Abstract
Most inherited cancer syndromes are characterized by the familial clustering of cancers at several organ sites. To determine if cancers, other than pancreatic cancer, cluster in pancreatic cancer kindreds, we examined mortality patterns among the relatives of National Familial Pancreatic Tumor Registry probands. Over 200,000 person-years of follow-up from 8,564 first-degree relatives of probands and 1,007 spouse controls were included in these analyses. We compared mortality rates of National Familial Pancreatic Tumor Registry participants to US population rates using weighed standardized mortality ratios (wSMR). Analyses were stratified by family history of pancreatic cancer (sporadic versus familial), family history of young onset pancreatic cancer (<50 years), and family history score. Cancer mortality was increased in both the relatives of sporadic probands [wSMR 1.55, 95% confidence interval (95% CI) 1.39-1.73] and familial probands (wSMR 1.41, 95% CI 1.26-1.58). Relatives of familial probands had a significantly increased risk of dying from breast (wSMR 1.66, 95% CI 1.15-2.34), ovarian (wSMR 2.05, 95% CI 1.10-3.49), and bile duct cancers (wSMR 2.89, 95% CI 1.04-6.39). Relatives of sporadic probands were at increased risk of dying from bile duct cancer (wSMR 3.01, 95% CI 1.09-6.67). Relatives of young onset probands were at higher risk of dying from cancers of the breast (wSMR 1.98, 95% CI 1.01-3.52), colon (wSMR 2.31, 95% CI 1.30-3.81) and prostate (wSMR 2.31, 95% CI 1.14-4.20). Increased cancer mortality was not observed in the spouse controls. Our results show that relatives of pancreatic cancer patients are at higher risk of developing cancers at other sites and highlight the importance of complete family history in clinical risk assessment.