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Different genetic pathways to proximal and distal colorectal cancer influenced by sex‐related factors
Author(s) -
Breivik Jarle,
Lothe Ragnhild A.,
Meling Gunn Iren,
Rognum Torleiv O.,
BørresenDale AnneLise,
Gaudernack Gustav
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971219)74:6<664::aid-ijc18>3.0.co;2-5
Subject(s) - colorectal cancer , microsatellite instability , pathological , logistic regression , medicine , cancer , mutation , incidence (geometry) , oncology , biology , cancer research , pathology , gene , genetics , allele , microsatellite , physics , optics
Mutations in the k‐ras and TP53 genes, as well as microsatellite instability (MIN), are frequent genetic alterations in colorectal carcinomas and represent 3 different mechanisms in the carcinogenic process. Both the incidence of colorectal cancer and the frequency of genetic alterations in such tumours have been related to different clinico‐pathological variables, including age and gender of the patient and location of the tumour. A number of studies have also reported associations between different types of genetic alterations. We therefore wanted to explore the relationship between these genetic and clinico‐pathological variables using multivariate analysis on material from 282 colorectal carcinomas. Three logistic regression models were constructed: 1) the presence of K‐ras mutations was dependent on MIN and age and gender of patient, with an especially low frequency among younger males and in tumours with MIN (overall p = 0.0003); 2) the presence of TP53 mutations 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‐ras and TP53 mutations, as well as on tumour location. MIN was most frequent among younger male and older female patients, was rare in tumours with K‐ras or TP53 mutations and was found almost exclusively in the proximal colon (overall p < 0.0001). Our data confirm that different genetic pathways to colorectal cancer dominate in the proximal and distal segments of the bowel and suggest that the K‐ras ‐ and MIN‐dependent pathways are influenced by different sex‐related factors. Int. J. Cancer 74:664–669, 1997.© 1997 Wiley‐Liss, Inc.