{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:17:26Z","timestamp":1791260246840,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":4925,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1993,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated point mutational activation of the <jats:italic>ras<\/jats:italic> genes (K\u2010<jats:italic>ras<\/jats:italic> codons 12, 13 and 61; N\u2010<jats:italic>ras<\/jats:italic> codons 12, 13 and 61; H\u2010<jats:italic>ras<\/jats:italic> codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K\u2010<jats:italic>ras<\/jats:italic> mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N\u2010<jats:italic>ras<\/jats:italic> or H\u2010<jats:italic>ras<\/jats:italic> mutations were found. The highest frequency of K\u2010<jats:italic>ras<\/jats:italic> 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\u2010in addition to the highly significant association between the adenocarcinoma type of lung cancer and K\u2010<jats:italic>ras<\/jats:italic> mutation\u2010a clear association of K\u2010<jats:italic>ras<\/jats:italic> mutations with heavy life\u2010time smoking (\u226550 pack\u2010years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2 \u2010 19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non\u2010significant, OR of 2.2 (90% CI 0.6 \u2010 8.7) with the presence of K\u2010<jats:italic>ras<\/jats:italic> mutation. We conclude that the occurrence of K\u2010<jats:italic>ras<\/jats:italic> mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life\u2010time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.<\/jats:p>","DOI":"10.1002\/ijc.2910530213","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T23:27:34Z","timestamp":1171927654000},"page":"250-256","source":"Crossref","is-referenced-by-count":117,"title":["K\u2010<i>ras<\/i> mutations in human adenocarcinoma of the lung: Association with smoking and occupational exposure to asbestos"],"prefix":"10.1002","volume":"53","author":[{"given":"K.","family":"Husgafvel\u2010Pursiainen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hackman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ridanp\u00e4\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Anttila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Karjalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Partanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Taikina\u2010Aho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Heikkil\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Vainio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_1_2_1","unstructured":"Alexandrov K. Rojas M. Geneste O. Castegnaro M. Camus A.\u2010M. Petruzelli S. Giuntini G.andBartsch H. An improved fluorometric assay for dosimetry of benzo(a)pyrene diol epoxide\u2010DNA adducts in smokers' lung: comparisons with total bulky adducts and AHH activity. Cancer Res. (1992). (In press)."},{"key":"e_1_2_1_3_1","first-page":"412","volume-title":"Asbestos\u2010related malignancy","author":"Antman K.","year":"1987"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1990.tb01848.x"},{"key":"e_1_2_1_5_1","first-page":"4682","article-title":"ras oncogenes in human cancer: a review","volume":"49","author":"Bos J. L.","year":"1989","journal-title":"Cancer Res."},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910500610"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870040102"},{"key":"e_1_2_1_8_1","first-page":"5410","article-title":"Genetic alterations of the p53 gene are a feature of malignant mesotheliomas","volume":"51","author":"Cote R. J.","year":"1991","journal-title":"Cancer Res."},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1991.tb24469.x"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1905840"},{"issue":"2","key":"e_1_2_1_11_1","first-page":"18","article-title":"ras and p53 mutation in smoking\u2010related human lung cancers with and without asbestos exposure","volume":"70","author":"Husgafvel\u2010Pursiainen K.","year":"1992","journal-title":"Pharmacol. Toxicol."},{"key":"e_1_2_1_12_1","first-page":"244","volume-title":"Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Tobacco smoking","author":"IARC","year":"1986"},{"key":"e_1_2_1_13_1","series-title":"IARC Scientific Publication 100","volume-title":"Cancer: causes, occurrence and control","author":"IARC","year":"1990"},{"key":"e_1_2_1_14_1","series-title":"IARC Scientific Publication 116","volume-title":"Mechanisms of carcinogenesis in risk identification","author":"IARC","year":"1992"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","unstructured":"Karjalainen A. Anttila S. Heikkil\u00e4 L. Karhunen P.andVainio H. Asbestos exposure among Finnish lung cancer patients. Occupational history and fiber concentration in lung tissue. Amer. J. indust. Med. (1992). (In press).","DOI":"10.1002\/ajim.4700230309"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1991.tb24468.x"},{"key":"e_1_2_1_17_1","first-page":"719","article-title":"Statistical aspects of the analysis of data from retrospective studies of disease","volume":"22","author":"Mantel N.","year":"1959","journal-title":"J. nat. Cancer Inst."},{"key":"e_1_2_1_18_1","first-page":"2610","article-title":"p53 and Kirsten\u2010ras mutations in human mesothelioma cell lines","volume":"52","author":"Metcalf R. A.","year":"1992","journal-title":"Cancer Res."},{"key":"e_1_2_1_19_1","first-page":"1353","article-title":"Mutations of ras genes distinguish a subset of non\u2010small\u2010cell lung cancer cell lines from small\u2010cell lung cancer cell lines","volume":"6","author":"Mitsudomi T.","year":"1991","journal-title":"Oncogene"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.4.1085"},{"key":"e_1_2_1_21_1","first-page":"5738","article-title":"Incidence and possible clinical significance of K\u2010ras oncogene activation in adenocarcinoma of the lung","volume":"48","author":"Rodenhuis S.","year":"1988","journal-title":"Cancer Res."},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2448875"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1979.tb18711.x"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/9.7.1159"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/83.14.1024"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199008303230902"},{"key":"e_1_2_1_27_1","first-page":"734","article-title":"p53 mutations in non\u2010small cell lung cancer in Japan. Associations between mutations and smoking","volume":"52","author":"Suzuki H.","year":"1992","journal-title":"Cancer Res."},{"key":"e_1_2_1_28_1","unstructured":"Taikina\u2010Aho O. Anttila S. P\u00e4\u00e4kk\u00f6 P. Sivonen S. J.andKalliom\u00e4ki P.\u2010L. Environmental pulmonary mineral burden correlated with smoking pulmonary emphysema and lung cancer. Proceedings of the VIIth International Pneumoconiosis Conference DHHS (NIOSH) Publication 90\u2010108 Pittsburgh PA Part II pp.1077\u20131082 (1990)."},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90866-2"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","unstructured":"Vainio H. Husgafvel\u2010Pursiainen K. Anttila S. Karjalainen A. Hackman P.andPartanen T. Interaction between smoking and asbestos in human lung adenocarcinoma\u2010role of K\u2010rasmutations. Environ. Hlth Persp. (1992). (In press).","DOI":"10.2307\/3431724"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(86)90335-5"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.4700210214"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.9.3070"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.2910530213","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.2910530213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:19:28Z","timestamp":1695878368000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.2910530213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,1,21]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1993,1,21]]}},"alternative-id":["10.1002\/ijc.2910530213"],"URL":"https:\/\/doi.org\/10.1002\/ijc.2910530213","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,1,21]]}}}