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Grant Details

Grant Number: 5R01CA109767-05 Interpret this number
Primary Investigator: Holly, Elizabeth
Organization: University Of California, San Francisco
Project Title: Molecular Epidemiology of Pancreatic Cancer
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): This application is 100% related to PC. Recent studies show that factors associated with abnormal glucose metabolism are important in PC development. We hypothesize that insulin resistance (IR) is a growth-promoting factor in PC etiology. Also, genetic variation in insulin, glucose, and lipid metabolism and in candidate genes for IR are related to PC risk. A clinic-based case-control study will include 600 patients and 600 controls obtained from UCSF clinics. Detailed history of diet, body mass index, obesity, physical activity, diabetes and other factors including medication use and smoking will be collected during interviews. Blood will be collected from eligible participants. UCSF's Molecular Epidemiology Core will process all bloods and extract DMA for use in molecular/ genetic studies. SNPs will be examined in candidate genes related to IR and metabolism, and lipid metabolism. Genetic testing will be done using UCSF's Genome Core facilities and personnel. Main effects for exposures and SNPs will be evaluated as will gene-environment and gene-gene interactions when sample sizes permit. We will work with NCI on the PC consortium development and combine new data with data from our earlier population-based PC study (N=2,233) to conduct analyses. We will collaborate with Seattle and Mayo clinic PC studies to pool data and increase power to study rare exposures and factors within small groups. Major strengths are: 1. Large number of PC cases will allow analyses by sex, ethnicity and race; 2. Innovative hypotheses to advance PC research (e.g. SNPs); 3. Expertise of lab faculty and facilities; 4. No proxy interviews; 5. Clinic-based cases will diminish case loss due to poor survival; 6. Studies of diabetes, IR, diet, obesity, physical activity and SNPs are innovative and new to large studies of PC; 7. Blood samples will be banked for future genetic studies and data will be pooled for greater statistical power.

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Publications

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.
Authors: Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, Bracci PM, Neale RE, Muscat J, Anderson K, Gallinger S, Olson SH, Miller AB, Bas Bueno-de-Mesquita H, Scelo G, Janout V, Holcatova I, Lagiou P, Serraino D, Lucenteforte E, Fabianova E, Ghadirian P, Baghurst PA, Zatonski W, Foretova L, Fontham E, Bamlet WR, Holly EA, Negri E, Hassan M, Prizment A, Cotterchio M, Cleary S, Kurtz RC, Maisonneuve P, Trichopoulos D, Polesel J, Duell EJ, Boffetta P, La Vecchia C
Source: Ann Oncol, 2014 Oct;25(10), p. 2065-72.
EPub date: 2014 Jul 23.
PMID: 25057164
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Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis.
Authors: Tang H, Wei P, Duell EJ, Risch HA, Olson SH, Bueno-de-Mesquita HB, Gallinger S, Holly EA, Petersen GM, Bracci PM, McWilliams RR, Jenab M, Riboli E, Tjønneland A, Boutron-Ruault MC, Kaaks R, Trichopoulos D, Panico S, Sund M, Peeters PH, Khaw KT, Amos CI, Li D
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jan;23(1), p. 98-106.
EPub date: 2013 Oct 17.
PMID: 24136929
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An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
Authors: Klein AP, Lindström S, Mendelsohn JB, Steplowski E, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Lacroix A, Li D, Mandelson MT, Olson SH, Petersen GM, Risch HA, Stolzenberg-Solomon RZ, Zheng W, Amundadottir L, Albanes D, Allen NE, Bamlet WR, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, Duell EJ, Elena J, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hassan M, Hutchinson A, Hunter DJ, Kooperberg C, Kurtz RC, Liu S, Overvad K, Palli D, Patel AV, Rabe KG, Shu XO, Slimani N, Tobias GS, Trichopoulos D, Van Den Eeden SK, Vineis P, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Chanock SJ, Hoover RN, Hartge P, Kraft P
Source: PLoS One, 2013;8(9), p. e72311.
