SOMATIC MUTATIONS, ACETYLATOR STATUS, AND PROGNOSIS IN COLORECTAL-CANCER

Background-Somatic mutations in K-ras and TP53 may be associated with both acetylator status and prognosis in colorectal cancer. Aims-To det ermine whether cancers with somatic mutations are more frequent in fas t acetylators and whether mutations or acetylator status influence pro gnosis after colorectal surgery. Patients-One hundred consecutive subj ects undergoing elective surgery for colorectal cancer. Methods-Acetyl ator status was determined by polymerase chain reaction (PCR) genotypi ng for polymorphism in the N-acetyltransferase 2 (NAT2) gene. Mutation s in K-ras (codon 12) and TP53 were determined by PCR analysis using r estriction enzyme digestion and single strand conformation polymorphis m respectively. Survival from colorectal cancer for up to five years a fter diagnosis was analysed using the Kaplan-Meier product limit estim ator. Cox proportional hazards regression was used to compare survival rates after adjusting for tumour stage. Results-Mutations in K-ras an d TP53 were independent of acetylator status. By log rank test, surviv al was significantly reduced in subjects with TP53 mutations (p=0.003) but was not significantly related to acetylator status or the presenc e of K-ras mutations. After adjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95% confi dence interval 1.5 to 11.6) when compared with that of a TP53 negative reference group. Conclusion-The presence of both TP53 and K-ras mutat ions in colorectal tumours is an adverse prognostic marker which is in dependent of tumour stage.