Pancreatic cancer is the fourth-leading cause of cancer death in men and fifth in women, with greater than 30,000 deaths annually in the United States. According to data from the Surveillance, Epidemiology, and End Results (SEER) database, approximately 20% of cases affect people under the age of 60, hereafter termed young-onset pancreatic cancer. The investigators propose to define the factors influencing risk for young-onset pancreatic cancer utilizing the core resource from the Pancreatic Cancer SPORE program at the Mayo Clinic. This database consists of risk-factor questionnaires, medical records, blood, and surgical specimens. From these available materials, assessments will be made regarding the impact of known and as yet unknown contributions to risk for the development of pancreatic cancer. Initial evidence from the applicant's work and the published literature is presented in this application which suggests that familial cancer syndromes, inherited forms of pancreatitis, and DNA repair abnormalities may each explain a proportion of the young-onset cases. We propose to investigate the contribution of these factors to risk for young-onset pancreatic cancer. Frequency of mutations in BRCA2, CDKN2A (Familial Melanoma), Fanconi Anemia Genes (FANCC and FANCG), CFTR, SPINK1, PRSS1, and polymorphisms of several DNA repair genes will be determined among 500 young-onset cases versus 1000 older-onset cases and 1000 healthy controls. The composition to the SPORE resource enables thorough examination of these candidate genes in the context of environmental and behavioral factors. The principal investigator, Dr. Robert McWilliams, has clinical training in medical oncology, and post-doctoral training in the genetic epidemiology of cancer. This grant will enable him to elucidate the contributors to young-onset pancreatic cancer and establish himself as an independent investigator in the genetic epidemiology of cancer. This proposed research is 100% relevant to pancreatic cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Academic/Teacher Award (ATA) (K07)
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Study Section
Subcommittee G - Education (NCI)
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Perkins, Susan N
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Mayo Clinic, Rochester
United States
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McWilliams, Robert R; Wieben, Eric D; Chaffee, Kari G et al. (2018) CDKN2A Germline Rare Coding Variants and Risk of Pancreatic Cancer in Minority Populations. Cancer Epidemiol Biomarkers Prev 27:1364-1370
McWilliams, Robert R; Maisonneuve, Patrick; Bamlet, William R et al. (2016) Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis. Pancreas 45:311-6
McCleary-Wheeler, Angela L; McWilliams, Robert; Fernandez-Zapico, Martin E (2012) Aberrant signaling pathways in pancreatic cancer: a two compartment view. Mol Carcinog 51:25-39
McWilliams, Robert R; Wieben, Eric D; Rabe, Kari G et al. (2011) Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. Eur J Hum Genet 19:472-8
McWilliams, Robert R; Matsumoto, Martha E; Burch, Patrick A et al. (2010) Obesity adversely affects survival in pancreatic cancer patients. Cancer 116:5054-62
McWilliams, Robert R; Petersen, Gloria M; Rabe, Kari G et al. (2010) Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma. Cancer 116:203-9
McWilliams, Robert R; Bamlet, William R; de Andrade, Mariza et al. (2009) Nucleotide excision repair pathway polymorphisms and pancreatic cancer risk: evidence for role of MMS19L. Cancer Epidemiol Biomarkers Prev 18:1295-302
McWilliams, Robert R; Bamlet, William R; de Andrade, Mariza et al. (2009) Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev 18:2549-52
McWilliams, Robert R; Bamlet, William R; Cunningham, Julie M et al. (2008) Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. Cancer Res 68:4928-35
McWilliams, Robert R; Bamlet, William R; Rabe, Kari G et al. (2006) Association of family history of specific cancers with a younger age of onset of pancreatic adenocarcinoma. Clin Gastroenterol Hepatol 4:1143-7