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Maternal nutrition and breast cancer fetal programming: influence of nutrient-epigenome interactions in early life

Grant number: 11/23259-4
Support type:Regular Research Grants
Duration: September 01, 2012 - August 31, 2014
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal researcher:Thomas Prates Ong
Grantee:Thomas Prates Ong
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Breast cancer is a major public health problem. One intriguing hypothesis that has not gained much attention in the literature, despite its biological plausibility, is that cancer, including breast cancer, has a fetal origin. Although the fetal hypothesis has been investigated mainly in the context of other non-communicable diseases including cardiovascular disease, obesity and type II diabetes, epidemiological and experimental evidence show that in utero exposures to toxicants, hormones and nutritional factors could disrupt the fetal environment and alter mammary gland development and thus programme breast cancer risk in adult life. Nutritional modulation of the epigenome could be associated with this phenomenon. Therefore, the aim of this project is to investigate the impact of maternal overnutrition, represented by a high-saturated fatty-acid diet, during gestational phase, on fetal programming of breast cancer and implications of potential nutrient-epigenome interactions. For that a rat experiment will be conducted in which pregnant dams will be fed such hyperlipidic diet. Alterations in morphology, global and gene-specific epigenetic (DNA methylation and histone modifications) marks, global gene expression and expression of genes associated to cell proliferation and epigenetic processes, as well as neoplastic development, will be evaluated in the female offspring's mammary glands. Results may lead to identification of breast cancer nutritional aetiological factor operating in early life and associated epigenetic mechanisms. They may also assist in the definition of novel nutritional breast cancer risk reduction strategies that consider early life as a window of opportunity and the epigenome as promising molecular target for intervention. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANDRADE, FABIA DE OLIVEIRA; FONTELLES, CAMILE CASTILHO; ROSIM, MARIANA PAPALEO; DE OLIVEIRA, TIAGO FRANCO; DE MELO LOUREIRO, ANA PAULA; MANCINI-FILHO, JORGE; ROGERO, MARCELO MACEDO; MORENO, FERNANDO SALVADOR; DE ASSIS, SONIA; BARBISAN, LUIZ FERNANDO; et al. Exposure to lard-based high-fat diet during fetal and lactation periods modifies breast cancer susceptibility in adulthood in rats. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 25, n. 6, p. 613-622, . (10/11742-0, 11/23259-4, 12/03330-9)
ANDRADE, FABIA DE OLIVEIRA; DE ASSIS, SONIA; JIN, LU; FONTELLES, CAMILE CASTILHO; BARBISAN, LUIS FERNANDO; PURGATTO, EDUARDO; HILAKIVI-CLARKE, LEENA; ONG, THOMAS PRATES. Lipidomic fatty acid profile and global gene expression pattern in mammary gland of rats that were exposed to lard-based high fat diet during fetal and lactation periods associated to breast cancer risk in adulthood. Chemico-Biological Interactions, v. 239, p. 118-128, . (10/11742-0, 11/23259-4, 12/03330-9)
DA CRUZ, RAQUEL SANTANA; ANDRADE, FABIA DE OLIVEIRA; DE OCA CARIONI, VIVIAN MONTES; ROSIM, MARIANA PAPALEO; PAULINO MIRANDA, MAYARA LILIAN; FONTELLES, CAMILE CASTILHO; DE OLIVEIRA, PEDRO VITORIANO; BARBISAN, LUIS FERNANDO; CASTRO, INAR ALVES; ONG, THOMAS PRATES. Dietary zinc deficiency or supplementation during gestation increases breast cancer susceptibility in adult female mice offspring following a J-shaped pattern and through distinct mechanisms. Food and Chemical Toxicology, v. 134, . (13/07914-8, 11/23259-4, 13/04960-9)
FONTELLES, CAMILE CASTILHO; GUIDO, LUIZA NICOLOSI; ROSIM, MARIANA PAPALEO; ANDRADE, FABIA DE OLIVEIRA; JIN, LU; INCHAUSPE, JESSICA; PIRES, VANESSA CARDOSO; DE CASTRO, INAR ALVES; HILAKIVI-CLARKE, LEENA; DE ASSIS, SONIA; et al. Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets. BREAST CANCER RESEARCH, v. 18, . (11/23259-4)
GUIDO, LUIZA N.; FONTELLES, CAMILE C.; ROSIM, MARIANA P.; PIRES, VANESSA C.; COZZOLINO, SILVIA M. F.; CASTRO, INAR A.; BOLANOS-JIMENEZ, FRANCISCO; BARBISAN, LUIS F.; ONG, THOMAS P.. Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring. International Journal of Cancer, v. 139, n. 8, p. 1873-1882, . (11/23259-4)

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