Occupational solvent exposure, genetic variation of DNA repair genes, and the risk of non-Hodgkin's lymphoma

Eur J Cancer Prev. 2012 Nov;21(6):580-4. doi: 10.1097/CEJ.0b013e328351c762.

Abstract

The main objective of this study was to test the hypothesis that genetic variations in DNA repair genes may modify the association between occupational exposure to solvents and the risk of non-Hodgkin's lymphoma (NHL). A population-based case-control study was conducted on Connecticut women including 518 histologically confirmed incident NHL cases and 597 controls. Unconditional logistic regression models were used to estimate the odds ratios and effect modification from the 30 single nucleotide polymorphisms in 16 DNA repair genes of the association between solvent exposure and the risk of NHL overall and subtypes. Single nucleotide polymorphisms in MGMT (rs12917) and NBS1 (rs1805794) significantly modified the association between exposure to chlorinated solvents and the risk of NHL (Pfor interaction=0.0003 and 0.0048, respectively). After stratification by major NHL histological subtypes, MGMT (rs12917) modified the association between chlorinated solvents and the risk of diffuse large B-cell lymphoma (Pfor interaction=0.0027) and follicular lymphoma (Pfor interaction=0.0024). A significant interaction was also observed between occupational exposure to benzene and BRCA2 (rs144848) for NHL overall (Pfor interaction=0.0042). Our study results suggest that genetic variations in DNA repair genes modify the association between occupational exposure to solvents and the risk of NHL.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA2 Protein / genetics
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics
  • Connecticut / epidemiology
  • DNA Modification Methylases / genetics
  • DNA Repair / genetics*
  • DNA Repair Enzymes / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lymphoma, Follicular / epidemiology
  • Lymphoma, Follicular / etiology*
  • Lymphoma, Large B-Cell, Diffuse / epidemiology
  • Lymphoma, Large B-Cell, Diffuse / etiology*
  • Middle Aged
  • Nuclear Proteins / genetics
  • Occupational Exposure / adverse effects*
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Risk Factors
  • Solvents / adverse effects*
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Solvents
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes