Grant Number:	1R03CA089726-01 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:	2001

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.




Pancreatic Cancer Risk is Modulated by Inflammatory Potential of Diet and ABO Genotype: A Consortia-based Evaluation and Replication Study.
Authors: Antwi S.O. , Bamlet W.R. , Pedersen K.S. , Chaffee K.G. , Risch H.A. , Shivappa N. , Steck S.E. , Anderson K.E. , Bracci P.M. , Polesel J. , et al. .
Source: Carcinogenesis, 2018-05-25 00:00:00.0; , .
EPub date: 2018-05-25 00:00:00.0.
PMID: 29800239
Related Citations

Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Lujan-Barroso L. , Zhang W. , Olson S.H. , Gao Y.T. , Yu H. , Baghurst P.A. , Bracci P.M. , Bueno-de-Mesquita H.B. , Foretová L. , Gallinger S. , et al. .
Source: Pancreas, 2016 Nov; 45(10), p. 1401-1410.
PMID: 27088489
Related Citations

Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis.
Authors: McWilliams R.R. , Maisonneuve P. , Bamlet W.R. , Petersen G.M. , Li D. , Risch H.A. , Yu H. , Fontham E.T. , Luckett B. , Bosetti C. , et al. .
Source: Pancreas, 2016 Feb; 45(2), p. 311-6.
PMID: 26646264
Related Citations

Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.
Authors: Waterhouse M. , Risch H.A. , Bosetti C. , Anderson K.E. , Petersen G.M. , Bamlet W.R. , Cotterchio M. , Cleary S.P. , Ibiebele T.I. , La Vecchia C. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2015 Aug; 26(8), p. 1776-83.
PMID: 25977560
Related Citations

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 G.M. , Bracci P.M. , Neale R.E. , Muscat J. , Anderson K. , Gallinger S. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2014 Oct; 25(10), p. 2065-72.
PMID: 25057164
Related Citations

Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis.
Authors: Tang H. , Wei P. , Duell E.J. , Risch H.A. , Olson S.H. , Bueno-de-Mesquita H.B. , Gallinger S. , Holly E.A. , Petersen G.M. , Bracci P.M. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2014 Jan; 23(1), p. 98-106.
PMID: 24136929
Related Citations

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Bosetti C. , Lucenteforte E. , Bracci P.M. , Negri E. , Neale R.E. , Risch H.A. , Olson S.H. , Gallinger S. , Miller A.B. , Bueno-de-Mesquita H.B. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2013 Nov; 24(11), p. 2903-10.
PMID: 23970016
Related Citations

Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.
Authors: Olson S.H. , Hsu M. , Satagopan J.M. , Maisonneuve P. , Silverman D.T. , Lucenteforte E. , Anderson K.E. , Borgida A. , Bracci P.M. , Bueno-de-Mesquita H.B. , et al. .
Source: American Journal Of Epidemiology, 2013-09-01 00:00:00.0; 178(5), p. 691-700.
EPub date: 2013-09-01 00:00:00.0.
PMID: 23820785
Related Citations

Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.
Authors: Chan J.M. , Gong Z. , Holly E.A. , Bracci P.M. .
Source: Nutrition And Cancer, 2013; 65(1), p. 157-64.
PMID: 23368926
Related Citations

An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.
Authors: Klein A.P. , Lindström S. , Mendelsohn J.B. , Steplowski E. , Arslan A.A. , Bueno-de-Mesquita H.B. , Fuchs C.S. , Gallinger S. , Gross M. , Helzlsouer K. , et al. .
Source: Plos One, 2013; 8(9), p. e72311.
PMID: 24058443
Related Citations

Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area.
Authors: Gong Z. , Holly E.A. , Bracci P.M. .
Source: Cancer Causes & Control : Ccc, 2012 Dec; 23(12), p. 1929-37.
PMID: 23015286
Related Citations

Serum autoantibodies to pancreatic cancer antigens as biomarkers of pancreatic cancer in a San Francisco Bay Area case-control study.
Authors: Bracci P.M. , Zhou M. , Young S. , Wiemels J. .
Source: Cancer, 2012-11-01 00:00:00.0; 118(21), p. 5384-94.
EPub date: 2012-11-01 00:00:00.0.
PMID: 22517435
Related Citations

