MTHFR POLYMORPHISMS IN PANCREATIC CANCER IN SF BAY AREA

Summary

Principal Investigator: ELIZABETH HOLLY
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.
Funding Period: 2001-01-03 - 2003-12-31
more information: NIH RePORT

Top Publications

  1. pmc Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis
    Hongwei Tang
    Authors Affiliations Departments of Gastrointestinal Medical Oncology and Epidemiology, The University of Texas MD Anderson Cancer Center Division of Biostatistics and Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas Catalan Institute of Oncology ICO IDIBELL, Barcelona, Spain Yale University School of Public Health, New Haven, Connecticut Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York National Institute for Public Health and the Environment RIVM, Bilthoven and Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Samuel Lunenfeld Research Institute, Toronto General Hospital, University of Toronto, Toronto, Canada Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota International Agency for Research on Cancer, Lyon Institut national de la santé et de la recherche medicale INSERM, Centre for Research in Epidemiology and Population Health CESP, U1018, Nutrition, Hormones and Women s Health team Univ Paris Sud, UMRS 1018 IGR, F 94805, Villejuif, France Division of Epidemiology, Public Health, and Primary Care, Imperial College London, Suwa Red Cross Hospital
    Cancer Epidemiol Biomarkers Prev 23:98-106. 2014
  2. pmc Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)
    E J Duell
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology ICO IDIBELL, Barcelona, Spain
    Ann Oncol 23:2964-70. 2012
  3. pmc Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area
    Zhihong Gong
    Department of Epidemiology and Biostatistics, University of California San Francisco, 3333 California Street, Suite 280, San Francisco, CA 94118 1944, USA
    Cancer Causes Control 23:1929-37. 2012
  4. ncbi Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area
    June M Chan
    Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94158 9001, USA
    Nutr Cancer 65:157-64. 2013
  5. pmc Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium
    Sara H Olson
    Department of Epidemiology and Biostatistics, 307 East 63rd Street, New York, NY 10065, USA
    Am J Epidemiol 178:691-700. 2013
  6. pmc Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4)
    C Bosetti
    Department of Epidemiology, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Milan
    Ann Oncol 24:2903-10. 2013
  7. pmc An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population
    Alison P Klein
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
    PLoS ONE 8:e72311. 2013
  8. pmc Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)
    C Bosetti
    Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Ann Oncol 23:1880-8. 2012
  9. pmc Cigarette, cigar and pipe smoking, passive smoke exposure, and risk of pancreatic cancer: a population-based study in the San Francisco Bay Area
    Gregory J Tranah
    California Pacific Medical Center Research Institute, 94107, USA
    BMC Cancer 11:138. 2011
  10. pmc Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)
    E Lucenteforte
    Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri Milan, Milan, Italy
    Ann Oncol 23:374-82. 2012

Scientific Experts

  • Paige M Bracci
  • Zhihong Gong
  • Samir Gupta
  • Gregory J Tranah
  • D Li
  • JUNE ML CHAN
  • Eric J Duell
  • Lydia B Zablotska
  • C Bosetti
  • Elizabeth A Holly
  • E Lucenteforte
  • Sara H Olson
  • P A Baghurst
  • M Cotterchio
  • W Zatonski
  • P Ghadirian
  • H B Bueno-de-Mesquita
  • P Boffetta
  • S Gallinger
  • A B Miller
  • C La Vecchia
  • R Talamini
  • P Maisonneuve
  • E A Holly
  • E Negri
  • J Polesel
  • Steven Gallinger
  • Gloria M Petersen
  • H Bas Bueno-de-Mesquita
  • Y T Gao
  • E Fontham
  • R C Kurtz
  • H Yu
  • S H Olson
  • H A Risch
  • J Su
  • W R Bamlet
  • M Hassan
  • P Bertuccio
  • Hongwei Tang
  • Harvey A Risch
  • Marie Christine Boutron-Ruault
  • Dimitrios Trichopoulos
  • Michelle Cotterchio
  • Alison P Klein
  • Robert C Kurtz
  • Ernest T Lam
  • B T Ji
  • G M Petersen
  • D T Silverman
  • Furong Wang
  • Carey A Eberle
  • Elio Riboli
  • Rudolf Kaaks
  • Anne Tjønneland
  • Robert R McWilliams
  • Mazda Jenab
  • Malin Sund
  • Petra H M Peeters
  • Kay Tee Khaw
  • Peng Wei
  • Salvatore Panico
  • Christopher I Amos
  • Peter Kraft
  • Lori Strayer
  • Manal Hassan
  • Brian M Wolpin
  • Julie B Mendelsohn
  • Kristin E Anderson
  • Elizabeth H Fontham
  • Laufey Amundadottir
  • Jerry Polesel
  • Carlo La Vecchia
  • Qi Dai
  • Patrick Maisonneuve
  • Andrea LaCroix
  • Meier Hsu
  • Eric J Jacobs
  • Stephen J Chanock
  • Robert N Hoover
  • Renato Talamini
  • David J Hunter
  • William R Bamlet
  • Xiao Ou Shu
  • Emily Steplowski
  • Simin Liu
  • Rachael Z Stolzenberg-Solomon
  • Albert B Lowenfels
  • Daniela Seminara
  • Paolo Vineis

