title: p53 mutations and occupational exposures in a surgical series of lung cancers.
abstract: p53 mutations are frequent in malignant lung tumors. Of 88 surgically treated lung cancers from cigarette smokers previously evaluated for p53 mutations, 45 tumors (51.1%) had mutations in exons 5-8 (D. G. Guinee, Jr. et al., Carcinogenesis (Lond.), 16: 993-1002, 1995). We report here the examination of 13 occupational exposures and 13 high-risk occupations in relation to these p53 mutations. Two molecular abnormalities were associated with occupational exposures: (a) G:C-->T:A transversions on the coding (nontranscribed) strand (n = 13) were associated with chromate exposure and employment in the metal industry (P < 0.05) and marginally associated with nickel exposure (P = 0.056); and (b) G:C-->A:T transitions at non-CpG sites (n = 9) were associated with work in the petrochemical industry (P = 0.05). No association was found between p53 mutations and gender, cigarette pack-years, tumor histology, age at diagnosis, or family history of lung cancer. Because all three chromate-exposed subjects had large cell carcinomas exhibiting G: C-->T:A coding-strand transversions, follow-up of a cohort with this exposure should clarify the association with the p53 gene.
authors.affiliation: Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Harty
authors.forename: D G
authors.initials: DG
authors.lastname: Guinee
authors.forename: W D
authors.initials: WD
authors.lastname: Travis
authors.forename: W P
authors.initials: WP
authors.lastname: Bennett
authors.forename: J
authors.initials: J
authors.lastname: Jett
authors.forename: T V
authors.initials: TV
authors.lastname: Colby
authors.forename: H
authors.initials: H
authors.lastname: Tazelaar
authors.forename: V
authors.initials: V
authors.lastname: Trastek
authors.forename: P
authors.initials: P
authors.lastname: Pairolero
authors.forename: L A
authors.initials: LA
authors.lastname: Liotta
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
authors.forename: N E
authors.initials: NE
authors.lastname: Caporaso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D004252:DNA Mutational Analysis; D015342:DNA Probes / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D016273:Occupational Exposure / Q000009:adverse effects*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D015342:DNA Probes; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53