title: ras oncogene activation and occupational exposures in acute myeloid leukemia.
abstract: BACKGROUND
  Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures.
  
  
  OBJECTIVE
  This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures.
  
  
  METHODS
  We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS).
  
  
  RESULTS
  Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals (OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects.
  
  
  CONCLUSIONS
  Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure.
  
  
  CONCLUSIONS
  Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion.
authors.affiliation: Environmental and Molecular Epidemiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709.
authors.forename: J A
authors.initials: JA
authors.lastname: Taylor
authors.forename: D P
authors.initials: DP
authors.lastname: Sandler
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: D L
authors.initials: DL
authors.lastname: Shore
authors.forename: E D
authors.initials: ED
authors.lastname: Ball
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.forename: O R
authors.initials: OR
authors.lastname: McIntyre
authors.forename: E
authors.initials: E
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003062:Codon / Q000187:drug effects / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D007948:Leukemia, Monocytic, Acute / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D015479:Leukemia, Myelomonocytic, Acute / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016273:Occupational Exposure
chemical_list: D003062:Codon