Detail Information

Publications31

  1. pmc Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis
    Hongwei Tang
    Authors Affiliations Departments of Gastrointestinal Medical Oncology and Epidemiology, The University of Texas MD Anderson Cancer Center Division of Biostatistics and Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas Catalan Institute of Oncology ICO IDIBELL, Barcelona, Spain Yale University School of Public Health, New Haven, Connecticut Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York National Institute for Public Health and the Environment RIVM, Bilthoven and Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Samuel Lunenfeld Research Institute, Toronto General Hospital, University of Toronto, Toronto, Canada Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota International Agency for Research on Cancer, Lyon Institut national de la santé et de la recherche medicale INSERM, Centre for Research in Epidemiology and Population Health CESP, U1018, Nutrition, Hormones and Women s Health team Univ Paris Sud, UMRS 1018 IGR, F 94805, Villejuif, France Division of Epidemiology, Public Health, and Primary Care, Imperial College London, Suwa Red Cross Hospital
    Cancer Epidemiol Biomarkers Prev 23:98-106. 2014
    ..Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level...
  2. pmc Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)
    E J Duell
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology ICO IDIBELL, Barcelona, Spain
    Ann Oncol 23:2964-70. 2012
    ..Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction...
  3. pmc Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area
    Zhihong Gong
    Department of Epidemiology and Biostatistics, University of California San Francisco, 3333 California Street, Suite 280, San Francisco, CA 94118 1944, USA
    Cancer Causes Control 23:1929-37. 2012
    ..However, studies of obesity and overall survival in patients with pancreatic cancer are notably lacking, especially in population-based studies...
  4. ncbi Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area
    June M Chan
    Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94158 9001, USA
    Nutr Cancer 65:157-64. 2013
    ..Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer...
  5. pmc Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium
    Sara H Olson
    Department of Epidemiology and Biostatistics, 307 East 63rd Street, New York, NY 10065, USA
    Am J Epidemiol 178:691-700. 2013
    ..There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age. ..
  6. pmc Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4)
    C Bosetti
    Department of Epidemiology, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Milan
    Ann Oncol 24:2903-10. 2013
    ..Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent...
  7. pmc An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population
    Alison P Klein
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
    PLoS ONE 8:e72311. 2013
    ..We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer...
  8. pmc Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)
    C Bosetti
    Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Ann Oncol 23:1880-8. 2012
    ..To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables...
  9. pmc Cigarette, cigar and pipe smoking, passive smoke exposure, and risk of pancreatic cancer: a population-based study in the San Francisco Bay Area
    Gregory J Tranah
    California Pacific Medical Center Research Institute, 94107, USA
    BMC Cancer 11:138. 2011
    ..To examine the influence of cigarette, cigar and pipe smoking, cessation of cigarette smoking and passive smoke exposure on the risk of pancreatic cancer...
  10. pmc Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)
    E Lucenteforte
    Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri Milan, Milan, Italy
    Ann Oncol 23:374-82. 2012
    ..Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved...
  11. pmc Survival in population-based pancreatic cancer patients: San Francisco Bay area, 1995-1999
    Zhihong Gong
    Department of Epidemiology and Biostatistics, University of California San Francisco, 3333 California Street, San Francisco, CA 94118 1944, USA
    Am J Epidemiol 174:1373-81. 2011
    ..Although the results provide further evidence of poor survival among patients with pancreatic cancer, the data also suggest that within-stage-of-disease patients survived somewhat longer with therapy...
  12. pmc Mitochondrial DNA sequence variation and risk of pancreatic cancer
    Ernest T Lam
    Institute for Human Genetics, University of California, San Francisco, California, USA
    Cancer Res 72:686-95. 2012
    ..Together, the results of this study provide evidence that aggregated common and rare variants and the accumulation of singleton variants are important contributors to pancreatic cancer risk...
  13. pmc Serum autoantibodies to pancreatic cancer antigens as biomarkers of pancreatic cancer in a San Francisco Bay Area case-control study
    Paige M Bracci
    School of Medicine, University of California San Francisco, San Francisco, CA 94118 1944, USA
    Cancer 118:5384-94. 2012
    ..Autoantibodies to tumor-associated antigens (TAAs) can be present months to years before diagnosis and hold promise as biomarkers for early detection...
  14. pmc Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer
    Donghui Li
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Carcinogenesis 33:1384-90. 2012
    ....
  15. pmc Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4)
    P Bertuccio
    Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Ann Oncol 22:1420-6. 2011
    ..Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco...
  16. ncbi Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies
    Donghui Li
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, 77030, USA
    Cancer Causes Control 22:189-97. 2011
    ....
  17. pmc Vitamin D, calcium, and retinol intake, and pancreatic cancer in a population-based case-control study in the San Francisco Bay area
