Potential roles of genetic biomarkers in colorectal cancer chemoprevention

Colorectal cancer is a significant cause of morbidity and mortality in indu strialized societies and the second most frequent cause of cancer death in the United States. Surrogate endpoint biomarkers are gaining wide acceptanc e in early diagnosis and short-term cancer chemoprevention trials in place of cancer endpoints. Molecular genetic biomarkers can be useful tools in id entifying subjects at risk of developing cancer and screening for early can cers amenable to complete cure. They may be useful both in predicting and a ssessing response to a given therapy and in determining prognosis after an initial diagnosis has been made. Ideally, biomarkers should fulfill some, i f not all, of the following criteria: variability of expression between pha ses of carcinogenesis, association with cancer risk, ability to undergo mod ification in response to a chemopreventive agent, and finally, permit ease of measurement. In consideration of colorectal cancer chemoprevention, seve ral genetic biomarkers seem to meet many of these criteria, as they do exhi bit distinct variability of expression at different phases of carcinogenesi s, are often strongly associated with increased cancer risk (especially the hereditary/familial syndromes), are generally able to be measured relative ly easily through peripheral blood sampling (germline mutations) or by colo nic mucosal sampling by endoscopic techniques (somatic mutations). In some cases, genetic biomarkers have also been demonstrated to undergo modificati on in response to a chemopreventive agent. With further understanding of th e genetic and molecular changes involved in sporadic and familial colorecta l carcinogenesis, genetic biomarkers appear to hold great potential for the identification of subjects at high risk of developing colorectal cancer, a s well as the development of novel chemopreventive approaches and form a pr omising area for further research. (C) 2000 Wiley-Liss, Inc.