Methylation and Oxidation in Breast Cancer Epidemiology

Summary

Principal Investigator: Jo Freudenheim
Abstract: There is considerable epidemiologic evidence that alcohol intake is related to risk of breast cancer and that intake of vegetables and fruits may reduce risk. Utilizing an existing case control study, we propose to examine two etiological mechanisms, one-carbon metabolism and/or oxidative stress and breast cancer. Our first aim is to examine the relation of elements related to one-carbon metabolism with risk. We propose a) to investigate genetic variation in enzymes important in one-carbon metabolism (methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MS) and cystathione B-synthase (CBS)) in relation to risk and to investigate interaction of these genetic factors with dietary folate and alcohol with breast cancer risk; b) to investigate the association of dietary folate and alcohol and these genetic factors with total p53 mutations and with particular p53 mutations and c) to investigate the association of dietary folate and alcohol and these genetic factors with hypermethylation of the p16 gene, the BRCA1 gene and the estrogen receptor gene in breast tumors. Our second aim is to examine elements related to oxidative stress and antioxidants with risk. We propose to a) examine the relation of genetic variation in an enzyme important in the control of oxidative balance (manganese superoxide dismutase (MnSOD)) and to examine interactions of this genetic factor with dietary factors both oxidants and antioxidants; and b) to investigate the association between dietary sources of oxidants and antioxidants with total and particular p53 mutations. By combining information on intake, genetic susceptibility and tumor characteristics, it will be possible to make clearer inferences about the role of these two mechanisms in breast cancer etiology, with potentially important public health implications.
Funding Period: 2002-06-01 - 2007-05-31
more information: NIH RePORT

Top Publications

  1. pmc Association of prediagnostic physical activity with survival following breast cancer diagnosis: influence of TP53 mutation status
    Meng Hua Tao
    Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, Box 1057, New York, NY, 10029, USA
    Cancer Causes Control 24:2177-86. 2013
  2. pmc The association of depressive symptoms and pulmonary function in healthy adults
    Heather M Ochs-Balcom
    Department of Social and Preventive Medicine, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214 8001
    Psychosom Med 75:737-43. 2013
  3. pmc Pregnancy-related characteristics and breast cancer risk
    Theodore M Brasky
    Division of Cancer Prevention and Control, The Ohio State University College of Medicine, Columbus, OH, USA
    Cancer Causes Control 24:1675-85. 2013
  4. pmc Dietary patterns related to glycemic index and load and risk of premenopausal and postmenopausal breast cancer in the Western New York Exposure and Breast Cancer Study
    Susan E McCann
    Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Am J Clin Nutr 86:465-71. 2007
  5. pmc BRCA1 polymorphisms and breast cancer epidemiology in the Western New York exposures and breast cancer (WEB) study
    Luisel J Ricks-Santi
    National Human Genome Center at Howard University, Washington, District of Columbia, USA
    Genet Epidemiol 37:504-11. 2013
  6. pmc Exposure to traffic emissions: associations with biomarkers of antioxidant status and oxidative damage
    Yanli Li
    Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY, USA
    Environ Res 121:31-8. 2013
  7. pmc Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype
    Theodore M Brasky
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
    Cancer Causes Control 22:965-75. 2011
  8. pmc Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study
    Michelle R Roberts
    Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY 14214, USA
    Carcinogenesis 32:1223-30. 2011
  9. pmc Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study
    Meng Hua Tao
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, NY, USA
    Am J Clin Nutr 94:831-8. 2011
  10. pmc Promoter methylation of E-cadherin, p16, and RAR-β(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism
    Meng Hua Tao
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York 14214, USA
    Nutr Cancer 63:1143-50. 2011

