Husgafvel-Pursiainen K, Hackman P, Ridanpää M, Anttila S, Karjalainen A, Partanen T, Taikina-Aho O, Heikkilä L, Vainio H
Institute of Occupational Health, Helsinki, Finland.
Int J Cancer. 1993 Jan 21;53(2):250-6. doi: 10.1002/ijc.2910530213.
We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed--in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation--a clear association of K-ras mutations with heavy life-time smoking (> or = 50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2-19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6-8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.
我们通过斑点杂交和寡核苷酸杂交技术，研究了原发性切除肺癌中ras基因（K-ras密码子12、13和61；N-ras密码子12、13和61；H-ras密码子12和61）的点突变激活情况。在所检测的48例肺肿瘤标本中，有14例（29%）发现了K-ras突变，但未发现N-ras或H-ras突变。K-ras突变在腺癌中出现的频率最高：在研究的21个样本中有12个（57%）发生了突变，这是报道的肺腺癌最高频率之一。这些肺肿瘤样本中最常见的突变类型为颠换：我们观察到11例，其中8例（占所有突变的57%）为G到T的颠换。在研究的48例患者中，大多数有大量吸烟史，无论是否有职业性接触石棉的证据。统计分析显示——除了肺癌腺癌类型与K-ras突变之间高度显著的关联外——K-ras突变与长期大量吸烟（≥50包年吸烟量；优势比（OR）4.9，90%可信区间1.2 - 19.5，多变量分析）也有明显关联。此外，职业性石棉接触与K-ras突变存在时的OR值升高，但无统计学意义，为2.2（90%可信区间0.6 - 8.7）。我们得出结论，肺腺癌中K-ras突变的发生很常见，并且这种突变与长期大量接触烟草烟雾有关，可能还与职业性接触石棉纤维有关。
