title: Comparison of occupational exposure assessment methods in a case-control study of lead, genetic susceptibility and risk of adult brain tumours.
abstract: OBJECTIVE
  There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix (JEM)) would produce similar results to a previous analysis that found evidence of effect modification of the association between expert-assessed lead exposure and risk of brain tumours by a single nucleotide polymorphism in the ALAD gene (rs1800435).
  
  
  METHODS
  We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumour risk and lead exposure and effect modification by genotype. We evaluated Cohen's κ, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics.
  
  
  RESULTS
  Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert- but not JEM-derived lead exposure estimates. κ Values indicated only modest agreement (<0.5) for the exposure metrics, with the JEM indicating high specificity (∼0.9) but poor sensitivity (∼0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history.
  
  
  CONCLUSIONS
  These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. pbhatti@fhcrc.org
authors.forename: Parveen
authors.initials: P
authors.lastname: Bhatti
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Stewart
authors.forename: Martha S
authors.initials: MS
authors.lastname: Linet
authors.forename: Aaron
authors.initials: A
authors.lastname: Blair
authors.forename: Peter D
authors.initials: PD
authors.lastname: Inskip
authors.forename: Preetha
authors.initials: P
authors.lastname: Rajaraman
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000235:genetics; D004812:Epidemiologic Methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008579:Meningioma / Q000139:chemically induced / Q000235:genetics; D009784:Occupational Diseases / Q000139:chemically induced* / Q000235:genetics; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D020641:Polymorphism, Single Nucleotide; D000623:Porphobilinogen Synthase / Q000235:genetics*
chemical_list: D007854:Lead; D000623:Porphobilinogen Synthase
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