DIFFERENT GENETIC PATHWAYS TO PROXIMAL AND DISTAL COLORECTAL-CANCER INFLUENCED BY SEX-RELATED FACTORS

Mutations in the k-ras and TP53 genes, as well as microsatellite insta bility (MIN), are frequent genetic alterations in colorectal carcinoma s and represent 3 different mechanisms in the carcinogenic process. Bo th the incidence of colorectal cancer and the frequency of genetic alt erations in such tumours have been related to different clinico-pathol ogical variables, including age and gender of the patient and location of the tumour, A number of studies have also reported associations be tween different types of genetic alterations. We therefore wanted to e xplore the relationship between these genetic and clinico-pathological variables using multivariate analysis on material from 282 colorectal carcinomas, Three logistic regression models were constructed: I) the presence of K-ras mutations was dependent on MIN and age and gender o f patient, with an especially low frequency among younger males and in tumours with MIN (overall p = 0.0003); 2) the presence of TP53 mutati ons was only dependent on tumour location, with a positive association to cancers occurring distally (p = 0.002); and 3) the presence of MIN was dependent on age, gender and K-ros and TP53 mutations, as well as on tumour location, MIN was most frequent among younger male and olde r female patients, was rare in tumours with K-ros or TP53 mutations an d was found almost exclusively in the proximal colon (overall P < 0.00 01), Our data confirm that different genetic pathways to colorectal ca ncer dominate in the proximal and distal segments of the bowel and sug gest that the K-ros-and MIN-dependent pathways are influenced by diffe rent sex-related factors. (C) 1997 Wiley-Liss, Inc.