EPub date: 2013 Sep 13.
PMID: 24058443
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Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Bosetti C, Lucenteforte E, Bracci PM, Negri E, Neale RE, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Holly EA, Gao YT, Yu H, Kurtz RC, Cotterchio M, Maisonneuve P, Zeegers MP, Duell EJ, Boffetta P, La Vecchia C
Source: Ann Oncol, 2013 Nov;24(11), p. 2903-10.
EPub date: 2013 Aug 22.
PMID: 23970016
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Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.
Authors: Olson SH, Hsu M, Satagopan JM, Maisonneuve P, Silverman DT, Lucenteforte E, Anderson KE, Borgida A, Bracci PM, Bueno-de-Mesquita HB, Cotterchio M, Dai Q, Duell EJ, Fontham EH, Gallinger S, Holly EA, Ji BT, Kurtz RC, La Vecchia C, Lowenfels AB, Luckett B, Ludwig E, Petersen GM, Polesel J, Seminara D, Strayer L, Talamini R, Pancreatic Cancer Case-Control Consortium
Source: Am J Epidemiol, 2013 Sep 1;178(5), p. 691-700.
EPub date: 2013 Jul 2.
PMID: 23820785
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Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area.
Authors: Gong Z, Holly EA, Bracci PM
Source: Cancer Causes Control, 2012 Dec;23(12), p. 1929-37.
EPub date: 2012 Sep 27.
PMID: 23015286
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Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Duell EJ, Lucenteforte E, Olson SH, Bracci PM, Li D, Risch HA, Silverman DT, Ji BT, Gallinger S, Holly EA, Fontham EH, Maisonneuve P, Bueno-de-Mesquita HB, Ghadirian P, Kurtz RC, Ludwig E, Yu H, Lowenfels AB, Seminara D, Petersen GM, La Vecchia C, Boffetta P
Source: Ann Oncol, 2012 Nov;23(11), p. 2964-70.
EPub date: 2012 Jul 5.
PMID: 22767586
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Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.
Authors: Li D, Duell EJ, Yu K, Risch HA, Olson SH, Kooperberg C, Wolpin BM, Jiao L, Dong X, Wheeler B, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross M, Hartge P, Hoover RN, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Mandelson MT, Petersen G, Zheng W, Agalliu I, Albanes D, Boutron-Ruault MC, Bracci PM, Buring JE, Canzian F, Chang K, Chanock SJ, Cotterchio M, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hoffman Bolton JA, Hunter DJ, Hutchinson A, Jacobs KB, Jenab M, Khaw KT, Kraft P, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Patel AV, Rabe KG, Riboli E, Shu XO, Tjønneland A, Tobias GS, Trichopoulos D, Virtamo J, Visvanathan K, Watters J, Yu H, Zeleniuch-Jacquotte A, Amundadottir L, Stolzenberg-Solomon RZ
Source: Carcinogenesis, 2012 Jul;33(7), p. 1384-90.
EPub date: 2012 Apr 20.
PMID: 22523087
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Serum autoantibodies to pancreatic cancer antigens as biomarkers of pancreatic cancer in a San Francisco Bay Area case-control study.
Authors: Bracci PM, Zhou M, Young S, Wiemels J
Source: Cancer, 2012 Nov 1;118(21), p. 5384-94.
EPub date: 2012 Apr 19.
PMID: 22517435
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Mitochondrial DNA sequence variation and risk of pancreatic cancer.
Authors: Lam ET, Bracci PM, Holly EA, Chu C, Poon A, Wan E, White K, Kwok PY, Pawlikowska L, Tranah GJ
Source: Cancer Res, 2012 Feb 1;72(3), p. 686-95.
EPub date: 2011 Dec 15.
PMID: 22174369
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Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms.
Authors: Bracci PM
Source: Mol Carcinog, 2012 Jan;51(1), p. 53-63.
PMID: 22162231
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Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).
