Abstract
Purpose: Over the past 10 years there has been a growing recognition that hereditary factors are involved in the susceptibility to chronic pancreatitis (CP); however, the overall percentage of chronic pancreatitis that can be attributed as familial (defined as >2 or more first-degree relatives (FDR) with CP) is unknown. The aims of this study were to determine the proportion of CP patients with a family history (FH) of CP and the risk of CP development in FDR of probands referred to secondary and tertiary referral centers. Methods: The FH of CP from 540 CP patients (proband) and 504 unrelated controls prospectively recruited in the North American Pancreatitis Study-2 (NAPS2) dataset from 20 U.S. centers was analyzed. CP in the proband was defined by imaging or histology. CP in family members and controls was solely based on history obtained from the probands. To attempt to control for any recruitment bias, patients identified at enrollment to potentially have a genetic etiology for their CP by the patient or investigator were both excluded and included to calculate a minimum/maximum odds ratio and 95% CI. Results: See Table for breakdown of study population. Compared to controls, a CP patient was 2.3 (1.1–4.7) to 4.4 (2.3–8.2) times more likely to have at least one FDR with a history of CP. The risk for developing CP in a FDR of a CP versus a control patient was 2.5 (1.3–4.9) to 4.5 (2.5–8.2). Conclusion: 1) To the best of our knowledge this is the first report estimating the genetic contribution to chronic pancreatitis development. About 5–10% of cases in this large prospective cohort (22/413 or 52/540) could be considered familial. 2) There is approximately a 2.5 to 4.5-fold risk for a family member of a chronic pancreatitis patient to develop chronic pancreatitis. 3) Results from this study provide strong justification for identifying those genetic factors responsible for chronic pancreatis development and emphasize the importance of family history as a risk factor for chronic pancreatitis.Table: Study Population.
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