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).
Authors: Duell E.J. , Lucenteforte E. , Olson S.H. , Bracci P.M. , Li D. , Risch H.A. , Silverman D.T. , Ji B.T. , Gallinger S. , Holly E.A. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2012 Nov; 23(11), p. 2964-70.
PMID: 22767586
Related Citations

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).
Authors: Bosetti C. , Lucenteforte E. , Silverman D.T. , Petersen G. , Bracci P.M. , Ji B.T. , Negri E. , Li D. , Risch H.A. , Olson S.H. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2012 Jul; 23(7), p. 1880-8.
PMID: 22104574
Related Citations

Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.
Authors: Li D. , Duell E.J. , Yu K. , Risch H.A. , Olson S.H. , Kooperberg C. , Wolpin B.M. , Jiao L. , Dong X. , Wheeler B. , et al. .
Source: Carcinogenesis, 2012 Jul; 33(7), p. 1384-90.
PMID: 22523087
Related Citations

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 G.M. , Bracci P.M. , Ji B.T. , Bosetti C. , Li D. , Gallinger S. , Miller A.B. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2012 Feb; 23(2), p. 374-82.
PMID: 21536662
Related Citations

Mitochondrial DNA sequence variation and risk of pancreatic cancer.
Authors: Lam E.T. , Bracci P.M. , Holly E.A. , Chu C. , Poon A. , Wan E. , White K. , Kwok P.Y. , Pawlikowska L. , Tranah G.J. .
Source: Cancer Research, 2012-02-01 00:00:00.0; 72(3), p. 686-95.
EPub date: 2012-02-01 00:00:00.0.
PMID: 22174369
Related Citations

Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms.
Authors: Bracci P.M. .
Source: Molecular Carcinogenesis, 2012 Jan; 51(1), p. 53-63.
PMID: 22162231
Related Citations

Survival in population-based pancreatic cancer patients: San Francisco Bay area, 1995-1999.
Authors: Gong Z. , Holly E.A. , Bracci P.M. .
Source: American Journal Of Epidemiology, 2011-12-15 00:00:00.0; 174(12), p. 1373-81.
EPub date: 2011-12-15 00:00:00.0.
PMID: 22047824
Related Citations

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 D.T. , Petersen G.M. , Bracci P.M. , Negri E. , Li D. , Risch H.A. , Olson S.H. , Gallinger S. , et al. .
Source: Annals Of Oncology : Official Journal Of The European Society For Medical Oncology / Esmo, 2011 Jun; 22(6), p. 1420-6.
PMID: 21245160
Related Citations

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 G.J. , Holly E.A. , Wang F. , Bracci P.M. .
Source: Bmc Cancer, 2011-04-15 00:00:00.0; 11, p. 138.
EPub date: 2011-04-15 00:00:00.0.
PMID: 21496267
Related Citations

Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies.
Authors: Li D. , Tang H. , Hassan M.M. , Holly E.A. , Bracci P.M. , Silverman D.T. .
Source: Cancer Causes & Control : Ccc, 2011 Feb; 22(2), p. 189-97.
PMID: 21104117
Related Citations

Vitamin D, calcium, and retinol intake, and pancreatic cancer in a population-based case-control study in the San Francisco Bay area.
Authors: Zablotska L.B. , Gong Z. , Wang F. , Holly E.A. , Bracci P.M. .
Source: Cancer Causes & Control : Ccc, 2011 Jan; 22(1), p. 91-100.
PMID: 21072578
Related Citations

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 E.A. , Wang F. , Chan J.M. , Bracci P.M. .
Source: International Journal Of Cancer, 2010-10-15 00:00:00.0; 127(8), p. 1893-904.
PMID: 20104522
Related Citations

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 E.A. , Bracci P.M. .
Source: Cancer Causes & Control : Ccc, 2010 Jul; 21(7), p. 1047-59.
PMID: 20349126
Related Citations

Genetic variation in CYP17A1 and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California.
Authors: Duell E.J. , Holly E.A. , Kelsey K.T. , Bracci P.M. .
Source: International Journal Of Cancer, 2010-02-01 00:00:00.0; 126(3), p. 790-5.
PMID: 19642097
Related Citations

