Cancer Control Research
5R01CA040641-16
Burt, Randall W.
HIGH RISK FAMILIAL COLON CANCER--GENETICS AND PHENOTYPE
AbstractDESCRIPTION: (Adapted from Applicant's Abstract). The overall objective of
this renewal is to determine the genetic etiology and clinical
characteristics of high risk familial colon cancer. High risk familial
colon cancer accounts for 10 to 20% of colon cancer cases. It is defined
when there are two first degree relatives with colon cancer or a single case
diagnosed at an age <50 years. Family members in this situation are at
three- to six-fold increased risk for colon cancer and special screening has
been recommended. Some fraction of these high risk cases arise from
hereditary non-polyposis colorectal cancer (HNPCC), familial adenomatous
polyposis (FAP) or attenuated adenomatous polyposis coli (AAPC), but most do
not. The fraction of high risk cases that arise from FAP, AAPC and HNPCC
will first be determined by identifying all high risk cases in the Utah
Population Data Base, a data base that combines Utah cancer and genealogy
resources. Records and archival tissues will be used to find which of these
high risk individuals has FAP (records) and which has HNPCC or AAPC (genetic
diagnosis). High risk cases that do not have one of these syndromes will
then serve as index cases to select a number of suitable kindreds for
further study. Kindreds will be expanded and kindred members will undergo
colonoscopy to define the polyp and cancer phenotype. Linkage analysis will
then be done to identify new polyp and cancer susceptibility loci. A
precise clinical and genetic definition of this high risk familial category
is needed so that affected families can be accurately identified, screened
and managed, and so that genetic screening and testing for the rare
syndromes and for additional susceptibility loci can be applied widely in
this group.
|