Assessment of “Gene-Environment” Interaction in Cases of Familial and Sporadic Pancreatic Cancer
Theresa P. Yeo*1, Ralph H. Hruban2, Alison P. Klein2, Kieran Brune2, Charles J. Yeo3
1School of Nursing, Thomas Jefferson University, Philadelphia, PA; 2Department of Pathology, Johns Hopkins University, Baltimore, MD; 3Department of Surgery, Thomas Jefferson University, Philadelphia, PA
Introduction: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. This study characterizes one of the largest national registries of familial PC (FPC) and sporadic PC (SPC), focusing on demographics, clinical factors, self-reported environmental and occupational lifetime exposures and survival status.Background: Reported risk factors for PC include: advancing age, a family history of PC, high-risk inherited syndromes, cigarette smoking, exposure to occupational and environmental carcinogens, African-American race, high fat/high cholesterol diet, obesity, chronic pancreatitis, and diabetes mellitus.
Methods: This retrospective cross-sectional, case-only analysis includes cases of FPC (n = 569) and SPC (n = 689) from the Johns Hopkins National Familial Pancreas Tumor Registry (NFPTR) enrolled between 1994 and 2005.
Results: Significant findings include: 1) Mild, multiplicative interaction between family history of PC and exposure to asbestos, environmental radon, and environmental tobacco smoke (ETS) (Odds Ratios > 1.0). 2) Non-smoker ETS exposed cases were diagnosed at a significantly younger mean age (64.0 years) than non-smoker non-ETS exposed cases (66.5 years) (p < 0.0004). 3) FPC smokers with ETS exposure were diagnosed at a significantly (p = 0.05) younger mean age (63.7 years) compared to FPC non-smokers without ETS exposure (66.6.years). 4) Mean age at diagnosis for Ashkenazi Jewish SPC subjects was significantly younger (by 2.1 years) than Ashkenazi Jewish FPC cases (p = 0.05). 5) Ashkenazi Jewish FPC subjects who smoked were diagnosed 5.9 years earlier than Ashkenazi Jewish FPC non-smokers (p = 0.05). 6) Median survival for unresected FPC cases was significantly shorter (168 days) compared to unresected SPC cases (200 days) (p = 0.04),survival significantly improved to 713 days for FPC cases and 727 days for SPC cases after surgical resection.
Conclusions: These are the first data to show that occupational and environmental exposures may act synergistically with inherited or acquired genetic polymorphisms, resulting in earlier occurrence of PC. Exposure to cigarette smoking and ETS is associated with a younger mean age of diagnosis in FPC and SPC cases and those with an Ashkenazi Jewish heritage, compared to non-exposed cases. These results imply that unaffected individuals from families with a history of PC who smoke, have had early life ETS exposure, or have certain occupational and environmental exposures may benefit from screening and early identification of pre-malignant lesions.