Pancreatitis and pancreatic cancer in two large pooled case-control studies.
Authors: Bracci P.M. , Wang F. , Hassan M.M. , Gupta S. , Li D. , Holly E.A. .
Source: Cancer Causes & Control : Ccc, 2009 Nov; 20(9), p. 1723-1731.
PMID: 19760029
Related Citations

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 E.A. , Bracci P.M. .
Source: Cancer Causes & Control : Ccc, 2009 Oct; 20(8), p. 1317-25.
PMID: 19415507
Related Citations

Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case-control study.
Authors: Chan J.M. , Wang F. , Holly E.A. .
Source: Cancer Causes & Control : Ccc, 2009 Aug; 20(6), p. 835-46.
PMID: 19277880
Related Citations

Detecting pathway-based gene-gene and gene-environment interactions in pancreatic cancer.
Authors: Duell E.J. , Bracci P.M. , Moore J.H. , Burk R.D. , Kelsey K.T. , Holly E.A. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2008 Jun; 17(6), p. 1470-9.
PMID: 18559563
Related Citations

Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California.
Authors: Chan J.M. , Wang F. , Holly E.A. .
Source: Cancer Causes & Control : Ccc, 2007 Dec; 18(10), p. 1153-67.
PMID: 17805983
Related Citations

Whole grains and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area, California.
Authors: Chan J.M. , Wang F. , Holly E.A. .
Source: American Journal Of Epidemiology, 2007-11-15 00:00:00.0; 166(10), p. 1174-85.
EPub date: 2007-11-15 00:00:00.0.
PMID: 17881383
Related Citations

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 E.A. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2006 Aug; 15(8), p. 1458-63.
PMID: 16896032
Related Citations

Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma.
Authors: Duell E.J. , Casella D.P. , Burk R.D. , Kelsey K.T. , Holly E.A. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2006 Apr; 15(4), p. 726-31.
PMID: 16614115
Related Citations

Anthropometric Factors And Pancreatic Cancer In A Population-based Case-control Study In The San Francisco Bay Area
Authors: Eberle C.A. , Bracci P.M. , Holly E.A. .
Source: Cancer Causes & Control : Ccc, 2005 Dec; 16(10), p. 1235-44.
PMID: 16215874
Related Citations

Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area.
Authors: Chan J.M. , Wang F. , Holly E.A. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2005 Sep; 14(9), p. 2093-7.
PMID: 16172215
Related Citations

Reproductive And Menstrual Risk Factors For Pancreatic Cancer: A Population-based Study Of San Francisco Bay Area Women
Authors: Duell E.J. , Holly E.A. .
Source: American Journal Of Epidemiology, 2005-04-15 00:00:00.0; 161(8), p. 741-7.
PMID: 15800266
Related Citations

Signs And Symptoms Of Pancreatic Cancer: A Population-based Case-control Study In The San Francisco Bay Area
Authors: Holly E.A. , Chaliha I. , Bracci P.M. , Gautam M. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2004 Jun; 2(6), p. 510-7.
PMID: 15181621
Related Citations

Prior History Of Allergies And Pancreatic Cancer In The San Francisco Bay Area
Authors: Holly E.A. , Eberle C.A. , Bracci P.M. .
Source: American Journal Of Epidemiology, 2003-09-01 00:00:00.0; 158(5), p. 432-41.
PMID: 12936898
Related Citations

A Population-based Study Of The Arg399gln Polymorphism In X-ray Repair Cross- Complementing Group 1 (xrcc1) And Risk Of Pancreatic Adenocarcinoma
Authors: Duell E.J. , Holly E.A. , Bracci P.M. , Wiencke J.K. , Kelsey K.T. .
Source: Cancer Research, 2002-08-15 00:00:00.0; 62(16), p. 4630-6.
PMID: 12183419
Related Citations

A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk.
Authors: Duell E.J. , Holly E.A. , Bracci P.M. , Liu M. , Wiencke J.K. , Kelsey K.T. .
Source: Journal Of The National Cancer Institute, 2002-02-20 00:00:00.0; 94(4), p. 297-306.
PMID: 11854392
Related Citations