Demonstration of the need for end point validation of putative biomarkers: failure of aberrant crypt foci to predict colon cancer incidence.
Seven-week-old Sprague-Dawley rats were fed a semipurified AIN76 diet and were given a weekly injection of the colon carcinogen 1,2-dimethylhydrazine for 8 weeks (initiation stage of carcinogenesis). The rats were divided into seven groups and each group of rats was placed on one of seven different modifications of the AIN76 diet for the next 24 weeks (promotional stage of carcinogenesis). The mean numbers of aberrant crypt foci/rat and the incidence of adenocarcinomas from some of the seven dietary groups were found to be significantly different. However, all attempts to show a significant correlation between the mean number of aberrant crypt foci/rat and the incidence of adenocarcinomas failed. Therefore, the number of aberrant crypt foci/rat cannot by itself be used as a reliable quantitative predictor (biomarker) of the efficacy of dietary intervention or of chemopreventive procedures on modulating the risk of developing colon cancer. This conclusion emphasizes the need for end point validation of potential cancer biomarkers before the biomarkers can be considered predictive of modulation of the risk for colon cancer.
Hardman
W E
WE
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
Cameron
I L
IL
Heitman
D W
DW
Contreras
E
E
D000230:Adenocarcinoma / Q000139:chemically induced*; D000704:Analysis of Variance; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000139:chemically induced*; D003314:Corn Oil / Q000008:administration & dosage; D004032:Diet; D004127:Dimethylhydrazines; D008297:Male; D010368:Pectins / Q000008:administration & dosage; D011379:Prognosis; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis
D004127:Dimethylhydrazines; D003314:Corn Oil; D010368:Pectins