ALDH2 and CYP2E1 can account for only a small proportion of the variability in mutagenic response to VC exposure in a Caucasian population.
Li
Yongliang
Y
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Marion
Marie J
MJ
Ho
Renee
R
Cheng
Tsun J
TJ
Coulibaly
Drissa
D
Rosal
Ramon
R
Brandt-Rauf
Paul W
PW
D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000097:blood / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001483:Base Sequence; D019392:Cytochrome P-450 CYP2E1 / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005602:France; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009784:Occupational Diseases / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D011110:Polymorphism, Genetic; D014752:Vinyl Chloride / Q000378:metabolism*
D017931:DNA Primers; D005819:Genetic Markers; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D014752:Vinyl Chloride