K-RAS MUTATION IN COLORECTAL-CANCER - RELATIONS TO PATIENT AGE, SEX AND TUMOR LOCATION

DNA from 251 primary tumours obtained from 123 male and 125 female Nor wegian patients with colorectal carcinoma was analysed for the presenc e of K-ras point mutations at codons 12 and 13. Mutations were found i n 99 (39%) of the samples. The frequency of K-ras mutations was signif icantly related to age and sex of the patients, and to the location of the tumours (overall: P = 0.008). K-ras mutations were much less freq uent in colonic tumours from male than female patients at younger ages (<40 years, odds ratio <0.014). The low frequency might indicate that a different, ras-indendent pathway to neoplasia is dominating in the colon of younger males. In contrast, older men had more mutations than older women (e.g. 90 years, odds ratio = 5.8). An inverse but less pr onounced relationship was seen for rectal tumours. The type of mutatio n was found to be associated to sex of patient and location of tumour. G --> C transversions accounted for 35% of the mutations in rectal tu mours from females, in contrast to only 2.5% in the rest of the materi al (P = 0.0005). This may indicate that there are specific carcinogens acting in this location.