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Carcinogenesis Advance Access published online on July 24, 2006
Carcinogenesis, doi:10.1093/carcin/bgl131
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Published by Oxford University Press 2006
Received April 7, 2006
Revised July 10, 2006
Accepted July 11, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1, and UGT1A1 on urine 1-hyrdoxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil

Christian C. Abnet 1 *, Renato B. Fagundes 2, Paul T. Strickland 3, Farin Kamangar 1, Mark J. Roth 1, Philip R. Taylor 4, and Sanford M. Dawsey 1

1 Nutritional Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD, USA
2 Universidade Federal de Santa Maria, Departamento de Clínica Médica, Centro de CIências da Saúde, Campus Universitário de Camobi, Santa Maria, RS, Brazil
3 Department of Environmental Health Sciences, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
4 Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD, USA

* To whom correspondence should be addressed.
Christian C. Abnet, E-mail: abnetc{at}mail.nih.gov


  Abstract

Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) -metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with p-values <0.010. Variants in Ahr (rs4986826), CYP1A1 (rs1799814), and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had p-values of 0.074, 0.040, and 0.025 respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1, and CYP1A2 variants listed above were: 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, mate drinking, cachaça, and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r-squared of 0.21, a model with single genotypes for Ahr, CYP1A1, CYP1A2, and CYP1B1 had an r-squared of 0.10 and a model combining both exposure and genotype information had a total r-squared of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population.

Keywords: 1-Hydroxypyrene glucuronide; CYP1A1; CYP1A2; CYP1B1; Ahr; GST; UGT; polymorphism; SNP.
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