Scientific Experts

Detail Information

Publications23

  1. pmc Association of prediagnostic physical activity with survival following breast cancer diagnosis: influence of TP53 mutation status
    Meng Hua Tao
    Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, Box 1057, New York, NY, 10029, USA
    Cancer Causes Control 24:2177-86. 2013
    ..However, it is not clear whether this association differs by molecular features of the tumor or by recency of the physical activity to the time of diagnosis...
  2. pmc The association of depressive symptoms and pulmonary function in healthy adults
    Heather M Ochs-Balcom
    Department of Social and Preventive Medicine, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214 8001
    Psychosom Med 75:737-43. 2013
    ..We sought to add to the literature as to whether depression is associated with pulmonary function in healthy adults...
  3. pmc Pregnancy-related characteristics and breast cancer risk
    Theodore M Brasky
    Division of Cancer Prevention and Control, The Ohio State University College of Medicine, Columbus, OH, USA
    Cancer Causes Control 24:1675-85. 2013
    ..We observed strong inverse associations between pregnancy N&V and breast cancer risk. Replication of these findings and exploration of underlying mechanisms could provide important insight into breast cancer etiology and prevention...
  4. pmc Dietary patterns related to glycemic index and load and risk of premenopausal and postmenopausal breast cancer in the Western New York Exposure and Breast Cancer Study
    Susan E McCann
    Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Am J Clin Nutr 86:465-71. 2007
    ..Reduced rank regression (RRR) has been used to identify dietary patterns that predict variation in a selected risk factor and may be useful in describing dietary exposures associated with glycemic index (GI) and glycemic load (GL)...
  5. pmc BRCA1 polymorphisms and breast cancer epidemiology in the Western New York exposures and breast cancer (WEB) study
    Luisel J Ricks-Santi
    National Human Genome Center at Howard University, Washington, District of Columbia, USA
    Genet Epidemiol 37:504-11. 2013
    ..08-4.93). The BRCA1 variants studied may play a role in the etiology of triple negative breast cancer and may interact with environmental factors such as hormone therapy or smoking and increase sporadic breast cancer risk...
  6. pmc Exposure to traffic emissions: associations with biomarkers of antioxidant status and oxidative damage
    Yanli Li
    Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY, USA
    Environ Res 121:31-8. 2013
    ....
  7. pmc Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype
    Theodore M Brasky
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
    Cancer Causes Control 22:965-75. 2011
    ..28, 95% CI: 1.04-1.57), as well as luminal A or B breast cancers. These findings support the hypothesis of heterogeneous etiologies of breast cancer subtypes and that aspirin and ibuprofen vary in their effects...
  8. pmc Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study
    Michelle R Roberts
    Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY 14214, USA
    Carcinogenesis 32:1223-30. 2011
    ..These results indicate that some of the variants in BER and NER genes may influence risk of postmenopausal breast cancer...
  9. pmc Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study
    Meng Hua Tao
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, NY, USA
    Am J Clin Nutr 94:831-8. 2011
    ..The mechanism of the observed association between body mass, particularly centralized body fat, and postmenopausal breast cancer risk is not well understood...
  10. pmc Promoter methylation of E-cadherin, p16, and RAR-β(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism
    Meng Hua Tao
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York 14214, USA
    Nutr Cancer 63:1143-50. 2011
    ..This finding, however, does not exclude the possibility that intake of such nutrients might have the ability to modulate promoter methylation in normal or premalignant (dysplastic) breast tissue...
  11. pmc Use of nonsteroidal anti-inflammatory drugs and survival following breast cancer diagnosis
    Yanli Li
    Department of Social and Preventive Medicine, State University of New York at Buffalo, 265 Farber Hall, Buffalo, NY 14214, USA
    Cancer Epidemiol Biomarkers Prev 21:239-42. 2012
    ..While there is accumulating evidence that use of nonsteroidal anti-inflammatory drugs (NSAID) decreases breast cancer risk, little is known about the impact of NSAIDs on survival after breast cancer diagnosis...
  12. pmc Alcohol consumption in relation to aberrant DNA methylation in breast tumors
    Meng Hua Tao
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
    Alcohol 45:689-99. 2011
    ....
  13. pmc Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes
    Heather M Ochs-Balcom
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
    Am J Clin Nutr 93:5-10. 2011
    ..Emerging data suggest a role for the vitamin D receptor (VDR) in lipogenesis and adipocyte differentiation...
  14. pmc Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study
    Theodore M Brasky
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
    Breast Cancer Res Treat 126:157-65. 2011
    ..Better understanding of the role of COX-2 genetic variation and interaction with NSAID use in breast carcinogenesis has potential to inform prevention strategies...
  15. pmc DNA methylation in endometrial cancer
    Meng Hua Tao
    Department of Social and Preventive Medicine School of Public Health and Health Professions University at Buffalo, NY, USA
    Epigenetics 5:491-8. 2010
    ....
  16. pmc Non-steroidal anti-inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study
    Theodore M Brasky
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, USA
    Cancer Causes Control 21:1503-12. 2010
    ..Results of studies of non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer have been inconsistent. Timing of exposure and analysis of individual NSAIDs should be considered...
  17. pmc Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study
    Susan E McCann
    Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Breast Cancer Res Treat 122:229-35. 2010
    ..In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer...
  18. ncbi Perinatal exposures and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study
    Maddalena Barba
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
    Cancer Causes Control 17:395-401. 2006
    ..There is increasing evidence that early life exposures, such as birth weight, infant feeding practices, birth rank and maternal age at delivery may play a role in breast carcinogenesis...
  19. ncbi Exposure to traffic emissions throughout life and risk of breast cancer: the Western New York Exposures and Breast Cancer (WEB) study
    Jing Nie
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, 270 Farber Hall, University at Buffalo, 3435 Main St, Buffalo, NY 14214, USA
    Cancer Causes Control 18:947-55. 2007
    ..In this study, we examined breast cancer risk in relation to exposure to air pollution from traffic emissions throughout life...
  20. ncbi Effect modification by catalase genotype suggests a role for oxidative stress in the association of hormone replacement therapy with postmenopausal breast cancer risk
    Sylvia K Quick
    Department of Social, State University of New York at Buffalo, Buffalo, NY, USA
    Cancer Epidemiol Biomarkers Prev 17:1082-7. 2008
    ..50-3.59). Increased risk was limited to estrogen receptor-positive tumors. Our findings suggest that CAT genotype modifies the effect of HRT use on breast cancer risk and that HRT may affect risk by affecting oxidative stress...
  21. pmc DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR
    Meng Hua Tao
    Department of Social and Preventive Medicine, School of Public Health and Health Professions, 270 Farber Hall, University at Buffalo, Buffalo, NY 14214, USA
    Cancer Epidemiol Biomarkers Prev 18:998-1002. 2009
    ..Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-beta2 genes in breast cancer...
  22. pmc Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk
    Mary E Platek
    Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA
    Cancer Epidemiol Biomarkers Prev 18:2453-9. 2009
    ..80; 95% CI, 1.03-3.28) compared with nondrinkers who were homozygote CC. Our findings indicate that among postmenopausal women, increased breast cancer risk with alcohol consumption may be as a result of effects on one-carbon metabolism...
  23. ncbi p53 Mutation analysis in breast tumors by a DNA microarray method
    Meredith Tennis
    Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 1465, USA
    Cancer Epidemiol Biomarkers Prev 15:80-5. 2006
    ..We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study...