P53 and K-ras gene mutations in carcinoma of the rectum among Finnish women

Aims/Background-The aim of this study was to identify p53 and K-ras gene mu tations in carcinoma of the rectum among Finnish women. Mutation patterns m ight give clues to aetiological factors when comparisons are made with othe r human tumours. Methods-Of 134 women with carcinoma of the rectum, paraffin wax embedded sp ecimens of the tumour tissue were obtained from 118 patients. Genomic DNA w as extracted, and exons 4-8 of the p53 gene and codons 12/13 and 61 of the K-ras gene were amplified, and analysed for mutations by single strand conf ormation polymorphism and direct sequencing. The production of p53 and K-ra s proteins was studied by immunohistochemistry. Results-The overall crude frequency for mutations in the p53 gene was 35% b ut the true frequency appears to be higher (up to 56%). In the K-ras gene, the mutation frequency (15%) was significantly lower than that reported for colon cancer. In the p53 gene, the mutation frequency increased significan tly with patient age. In a high proportion of patients (14%) the rectal tum ours contained small subclones of tumour cells that displayed extremely rar e mutations at codons 110 and 232 of the p53 gene. Hot spot codon 175 mutat ions were significantly less common in rectal cancer than in cancer of the colon. Conclusions-Rectal cancer among Finnish women has characteristics in the mu tations of the p53 and K-ras genes that are uncommon in other human tumours , including cancer of the colon. A biological explanation of these findings is not clear at present, but might be associated with an unidentified gene tic factor in Finland.