Pancreatic cancer represents the fourth most common cause of cancer-related mortality. Nonetheless, relatively little is known about the pathogenesis and epidemiology of this malignancy. In a previous R01 grant (R01CA86102), we pooled the resources of three large prospective cohort studies, the Nurses'Health Study, the Health Professionals Follow-up Study, and the Physician's Health Study to examine the epidemiology and pathogenesis of pancreatic cancer. In response to a NIH Program Announcement, PA-05- 040, """"""""Molecular Approaches to Diet and Pancreatic Cancer Prevention,"""""""" we now propose to extend our findings and our collaborations by including the resources of two additional large prospective cohort studies with extensive banked dietary data and biospecimens, the Women's Health Study and the Women's Health Initiative. Pooling of cases from these five large ongoing prospective cohort studies with long-term follow-up will allow a rigorous examination of hypotheses focusing on mechanisms of pancreatic cancer pathogenesis. We propose to examine 3 inter-related pathogenic pathways for pancreatic carcinogenesis: 1) energy balance, insulin and insulin-like growth factor signaling, 2) inflammation, and 3) vitamin D-related pathways. With the combined resources of these five cohort studies, we will study relevant exposures utilizing (1) prospectively collected data on diet, body habitus, physical activity, analgesic use, and other exposures (2) nutrient and hormonal biomarkers, and (3) genetic factors relevant to the pathways of interest. These exposures, plasma biomarkers, and genetic factors will be examined in relation to pancreatic cancer incidence as well as specific molecular alterations in pancreatic cancer specimens. The prospective design of these analyses will allow a rigorous examination of these risk factors while minimizing the potential biases that are inherent in retrospective studies of pancreatic cancer. By better understanding underlying mechanisms, dose-response relations, inter-relations among factors acting in similar pathways, variation in response due to genetic susceptibility, and specificity in associations to specific tumor markers, we can identify recommendations aimed at reducing the incidence and mortality from this highly lethal malignancy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Mahabir, Somdat
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dana-Farber Cancer Institute
United States
Zip Code
Saha, Supriya K; Zhu, Andrew X; Fuchs, Charles S et al. (2016) Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise. Oncologist 21:594-9
Yuan, Chen; Clish, Clary B; Wu, Chen et al. (2016) Circulating Metabolites and Survival Among Patients With Pancreatic Cancer. J Natl Cancer Inst 108:djv409
Yuan, Chen; Qian, Zhi Rong; Babic, Ana et al. (2016) Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival. J Clin Oncol 34:2899-905
(2015) Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types. J Natl Cancer Inst 107:djv279
Genkinger, J M; Kitahara, C M; Bernstein, L et al. (2015) Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies. Ann Oncol 26:2257-66
Machiela, Mitchell J; Zhou, Weiyin; Sampson, Joshua N et al. (2015) Characterization of large structural genetic mosaicism in human autosomes. Am J Hum Genet 96:487-97
Yuan, Chen; Rubinson, Douglas A; Qian, Zhi Rong et al. (2015) Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus. J Clin Oncol 33:29-35
Campa, Daniele; Rizzato, Cosmeri; Stolzenberg-Solomon, Rachael et al. (2015) TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. Int J Cancer 137:2175-83
Fuchs, C S; Azevedo, S; Okusaka, T et al. (2015) A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Ann Oncol 26:921-7
Childs, Erica J; Mocci, Evelina; Campa, Daniele et al. (2015) Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet 47:911-6

Showing the most recent 10 out of 49 publications