Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States, and 95% of patients who develop pancreatic cancer die from their disease. Unfortunately, relatively little is known about the pathogenesis and epidemiology of this under-studied malignancy. To address this problem, the current proposal focuses on the investigation of dietary, genetic and biochemical risk factors for pancreatic cancer.
For Aim 1, I will examine a novel dietary index that estimates long-term systemic insulin exposure and two hormones altered in states of obesity and insulin resistance, adiponectin and leptin.
For Aim 2, I will investigate plasma markers of inflammation, Helicobacter pylori infection, and telomere length, in an effort to better understand the link between chronic inflammation and, pancreatic cancer risk.
For Aim 3, I will expand on recent observations linking heterogeneity at the ABO blood group locus with plasma inflammatory markers and the risk of pancreatic cancer. A major strength of this proposal is the ability to examine these factors prospectively, thereby avoiding the problems associated with retrospective analyses of pancreatic cancer epidemiology. Moreover, this proposal will assemble one of the largest prospective case-control sets to date, establishing a unique database of pancreatic cancer cases and matched controls, with repeated dietary and lifestyle assessments over several decades, archived blood specimens, and genomic DNA. This resource will allow me to rigorously examine multiple inter-related pathways with robust power. In addition, it will allow me to rapidly examine new hypotheses as they emerge. Finally, this award will enable me to develop advanced skills in biostatistics and epidemiology, pursue a focused program in pancreatic cancer research, and receive close, long-term mentorship from experienced and successful clinical researchers, promoting my transition to an independent investigator.

Public Health Relevance

Although pancreatic cancer is the 4th most common cause of cancer-related death in the U.S., we know little about predisposing factors for this disease. With the current proposal, I hope to advance our understanding of pancreatic cancer pathogenesis, generate an important resource to evaluate future hypotheses, and provide data to support recommendations for reducing mortality from this highly lethal malignancy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA140790-04
Application #
8315739
Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
Project Start
2009-09-11
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$178,110
Indirect Cost
$13,193
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Mayers, Jared R; Wu, Chen; Clish, Clary B et al. (2014) Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 20:1193-8
Wolpin, Brian M; Rubinson, Douglas A; Wang, Xiaoxu et al. (2014) Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist 19:637-8
Wolpin, Brian M; Bass, Adam J (2014) Managing advanced colorectal cancer: have we reached the PEAK with current therapies? J Clin Oncol 32:2200-2
Wu, Chen; Kraft, Peter; Stolzenberg-Solomon, Rachael et al. (2014) Genome-wide association study of survival in patients with pancreatic adenocarcinoma. Gut 63:152-60
Wolpin, Brian M; Rizzato, Cosmeri; Kraft, Peter et al. (2014) Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 46:994-1000
Rubinson, Douglas A; Hochster, Howard S; Ryan, David P et al. (2014) Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients. Invest New Drugs 32:113-22
Yuan, Chen; Bao, Ying; Wu, Chen et al. (2013) Prediagnostic body mass index and pancreatic cancer survival. J Clin Oncol 31:4229-34
Wolpin, Brian M; Ng, Kimmie; Zhu, Andrew X et al. (2013) Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. Oncologist 18:377-8
Bao, Ying; Giovannucci, Edward L; Kraft, Peter et al. (2013) A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. J Natl Cancer Inst 105:95-103
Wolpin, Brian M; Bao, Ying; Qian, Zhi Rong et al. (2013) Hyperglycemia, insulin resistance, impaired pancreatic *-cell function, and risk of pancreatic cancer. J Natl Cancer Inst 105:1027-35

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