Authors: Bosetti C, Lucenteforte E, Silverman DT, Petersen G, Bracci PM, Ji BT, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Bertuccio P, Gao YT, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Boffetta P, La Vecchia C
Source: Ann Oncol, 2012 Jul;23(7), p. 1880-8.
EPub date: 2011 Nov 21.
PMID: 22104574
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Survival in population-based pancreatic cancer patients: San Francisco Bay area, 1995-1999.
Authors: Gong Z, Holly EA, Bracci PM
Source: Am J Epidemiol, 2011 Dec 15;174(12), p. 1373-81.
EPub date: 2011 Nov 1.
PMID: 22047824
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Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Lucenteforte E, La Vecchia C, Silverman D, Petersen GM, Bracci PM, Ji BT, Bosetti C, Li D, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Gao YT, Negri E, Hassan M, Cotterchio M, Su J, Maisonneuve P, Boffetta P, Duell EJ
Source: Ann Oncol, 2012 Feb;23(2), p. 374-82.
EPub date: 2011 May 2.
PMID: 21536662
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Cigarette, cigar and pipe smoking, passive smoke exposure, and risk of pancreatic cancer: a population-based study in the San Francisco Bay Area.
Authors: Tranah GJ, Holly EA, Wang F, Bracci PM
Source: BMC Cancer, 2011 Apr 15;11, p. 138.
EPub date: 2011 Apr 15.
PMID: 21496267
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Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Bertuccio P, La Vecchia C, Silverman DT, Petersen GM, Bracci PM, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham ET, Bamlet WR, Holly EA, Lucenteforte E, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Bosetti C, Boffetta P
Source: Ann Oncol, 2011 Jun;22(6), p. 1420-6.
EPub date: 2011 Jan 18.
PMID: 21245160
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Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies.
Authors: Li D, Tang H, Hassan MM, Holly EA, Bracci PM, Silverman DT
Source: Cancer Causes Control, 2011 Feb;22(2), p. 189-97.
EPub date: 2010 Nov 21.
PMID: 21104117
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Vitamin D, calcium, and retinol intake, and pancreatic cancer in a population-based case-control study in the San Francisco Bay area.
Authors: Zablotska LB, Gong Z, Wang F, Holly EA, Bracci PM
Source: Cancer Causes Control, 2011 Jan;22(1), p. 91-100.
EPub date: 2010 Nov 12.
PMID: 21072578
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Risk of pancreatic cancer by alcohol dose, duration, and pattern of consumption, including binge drinking: a population-based study.
Authors: Gupta S, Wang F, Holly EA, Bracci PM
Source: Cancer Causes Control, 2010 Jul;21(7), p. 1047-59.
EPub date: 2010 Mar 27.
PMID: 20349126
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Intake of fatty acids and antioxidants and pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.
Authors: Gong Z, Holly EA, Wang F, Chan JM, Bracci PM
Source: Int J Cancer, 2010 Oct 15;127(8), p. 1893-904.
PMID: 20104522
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Pancreatitis and pancreatic cancer in two large pooled case-control studies.
Authors: Bracci PM, Wang F, Hassan MM, Gupta S, Li D, Holly EA
Source: Cancer Causes Control, 2009 Nov;20(9), p. 1723-1731.
PMID: 19760029
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Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case-control study.
Authors: Gong Z, Holly EA, Bracci PM
Source: Cancer Causes Control, 2009 Oct;20(8), p. 1317-25.
EPub date: 2009 May 5.
PMID: 19415507
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Pancreatic cancer and medical history in a population-based case-control study in the San Francisco Bay Area, California.
Authors: Ko AH, Wang F, Holly EA
Source: Cancer Causes Control, 2007 Oct;18(8), p. 809-19.
EPub date: 2007 Jul 14.
PMID: 17632765
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Diabetes mellitus and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California.
Authors: Wang F, Gupta S, Holly EA
Source: Cancer Epidemiol Biomarkers Prev, 2006 Aug;15(8), p. 1458-63.
PMID: 16896032
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