    Lydia B Zablotska
    Department of Epidemiology and Biostatistics, University of California San Francisco, 3333 California Street, San Francisco, CA 94118, USA
    Cancer Causes Control 22:91-100. 2011
    ..The aim of this study was to evaluate a complex association among intake of dietary vitamin D, calcium, and retinol, and pancreatic cancer risk...
  18. pmc Risk of pancreatic cancer by alcohol dose, duration, and pattern of consumption, including binge drinking: a population-based study
    Samir Gupta
    Division of Digestive and Liver Diseases, Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 8887, USA
    Cancer Causes Control 21:1047-59. 2010
    ..Results from our detailed analyses provide support for heavy alcohol consumption (including binge drinking) as a risk factor for PCA in men...
  19. pmc Intake of fatty acids and antioxidants and pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area
    Zhihong Gong
    Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA 94118 1944, USA
    Int J Cancer 127:1893-904. 2010
    ..These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega-3 fatty acids, vitamins C and E may reduce the risk...
  20. pmc Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case-control study
    Zhihong Gong
    Division of Cancer Epidemiology, Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, 3333 California Street, Suite 280, San Francisco, CA 94118 1944, USA
    Cancer Causes Control 20:1317-25. 2009
    ..We examined the association between pancreatic cancer and intake of folate, vitamins B(6), B(12) and methionine in a large population-based case-control study...
  21. ncbi Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area
    June M Chan
    Department of Epidemiology and Biostatistics, University of California San Francisco, 94118 1944, USA
    Cancer Epidemiol Biomarkers Prev 14:2093-7. 2005
    ..These results suggest that increasing vegetable and fruit consumption, already recommended for the prevention of several other chronic diseases, may impart some protection against developing pancreatic cancer...
  22. ncbi Anthropometric factors and pancreatic cancer in a population-based case-control study in the San Francisco Bay area
    Carey A Eberle
    Department of Epidemiology and Biostatistics, University of California, 3333 California Street, Suite 280, San Francisco, CA, USA
    Cancer Causes Control 16:1235-44. 2005
    ..To investigate the association between pancreatic cancer, anthropometric factors, physical activity and caloric intake...
  23. ncbi Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma
    Eric J Duell
    Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA
    Cancer Epidemiol Biomarkers Prev 15:726-31. 2006
    ..Our results lend support for the hypothesis that proinflammatory gene polymorphisms, in combination with proinflammatory conditions, may influence the development of pancreatic cancer...
  24. ncbi Diabetes mellitus and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California
    Furong Wang
    Department of Epidemiology and Biostatistics, University of California San Francisco, Suite 280, 3333 California Street, San Francisco, CA 94118 1944, USA
    Cancer Epidemiol Biomarkers Prev 15:1458-63. 2006
    ..Diabetes has been postulated to be both a risk factor and a consequence of pancreatic cancer, but the degree of risk and associated clinical factors remain unclear...
  25. ncbi Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California
    June M Chan
    Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94118 1944, USA
    Cancer Causes Control 18:1153-67. 2007
    ..A population-based case-control study of pancreatic cancer was conducted in the San Francisco Bay Area to examine these associations...
  26. ncbi Whole grains and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area, California
    June M Chan
    Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA 94118 1944, USA
    Am J Epidemiol 166:1174-85. 2007
    ..65, 95% CI: 0.47, 0.89; trend-p = 0.02). These data provide some support for the hypothesis that consuming more whole-grain or high-fiber foods may reduce the risk of pancreatic cancer. Refined grains were not associated with risk...
  27. ncbi Detecting pathway-based gene-gene and gene-environment interactions in pancreatic cancer
    Eric J Duell
    International Agency for Research Cancer, 150 cours Albert Thomas, 69008 Lyon, France
    Cancer Epidemiol Biomarkers Prev 17:1470-9. 2008
    ....
  28. pmc Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case-control study
    June M Chan
    Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
    Cancer Causes Control 20:835-46. 2009
    ..We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk...
  29. ncbi Genetic variation in CYP17A1 and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California
    Eric J Duell
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology ICO, L Hospitalet de Llobregat, Barcelona, Spain
    Int J Cancer 126:790-5. 2010
    ..ORs for smoking and pancreatic cancer were not modified by CYP17A1 genotype. Our results suggest that the CYP17A1 A2 allele may be associated with a lower risk of pancreatic cancer in both men and women...
  30. pmc Pancreatitis and pancreatic cancer in two large pooled case-control studies
    Paige M Bracci
    Department of Epidemiology and Biostatistics, School of Medicine, University of California, 3333 California St Suite 280, San Francisco, CA 94143, USA
    Cancer Causes Control 20:1723-1731. 2009
    ..We conducted detailed analyses to determine the association between pancreatitis onset and pancreatic cancer risk...
  31. ncbi Reproductive and menstrual risk factors for pancreatic cancer: a population-based study of San Francisco Bay Area women
    Eric J Duell
    Department of Community and Family Medicine, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    Am J Epidemiol 161:741-7. 2005
    ....