Harty L C, Guinee D G, Travis W D, Bennett W P, Jett J, Colby T V, Tazelaar H, Trastek V, Pairolero P, Liotta L A, Harris C C, Caporaso N E
Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer Epidemiol Biomarkers Prev. 1996 Dec;5(12):997-1003.
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.
p53突变在恶性肺肿瘤中很常见。在之前接受过p53突变评估的88例接受手术治疗的吸烟者肺癌中，45例肿瘤（51.1%）在外显子5 - 8中有突变（D.G. Guinee, Jr.等人，《癌变（伦敦）》，16: 993 - 1002, 1995）。我们在此报告了与这些p53突变相关的13种职业暴露和13种高危职业的研究情况。两种分子异常与职业暴露有关：（a）编码（非转录）链上的G:C→T:A颠换（n = 13）与铬酸盐暴露及金属行业就业有关（P < 0.05），与镍暴露有边缘关联（P = 0.056）；（b）非CpG位点的G:C→A:T转换（n = 9）与石化行业工作有关（P = 0.05）。未发现p53突变与性别、吸烟包年数、肿瘤组织学、诊断时年龄或肺癌家族史之间存在关联。由于所有三名接触铬酸盐的受试者都患有表现出G:C→T:A编码链颠换的大细胞癌，对该暴露队列的随访应能阐明与p53基因的关联。
