Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer

Anne C. Tersmette, Gloria M. Petersen, G. Johan A. Offerhaus, Florence C. Falatko, Kieran A. Brune, Michael Goggins, Ester Rozenblum, Robb E. Wilentz, Charles J. Yeo, John L. Cameron, Scott E. Kern, Ralph H. Hruban

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247 Scopus citations

Abstract

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, 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 24.5/105/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 76.0/105/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 301.4/105/year compared with the Surveillance, Epidemiology and End Result age-adjusted incidence of PC in the U.S. (8.8/105/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.

Original languageEnglish (US)
Pages (from-to)738-744
Number of pages7
JournalClinical Cancer Research
Volume7
Issue number3
StatePublished - 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tersmette, A. C., Petersen, G. M., Offerhaus, G. J. A., 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. (2001). Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clinical Cancer Research, 7(3), 738-744.