Grant Details
Grant Number: |
5R01CA075311-02 Interpret this number |
Primary Investigator: |
Mulvihill, John |
Organization: |
University Of Pittsburgh At Pittsburgh |
Project Title: |
Ecogenetics of Pancreatic Cancer-Family Registry |
Fiscal Year: |
1998 |
Abstract
DESCRIPTION: Pancreatic cancer, mostly adenocarcinoma of the exocrine
pancreas, is the 5th leading cause of cancer deaths, totalling an estimated
26,300 new cases and 27,800 deaths in 1996. Survival is abysmal and no
early screening methods are currently available. Suspected environmental
determinants include tobacco use, various occupational exposures, high
dietary fat intake, and perhaps ionizing radiation. Suspected genetic
determinants include somatic mutations in the oncogene k-ras and various
chromosome regions (1p, 3p, 6q, 8p, and 17p, seen cytogenetically; 5q, 8p,
1p33, and 11q13, seen by loss of genetic heterogeneity), and rare Mendelian
conditions (e.g., hereditary pancreatitis, hereditary dysplastic nevus
syndrome, hereditary nonpolyposis colorectal cancer, hereditary heart and
ovarian cancer due to BRCA2, and the Li-Fraumeni cancer family syndrome).
Family studies, using the proposed strategy have previously yielded insights
into the origins of various cancers, including colorectal, breast, and
sarcoma; the same approach is likely to be useful in pancreatic cancer.
Specific Aim 1 is to update familial aggregations of adenocarcinoma of the
pancreas. A national registry of families with pancreatic cancer has been
initiated and the plans in this application are for updating the 71 current
families and 13 provisional families, and adding new ones to a total 150
within 4 years. Environmental and medical questionnaires will be completed
for pancreatic cancer patients and a control. Specific Aim 2 is to acquire
biologic specimens from registered families and maintain a specimen
repository. The history of all cancers will be documented with medical
records; slides, tissue blocks, DNA and sera will be assembled on available
patients and their first degree relatives. Specific Aim 3 is to conduct
preliminary analyses and assays on registry material. Collaborations will
be struck to conduct pilot work on the specimens (viz., for mutations in
TP53, BRCA2, activated k-ras and other oncogenes, dinucleotide repeats
instability, cytogenetics, and review of histopathology). Serial sera from
first degree relatives, who can be considered at increased risk, will be
assayed for a battery of tumor markers, including CEA, CA125, CA19-9, and
CA242, to prospectively detect pre-symptomatic cancer.
Publications
None