Sugimura H, Caporaso N E, Modali R V, Hoover R N, Resau J H, Trump B F, Longergan J A, Krontiris T G, Mann D L, Weston A
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892.
Cancer Res. 1990 Mar 15;50(6):1857-62.
The hypothesis that rare variable nucleotide tandem repeat alleles of the Ha-ras-1 polymorphism are an inherited predisposing factor in human lung carcinogenesis has been evaluated in an age, race, and smoking matched case-control study. Twenty-three different alleles were identified by their restriction fragment length in DNA isolated from peripheral blood lymphocytes and were categorized into three groups: common; intermediate; and rare. The frequencies of rare alleles in blacks with either squamous cell carcinoma, large cell carcinoma, or small cell carcinoma were found to be significantly higher than those among groups of control subjects that were comprised of chronic obstructive pulmonary disease patients and patients with cancer at sites other than the lung. A similar trend which did not reach statistical significance was observed in whites. These data are consistent with the hypothesis that inheritance of Ha-ras-1 rare restriction fragment length alleles represents a genetic risk factor for some human lung cancers. The biological basis of this observation remains to be clarified, and it is possible that ethnic variations in rare allele frequencies are responsible for the differences noted. However, the data suggest that further evaluation of the Ha-ras-1 polymorphism as a marker of individual lung cancer susceptibility is warranted.
在一项年龄、种族和吸烟情况相匹配的病例对照研究中，对Ha-ras-1基因多态性的罕见可变核苷酸串联重复等位基因是人类肺癌发生的遗传易患因素这一假说进行了评估。通过从外周血淋巴细胞中分离的DNA的限制性片段长度鉴定出23种不同的等位基因，并将其分为三组：常见型；中间型；和罕见型。发现患有鳞状细胞癌、大细胞癌或小细胞癌的黑人中罕见等位基因的频率显著高于由慢性阻塞性肺疾病患者和肺部以外部位癌症患者组成的对照组。在白人中观察到了类似趋势，但未达到统计学显著性。这些数据与以下假说一致，即Ha-ras-1罕见限制性片段长度等位基因的遗传代表了某些人类肺癌的遗传危险因素。这一观察结果的生物学基础仍有待阐明，罕见等位基因频率的种族差异可能是导致所观察到差异的原因。然而，数据表明有必要进一步评估Ha-ras-1基因多态性作为个体肺癌易感性标志物的情况。
