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p53 Mutations in Non-Small Cell Lung Cancer in Japan: Association between Mutations and Smoking¹

Laboratories of Chemotherapy [H. S., Ta. T., R. U.], Epidemiology [T. K.], and Immunology [To. T.], Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464, Japan; Department of Internal Medicine [Y. A.] and Department of Surgery [M. S.], Aichi Cancer Center Hospital, Chikusa-ku, Nagoya 464, Japan

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.

¹ This work was supported in part by a Grant-in-Aid for the Comprehensive Ten-Year Strategy for Cancer Research from the Ministry of Health and Welfare, Japan; Grant-in-Aids for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare, Japan; a grant from the Cancer Research Institute, Inc., New York; and a grant from the Imanaga Memorial Foundation, Japan.

² To whom requests for reprints should be addressed.

Received 10/ 2/91. Accepted 12/ 4/91.

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