CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals

P. V. Nerurkar, L. Okinaka, C. Aoki, A. Seifried, A. Lum-Jones, L. R. Wilkens, L. Le Marchand

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1119-1122
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume9
Issue number10
StatePublished - 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Nerurkar, P. V., Okinaka, L., Aoki, C., Seifried, A., Lum-Jones, A., Wilkens, L. R., & Le Marchand, L. (2000). CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals. Cancer Epidemiology Biomarkers and Prevention, 9(10), 1119-1122.