Increased Risk of Incident Pancreatic Cancer Among First-degree Relatives of Patients with Familial Pancreatic Cancer

• Published in: Clinical cancer research Vol. 7; no. 3; pp. 738 - 744
• Main Authors: Tersmette, A C, Petersen, G M, Offerhaus, G J, Falatko, F C, Brune, K A, Goggins, M, Rozenblum, E, Wilentz, R E, Yeo, C J, Cameron, J L, Kern, S E, Hruban, R H
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-03-2001
• Subjects: Age Factors; Aged; Family Health; Female; Humans; Male; Middle Aged; Models, Statistical; Pancreatic Neoplasms - epidemiology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Registries; Risk; Time Factors
• ISSN: 1078-0432; 1557-3265

It has been estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of patients with
pancreatic cancer (PC). The quantified prospective risk of PC among first-degree relatives of PC patients has not been investigated.
Families enrolled in the National Familial Pancreas Tumor Registry (NFPTR) prior to September 1, 1998 were followed to estimate
the risk and incidence of PC among first-degree relatives of patients with PC. Analyses were performed separately on kindreds
with at least two first-degree relatives with PC (familial pancreatic carcinoma (PC); n = 150) at the time the kindred was enrolled in the NFPTR and on kindreds without a pair of affected first-degree relatives
(sporadic PC; n = 191). A subanalysis was performed on familial PC kindreds containing three or more affected members at the time of enrollment
in the NFPTR ( n = 52). Risk was estimated by comparing observed new cases of PC during the observation period with expected numbers based
on the United States population-based Surveillance, Epidemiology and End Results program data. Incidence was estimated using
person-years risk analyses. During the observational period, six incident PCs developed in the first-degree relatives: two
in the sporadic PC kindreds, and four in the familial PC kindreds. The PC risk in the sporadic PC kindreds was not significantly
greater than expected [observed/expected = 6.5 (95% CI = 0.78–23.3)] with an incidence rate of 24.5/10 5 /year. There was a significantly increased 18-fold risk (95% CI = 4.74–44.5) of PC among first-degree relatives in familial
PC kindreds, with an incidence of 76.0/10 5 /year. In the subset of familial PC kindreds with three or more affected family members at the time of enrollment, there was
a 57-fold (95% CI = 12.4–175) increased risk of PC and an incidence of 301.4/10 5 /year compared with the Surveillance, Epidemiology and End Result age-adjusted incidence of PC in the U.S. (8.8/10 5 /year). When stratified by age, the risk was largely confined to relatives over the age of 60. This study is the first analysis
of incident PC occurring in familial PC kindreds. The risk and incidence of PC is exceptionally high among at-risk first-degree
relatives in familial PC kindreds in which at least three first-degree relatives have already been diagnosed with PC. Familial
PC kindreds are a reasonable high-risk group for PC screening and chemoprevention research.