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

Details

• Personal Author:
  Abnet CC ; Dawsey SM ; Fagundes RB ; Kamangar F ; Roth MJ ; Strickland PT ; Taylor, Philip R.
• Description:
  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 aryl hydrocarbon receptor (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, maté drinking, cachaça and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r2 of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r2 of 0.10; and a model combining both exposure and genotype information had a total r2 of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population. [Description provided by NIOSH]
• Subjects:
  Aging Carcinogens Energy Metabolism Genetics Men Occupational Health Pyrenes Safety Women
• Keywords:
  Age-groups Humans Metabolism
• ISSN:
  0143-3334
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  112-117
• Volume:
  28
• Issue:
  1
• NIOSHTIC Number:
  nn:20038275
• Citation:
  Carcinogenesis 2007 Jan; 28(1):112-117
• Contact Point Address:
  Christian C. Abnet, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS/320, MSC 7232, Rockville, MD 20852
• Email:
  abnetc@mail.nih.gov
• Federal Fiscal Year:
  2007
• Performing Organization:
  Johns Hopkins University
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Carcinogenesis
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d772de345b5804520036a1446e587371895fc3977db3fbb7186a816708711d16bb88cb85b99836d8f4ed489e584b1f9c866f057ad9175a48cb09df075d649c60
• Download URL:
  https://stacks.cdc.gov/view/cdc/192037/cdc_192037_DS1.pdf
• File Type:
  [PDF - 107.93 KB ]