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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA089726-01
Application #
6287261
Study Section
Subcommittee G - Education (NCI)
Program Officer
Verma, Mukesh
Project Start
2001-01-03
Project End
2002-12-31
Budget Start
2001-01-03
Budget End
2001-12-31
Support Year
1
Fiscal Year
2001
Total Cost
$73,750
Indirect Cost
Name
University of California San Francisco
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lujan-Barroso, Leila; Zhang, Wei; Olson, Sara H et al. (2016) Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4). Pancreas 45:1401-1410
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
Waterhouse, M; Risch, H A; Bosetti, C et al. (2015) Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. Ann Oncol 26:1776-83
Tang, Hongwei; Wei, Peng; Duell, Eric J et al. (2014) Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis. Cancer Epidemiol Biomarkers Prev 23:98-106
Bosetti, C; Rosato, V; Li, D et al. (2014) Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol 25:2065-72
Klein, Alison P; Lindström, Sara; Mendelsohn, Julie B et al. (2013) An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PLoS One 8:e72311
Chan, June M; Gong, Zhihong; Holly, Elizabeth A et al. (2013) Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Nutr Cancer 65:157-64
Olson, Sara H; Hsu, Meier; Satagopan, Jaya M et al. (2013) Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. Am J Epidemiol 178:691-700
Bosetti, C; Lucenteforte, E; Bracci, P M et al. (2013) Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 24:2903-10
Bosetti, C; Lucenteforte, E; Silverman, D T et al. (2012) Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 23:1880-8

Showing the most recent 10 out of 40 publications