Family history of pancreatic cancer in a high-risk cancer clinic: implications for risk assessment.

Detailed family history is a critical element of cancer risk assessment. The relative importance of pancreatic cancer (PC) in a close family member, particularly in hereditary breast-ovarian syndrome (HBOS), is not clearly defined. We use a case-control design to investigate the importance of a family history of PC to cancer risk assessment. Case and control families were identified from the University of Chicago Cancer Risk database (1994-2005). Pedigrees were analyzed for personal and familial clinical cancer data. Cases included all new subjects (probands) reporting a close relative (first or second degree) with PC. Controls included the probands enrolled in the database immediately prior to and subsequent to each case (i.e. two controls for each case). From 1,231 pedigrees, 103 PC were reported by the proband in 87 unique families. Many probands reported multiple or early-onset PCs: one third (28/87) of case families met criteria for a familial PC syndrome [> or =2 first-degree relatives with PC (n = 10) or PC diagnosed < or =50 (n = 18)]. Of these families, the majority (75%) concurrently met criteria suggestive of hereditary breast-ovarian syndrome (HBOS). Because of a family history consistent with HBOS, at least one individual from each of 29 case and 55 control families underwent genetic testing for BRCA1/2. Among case families, 19 of 29 (66%) had a BRCA1/2 mutation compared with 16 of 55 (29%) controls. A significant association between family history of PC and a BRCA1/2 mutation was seen (OR 3.78, 1.32-10.9). This point estimate was strengthened but less precise in the non-Ashkenazi Jewish subset of tested families (OR 6.03, 1.68-22.14). In a high-risk population, a family history of PC, though infrequently reported, is nonetheless clinically meaningful. In risk assessment for HBOS, identifying a family history of PC should strongly raise the suspicion of an unrecognized BRCA1/2 mutation.