Genetic epidemiology of pancreatic cancer

Background. Pancreatic cancer is the 5th leading cause of cancer death in the United States. The only risk factor that has been consistently associated with pancreatic cancer is cigarette smoking. Recently, studies have shown that family history of cancer or family history of pancreatic cancer are risk factors for pancreatic cancer, suggesting genetic factors may be involved in pancreatic cancer susceptibility. The primary objective of this study was to determine if there is evidence for a major gene involved in susceptibility to pancreatic cancer.; Methods. Segregation analysis was performed using family data from 287 patients treated at The Johns Hopkins Hospital and The Johns Hopkins Bayview Medical Center (collectively referred to as JHMI) between January 1, 1994 and December 30, 1999. Cigarette smoking exposure was included in the analysis to determine if it modifies putative genetic risk. An additional segregation analysis on 320 families enrolled in The National Familial Pancreatic Tumor Registry at The Johns Hopkins Hospital was performed. Analyses were performed using the REGTL program in the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) software package under both Model 1, where age-at-onset is allowed to be type-dependent and under Model 2 where susceptibility is type dependent.; Results. In our segregation analysis of 287 JHMI families, we were able to reject all non-genetic transmission models (p < 0.0001). The Mendelian models did provide an adequate fit to the data, both under Model 1 and Model 2. In our analysis of the 320 referral families enrolled in the NFPTR, all restricted models, including Mendelian and non-genetic models, were rejected under Model 1. However, in the analysis under Model 2, non-genetic models were rejected, while the Mendelian models could not be rejected.; Conclusions. These results support the hypothesis that a major gene may be involved in increased susceptibility to pancreatic cancer. Based upon the results of our hospital-based segregation analysis, we estimate that approximate 4 in every 1,000 individuals carry this high-risk allele. While cigarette smoking has been shown to be an important risk factor for pancreatic cancer in other studies, it was not a statistically significant predictor of developing pancreatic cancer in these data.