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Grant Details

Grant Number: 5R03CA089726-02 Interpret this number
Primary Investigator: Holly, Elizabeth
Organization: Univ Of California At San Francisco
Project Title: Mthfr Polymorphisms in Pancreatic Cancer in Sf Bay Area
Fiscal Year: 2002
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Abstract

The capacity for DNA repair is essential to maintain both genetic integrity and normal cellular function and to control abnormal cell growth. Folate is required for biosynthesis of oligonucleotides needed for DNA repair mechanisms and inadequate folate has been associated with human cancer. The methylenetetrahydrofolate reductase (MTHFR) enzyme is critical in the regulation of folate and methionine metabolism. Because folate is important in DNA synthesis, repair and methylation, it may play a role in cancer prevention and recent evidence suggests that this is the case. The overall goal of this study is to determine whether the prevalence of the C677T and A1298C polymorphisms in the MTHTR gene differs between pancreatic cancer patients and control subjects. DNA will be examined from 334 cases and 966 control participants who had blood drawn in the large population-based case-control study that included 550 pancreatic cancer patients and 1600 controls. All genetic testing will be done using the UCSF Comprehensive Cancer Center Genome Core facilities and laboratory personnel. Data analyses for the variables collected in the interviews in the large study and for the MTHFR genetic component also will be completed variables collected in the interviews in the large study and for the MTHFR genetic component also will be completed under the proposed work. The specific aims are to: 1) identify and compare the incidence of MTHFR C677T and A1298C polymorphisms in pancreatic cancer patients and control subjects; 2) evaluate the relationships between MTHFR polymorphisms and other exposures that also may be related to risk for pancreatic cancer such as dietary folate, smoking and alcohol consumption; and 3) perform analyses of other dietary factors and other data collected in the parent study. Data will be analyzed using stratification and multiple logistic regression for all risk factors that could potentially confound or modify the association between the MTHFR polymorphisms and pancreatic cancer such as dietary folate, smoking and alcohol consumption. Data from other risk factors also will be analyzed. While a relationship between low serum folate and risk for pancreatic has been reported there is no data to describe polymorphisms in MTHFR genes among pancreatic cancer patients and control subjects. These questionnaire- and genetics-based analyses will provide new and provocative data of public health importance for this devastating disease.

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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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Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.
Authors: Chan JM, Gong Z, Holly EA, Bracci PM
Source: Nutr Cancer, 2013;65(1), p. 157-64.
PMID: 23368926
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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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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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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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Genetic variation in CYP17A1 and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California.
Authors: Duell EJ, Holly EA, Kelsey KT, Bracci PM
Source: Int J Cancer, 2010 Feb 1;126(3), p. 790-5.
PMID: 19642097
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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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Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case-control study.
Authors: Chan JM, Wang F, Holly EA
Source: Cancer Causes Control, 2009 Aug;20(6), p. 835-46.
EPub date: 2009 Mar 11.
PMID: 19277880
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Detecting pathway-based gene-gene and gene-environment interactions in pancreatic cancer.
Authors: Duell EJ, Bracci PM, Moore JH, Burk RD, Kelsey KT, Holly EA
Source: Cancer Epidemiol Biomarkers Prev, 2008 Jun;17(6), p. 1470-9.
PMID: 18559563
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Whole grains and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area, California.
Authors: Chan JM, Wang F, Holly EA
Source: Am J Epidemiol, 2007 Nov 15;166(10), p. 1174-85.
EPub date: 2007 Sep 18.
PMID: 17881383
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Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California.
Authors: Chan JM, Wang F, Holly EA
Source: Cancer Causes Control, 2007 Dec;18(10), p. 1153-67.
EPub date: 2007 Sep 1.
PMID: 17805983
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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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Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma.
Authors: Duell EJ, Casella DP, Burk RD, Kelsey KT, Holly EA
Source: Cancer Epidemiol Biomarkers Prev, 2006 Apr;15(4), p. 726-31.
PMID: 16614115
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Anthropometric factors and pancreatic cancer in a population-based case-control study in the San Francisco Bay area.
Authors: Eberle CA, Bracci PM, Holly EA
Source: Cancer Causes Control, 2005 Dec;16(10), p. 1235-44.
PMID: 16215874
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Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area.
Authors: Chan JM, Wang F, Holly EA
Source: Cancer Epidemiol Biomarkers Prev, 2005 Sep;14(9), p. 2093-7.
PMID: 16172215
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Reproductive and menstrual risk factors for pancreatic cancer: a population-based study of San Francisco Bay Area women.
Authors: Duell EJ, Holly EA
Source: Am J Epidemiol, 2005 Apr 15;161(8), p. 741-7.
PMID: 15800266
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Signs and symptoms of pancreatic cancer: a population-based case-control study in the San Francisco Bay area.
Authors: Holly EA, Chaliha I, Bracci PM, Gautam M
Source: Clin Gastroenterol Hepatol, 2004 Jun;2(6), p. 510-7.
PMID: 15181621
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