Familial Risk of Pancreatic Cancer

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Abstract
Background: Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United States. Although smoking and age are known risk factors for pancreatic cancer, several case reports and case–control studies have suggested that there is also a familial risk. We evaluated whether a family history of pancreatic cancer increases the risk of pancreatic cancer in first-degree relatives and whether smoking and younger age at cancer diagnosis further increase this risk. Methods: We conducted in-person interviews with 247 patients (“case probands”) with pancreatic cancer and 420 population-based control probands to collect risk factor data and pancreatic cancer family history for 1816 first-degree relatives of the case probands and 3157 first-degree relatives of the control probands. We analyzed the data by unconditional logistic regression models, with adjustment for correlated data by use of generalized estimating equations. All statistical tests were two-sided. Results: A positive family history of pancreatic cancer (i.e., being related to a case proband) or ever-smoking cigarettes approximately doubled the risk of pancreatic cancer (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR = 2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI = 2.18 to 31.07) for relatives who ever smoked and were related to a case proband who was diagnosed before age 60 years. Conclusion: Routine questioning of patients about a family history of pancreatic cancer, the age of onset of this cancer in their relatives, and the patient's smoking status may identify individuals at high risk of pancreatic cancer. Future research exploring the genetic and environmental interactions associated with the risk of pancreatic cancer is critically important.