p53 mutations and occupational exposures in a surgical series of lung cancers.
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.
Harty
L C
LC
Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Guinee
D G
DG
Travis
W D
WD
Bennett
W P
WP
Jett
J
J
Colby
T V
TV
Tazelaar
H
H
Trastek
V
V
Pairolero
P
P
Liotta
L A
LA
Harris
C C
CC
Caporaso
N E
NE
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*
D015342:DNA Probes; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53