To evaluate the association of mutations in the K-ras gene with the incidence of non-small cell lung cancer (NSCLC) in Japanese patients, 410 patients treated surgically were studied. DNA was extracted from frozen specimens, and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) hybridization assay was used to examine K-ras mutations in codons 12, 13 and 61. K-ras mutations were found in 33 patients (8.0%), and all were smokers or ex-smokers. There were no significant differences in clinical or pathological stage between wild-type cases and mutant cases. The most frequently identified mutation was a G↷T transversion (25/33, 75.8%) that resulted in the substitution of a glycine for a cysteine or a valine. Previous studies have shown that the majority of K-ras mutations among smokers are G↷T transversion. In our study, K-ras mutations were found only in smokers, and there was a high frequency of G↷T transversions. A clear correlation exists between smoking and K-ras gene mutations.

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