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

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 patien ts has not been investigated, Families enrolled in the National Familial Pa ncreas Tumor Registry (NFPTR) prior to September 1, 1998 were followed to e stimate the risk and incidence of PC among first-degree relatives of patien ts with PC, Analyses were performed separately on kindreds with at least tw o first-degree relatives with PC (familial pancreatic carcinoma (PC); n = 1 50) at the time the kindred was enrolled in the NFPTR and on kindreds witho ut a pair of affected first-degree relatives (sporadic PC; n = 191), A suba nalysis was performed on familial PC kindreds containing three or more affe cted members at the time of enrollment in the NFPTR Or = 52), Risk was esti mated by comparing observed new cases of PC during the observation period w ith expected numbers based on the United States population-based Surveillan ce, Epidemiology and End Results program data. Incidence was estimated usin g person-years risk analyses, During the observational period, six incident PCs developed in the first-degree relatives: two in the sporadic PC kindre ds, and four in the familial PC kindreds, The PC risk in the sporadic PC ki ndreds 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 fi rst-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. 3-175) increased risk of PC and an incidence of 301.4/10(5)/year compared w ith 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 larg ely confined to relatives over the age of 60. This study is the first analy sis of incident PC occurring in familial PC kindreds, The risk and incidenc e of PC is exceptionally high among at-risk first-degree relatives in famil ial PC kindreds in which at least three first-degree relatives have already been diagnosed with PC. Familial PC kindreds are a reasonable high-risk gr oup for PC screening and chemoprevention research.