• Lynch, Henry T. (PI)

Project: Research project

Project Details


Hereditary nonpolyposis colorectal cancer (HNPCC) poses a major
public health problem wherein very little is known about the
gross, microscopic, or histochemical premorbid pathology of the
colonic mucosa in at risk patients. We shall take advantage of our
resource of well-documented HNPCC kindreds to select 100
patients between the ages of 30 and 50 who are at 50% risk for
this disease. Each of these individuals will undergo colonoscopy
with multiple mucosal biopsies from cecum to rectum. Similar
studies will be obtained on 100 patients with nonfamilial colon
cancer and 20 normal controls with negative family histories of
colon cancer. Detailed biochemical (lectin binding, tritiated
thymidine uptake) and histopathologic (dysplastic changes,
adenomatous changes, alterations in mucin secretion) parameters
will be assessed in these tissues in a double-binded manner.
Concurrently we will provide intensive education about the
natural history of HNPCC and our strategies for surveillance and
management of these patients and their relatives for their family
physicians as well as followup as to the effect of such
intervention. OUr experimental design will provide a basis for
statistical analysis of the study population, the comparison group,
and normal controls, utilizing the SYSDAT data analysis program
for discriminant analysis to drive the function(s) that best
differentiates cancer affected individuals from controls. That
function will then be applied to the at risk group in order to
determine if this group is heterogeneous and regard to the
pathologic variables,and if there is bimodality of the discriminant
score in the at risk group. These methods will allow comparison
of the various parameters studies between the at risk, affected,
and normal controls. We believe that this project could provide
abundant new information as to the spectrum of premalignant
abnormalities in HNPCC. These findings, coupled with education
and surveillance programs, could have significant implications for
cancer etiology, carcinogenesis, and control for the general
Effective start/end date5/1/8710/31/90


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


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