Weston A, Caporaso N E, Perrin L S, Sugimura H, Tamai S, Krontiris T G, Trump B F, Hoover R N, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
Environ Health Perspect. 1992 Nov;98:61-7. doi: 10.1289/ehp.929861.
Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
原癌基因（H-ras-1和L-myc）以及肿瘤抑制基因（p53）位点与肺癌发生有关。在一项病例对照研究中，正在评估这些基因位点的DNA限制性片段长度多态性，作为预测癌症风险或癌症存在时预后的标志物。病例和对照者有40包年或更长时间的吸烟史，或肺功能测试有其他异常，他们的年龄密切匹配（病例64岁，对照61岁），白种人与非裔美国人的比例接近1（病例为0.95:1.00，对照为1.00:0.88）。H-ras-1基因存在插入缺失多态性。通过MspI消化定义的罕见H-ras-1等位基因的遗传，赋予白种人患肺癌的相对风险为2.0（95%置信区间，0.5 - 7.3），非裔美国人为3.2（0.9 - 11.6）（74例病例，67例对照）。L-myc基因序列在第二和第三外显子之间存在一个限制性位点（EcoR1）多态性。据报道，限制性位点存在等位基因的遗传在日本肺癌患者中预示预后不良（存在淋巴结转移）。在病例对照研究对象（56例病例，55例对照）和另外的手术病例（40例）中对这一假设进行了检验，但在美国人群中未发现支持该假设的证据。p53基因是一种肿瘤抑制基因，其第72位残基可编码脯氨酸或精氨酸。未发现次要等位基因（脯氨酸）与肺癌诊断之间存在关联（76例病例，68例对照）。（摘要截短于250字）
