TY - JOUR
T1 - CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals
AU - Nerurkar, P. V.
AU - Okinaka, L.
AU - Aoki, C.
AU - Seifried, A.
AU - Lum-Jones, A.
AU - Wilkens, L. R.
AU - Le Marchand, L.
PY - 2000
Y1 - 2000
N2 - The CYP1A1 and glutathione S-transferase enzymes (e.g., GSTM1 and GSTP1) are involved in the activation and conjugation of polycyclic aromatic hydrocarbons (PAHs), respectively, and are controlled by genes that are polymorphic. The CYP1A1*2 allelic variant has been associated with elevated urinary 1-hydroxypyrene (1-OHP), a proposed marker for internal dose of activated PAHs, in coke-oven workers. We investigated whether this association could be observed at low exposure levels, such as those experienced by the general population. We conducted a cross-sectional study among 188 individuals (106 Japanese, 60 Caucasians, and 22 Hawaiians) who were selected as controls in a population-based case-control study and provided lifestyle information, a 12-h urine specimen, and a blood sample. 1-OHP was analyzed by high-performance liquid chromatography after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping. Smokers excreted twice as much 1-OHP (geometric mean, 0.51 nmol/12 h) as nonsmokers (geometric mean, 0.27 nmol/12 h; P = 0.006). Overall and among nonsmokers, 1-OHP urinary levels did not differ by CYP1A1, GSTM1, or GSTP1 genotypes. However, after adjusting for age, ethnicity, and number of cigarettes per day, smokers with at least one CYP1A1*2 variant allele excreted 2.0-fold more 1-OHP than smokers with the wild-type genotype (P = 0.02). Similar results were obtained for the CYP1A1*3 variant allele. The present data add to the growing evidence suggesting that individuals with the (linked) CYP1A1*2 or *3 variant alleles have a greater capacity to activate PAHs from tobacco smoke and occupational exposure and, as a result, are at greater risk for PAH-related cancers, especially certain respiratory cancers.
AB - The CYP1A1 and glutathione S-transferase enzymes (e.g., GSTM1 and GSTP1) are involved in the activation and conjugation of polycyclic aromatic hydrocarbons (PAHs), respectively, and are controlled by genes that are polymorphic. The CYP1A1*2 allelic variant has been associated with elevated urinary 1-hydroxypyrene (1-OHP), a proposed marker for internal dose of activated PAHs, in coke-oven workers. We investigated whether this association could be observed at low exposure levels, such as those experienced by the general population. We conducted a cross-sectional study among 188 individuals (106 Japanese, 60 Caucasians, and 22 Hawaiians) who were selected as controls in a population-based case-control study and provided lifestyle information, a 12-h urine specimen, and a blood sample. 1-OHP was analyzed by high-performance liquid chromatography after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping. Smokers excreted twice as much 1-OHP (geometric mean, 0.51 nmol/12 h) as nonsmokers (geometric mean, 0.27 nmol/12 h; P = 0.006). Overall and among nonsmokers, 1-OHP urinary levels did not differ by CYP1A1, GSTM1, or GSTP1 genotypes. However, after adjusting for age, ethnicity, and number of cigarettes per day, smokers with at least one CYP1A1*2 variant allele excreted 2.0-fold more 1-OHP than smokers with the wild-type genotype (P = 0.02). Similar results were obtained for the CYP1A1*3 variant allele. The present data add to the growing evidence suggesting that individuals with the (linked) CYP1A1*2 or *3 variant alleles have a greater capacity to activate PAHs from tobacco smoke and occupational exposure and, as a result, are at greater risk for PAH-related cancers, especially certain respiratory cancers.
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M3 - Article
C2 - 11045797
AN - SCOPUS:0033785547
VL - 9
SP - 1119
EP - 1122
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 10
ER -