Somatic mutations, acetylator status, and prognosis in colorectalcancer

Background—Somatic mutations inK-ras and TP53 may be associated with bothacetylator status and prognosis in colorectal cancer.
Aims—To determine whether cancers withsomatic mutations are more frequent in fast acetylators and whethermutations or acetylator status influence prognosis after colorectal surgery.
Patients—One hundred consecutive subjectsundergoing elective surgery for colorectal cancer.
Methods—Acetylator status was determined bypolymerase chain reaction (PCR) genotyping for polymorphism in theN-acetyltransferase 2 (NAT2) gene. Mutations in K-ras(codon 12) and TP53 were determined by PCR analysisusing restriction enzyme digestion and single strand conformationpolymorphism respectively. Survival from colorectal cancer for up tofive years after diagnosis was analysed using the Kaplan-Meier productlimit estimator. Cox proportional hazards regression was used tocompare survival rates after adjusting for tumour stage.
Results—Mutations in K-ras andTP53 were independent of acetylator status. By log ranktest, survival was significantly reduced in subjects with TP53mutations (p=0.003) but was not significantly related toacetylator status or the presence of K-ras mutations. Afteradjustment for tumour stage, subjects with both TP53 and K-ras mutations had a 4.2-fold case fatality (95%confidence interval 1.5 to 11.6) when compared with that of aTP53 negative reference group.
Conclusion—The presence of both TP53and K-ras mutations in colorectal tumours is an adverseprognostic marker which is independent of tumour stage.

Keywords:colorectal cancer; TP53 andK-ras mutations; acetylator status; prognosis