• Lynch, Henry T. (PI)

Project: Research project

Project Details


Hereditary nonpolyposis colorectal cancer (HNPCC) is receiving major
attention throughout the world (Lynch et al; Dis Colon Rect 24:311-322,
1981) and may account for as much as 5% of all colorectal cancer, exceeding
the 1% estimate for all forms of its familial multiple adenomatous
polyposis coli counterpart. Our efforts during more than two decades has
provided many insights into this syndrome(s) which lacks premonitory
clinical signs for its diagnosis. Nevertheless, the literature reflects
much confusion with respect to its natural history, tumor spectrum, and
surveillance/management. Our purpose is to maintain and extend the largest
HNPCC family resource of its type in the world, in the hope of further
elucidating the multifaceted complexities about this disease(s). The
resource comprises 23 variably extended families wherein detailed medical
information and family histories have been compiled on approximately 4000
individuals. The work plan will include: 1) updating the pedigrees as new
cancers occur in order to more fully assess each individual's true cancer
risk; 2) provision of continued medical/genetic counselling to family
members; 3) elucidation of genetic heterogeneity with particular reference
to tumor complement in HNPCC; 4) education of both family members and their
private physicians about the risk of cancer and its highly targeted
surveillance/management strategies based upon clinical nuances of natural
history; 5) clearer biostatistical elucidation of genetic heterogeneity
with particular attention to extracolonic tumors, early age of onset,
multiple primary cancers, predilection of proximal vs. distal colonic
cancer, cutaneous signs, and increased cancer survival; and 6) assuring an
opportunity for supply of vital medical/genetic data and biological samples
to collaborating geneticists, biostatisticians, and other basic scientists
concerned with a variety of parameters which could provide clues to
biomarkers of gene carriage. A segregation analysis was done on 11
families. Both the recessive hypothesis and the hypothesis of no
transmission were rejected (p less than 0.001). The data showed a good fit
with the hypothesis of dominant transmission with variable age of onset.
This proposal will extend the initial segregation analysis and provide an
analysis of family syndromes, to determine which particular cancer
phenotypes form familial syndromes.
Effective start/end date4/1/866/30/89


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


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