Assessment of "gene-environment" interaction in cases of familial pancreatic cancer as compared to cases of sporadic pancreatic cancer.
Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. Known risk factors include advancing age, family history of PC, high-risk inherited syndromes, cigarette smoking, exposure to occupational and environmental carcinogens, and African-American race. Other risk factors associated with the development of PC include high fat/high cholesterol diet, obesity, chronic pancreatitis, diabetes mellitus, and a history of cholecystectomy.; Objectives. The goals of this research study were to examine the relationship between the following occupational and environmental exposures and pancreatic cancer (PC): cigarette smoking, environmental tobacco smoke exposure (ETS), usual occupation, and occupational and environmental exposures. Comparisons between mean age at diagnosis with regard to gender, Ashkenazi Jewish heritage, smoking, ETS exposure, and occupational categories and exposures, as well as two-year survival rates in cases with familial PC (FPC) (n = 569), defined as having two affected first-degree relatives with PC, and cases with sporadic PC (SPC) (n = 689), one first degree relative with PC, were analyzed and described in this study.; Methods. A retrospective cross-sectional, case-only analysis (n = 1258) of secondary data obtained from the Johns Hopkins the National Familial Pancreas Tumor Registry (NFPTR) data was conducted to test hypotheses. Independent variables included: demographic, cigarette smoking, environmental tobacco smoke (ETS) exposure, as well as occupation and occupational exposure variables. The outcomes of interest (dependent variables) included mean at diagnosis and survival analysis.; Results. The following exposures: asbestos, radiation, heavy wood dust, arsenic, environmental radon, ETS exposure between the ages of 41 and 60 years (alone or with asbestos exposure) demonstrated mild, multiplicative interaction with a family history of PC, with ORs greater than 1.0, when entered into models as a single independent variable or as an interaction terms. Overall the SPC group (84.16%) reported significantly more lifetime ETS exposure than did the FPC group (78.95%, p = 0.02). Men with PC were 66.0% more likely to be smokers than women with PC, and 78.0% more likely to be regular smokers (p = <0.0004).; The mean age at diagnosis was 64.5 years in the FPC group and 63.8 years in the SPC group. In sporadic Ashkenazi Jewish subjects, the mean age at diagnosis in cases was significantly (p = 0.05) younger, by 2.1 years, than in familial Ashkenazi Jewish cases. Of note, the Ashkenazi subjects with FPC were compared by smoking status, those who smoked were diagnosed 5.9 years earlier than FPC Ashkenazi non-smokers (p = 0.05). ETS exposure differed significantly, (p < 0.0004) between the FPC and SPC groups in the following age strata: 21 years of age or younger and ages of 41 to 60 years: a younger mean age at diagnosis in both groups (FPC 59.6 years & 61.2 years and SPC 56.7 years & 59.5 years, respectively) was identified. Non-smokers who reported any lifetime ETS exposure were diagnosed at a mean age (64.0 years) significantly younger than the reference group of non-smokers (66.5 years) with no reported ETS exposure (p < 0.0004). FPC smokers also reporting ETS exposure were diagnosed at a significantly (p = 0.05) younger mean age (63.7 years) as compared to FPC non-smokers (66.6.years) who did not report any ETS exposure.; The median survival for unresected FPC cases was significantly ( p = 0.04) shorter (168 days) compared to unresected SPC cases (200 days). Following surgical resection, median survival improved to 713 days for FPC cases and >730 days for SPC cases. Overall, SPC cases had a survival advantage compared to FPC cases, regardless of resection status, although the margin narrowed as survival approached 2 years.; Conclusions and implications. Occupational and environmental exposures may interact with inherited or acquired genetic polymorphisms synergistically, r......
, Theresa Pluth.
【作者单位】: The Johns Hopkins University.
【关 键 词】: Assessment of "gene-environment" interaction in cases of familial pancreatic cancer as compared to cases of sporadic pancreatic cancer.
【授予学位单位】: The Johns Hopkins University.
【学科】: Health Sciences, Public Health.; Environmental Sciences.; Health Sciences, Oncology.
【上篇论文】: 学术学位 - Investigation of atmospheric particle-bound reactive oxidative species (ROS): Their sources, characterization, and measurement.
【下篇论文】: 学术学位 - Regulation issues and prediction of natural estrogen loads for wastewater treatment plants.