Document Detail


High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring.
MedLine Citation:
PMID:  22968699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maternal exposures to environmental factors during pregnancy influence the risk of many chronic adult-onset diseases in the offspring. Here we investigate whether feeding pregnant rats a high-fat (HF)- or ethinyl-oestradiol (EE2)-supplemented diet affects carcinogen-induced mammary cancer risk in daughters, granddaughters and great-granddaughters. We show that mammary tumourigenesis is higher in daughters and granddaughters of HF rat dams and in daughters and great-granddaughters of EE2 rat dams. Outcross experiments suggest that the increase in mammary cancer risk is transmitted to HF granddaughters equally through the female or male germ lines, but it is only transmitted to EE2 granddaughters through the female germ line. The effects of maternal EE2 exposure on offspring's mammary cancer risk are associated with changes in the DNA methylation machinery and methylation patterns in mammary tissue of all three EE2 generations. We conclude that dietary and oestrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic means.
Authors:
Sonia de Assis; Anni Warri; M Idalia Cruz; Olusola Laja; Ye Tian; Bai Zhang; Yue Wang; Tim Hui-Ming Huang; Leena Hilakivi-Clarke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature communications     Volume:  3     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2012  
Date Detail:
Created Date:  2012-09-12     Completed Date:  2013-02-01     Revised Date:  2013-04-12    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1053     Citation Subset:  IM    
Affiliation:
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, The Research Building, Room E407, Washington, District of Columbia 20057, USA. deassiss@georgetown.edu
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE40251
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MeSH Terms
Descriptor/Qualifier:
Animals
Dietary Fats / adverse effects*
Ethinyl Estradiol / adverse effects*
Female
Mammary Glands, Animal / pathology
Mammary Neoplasms, Animal / chemically induced*,  etiology*
Maternal Exposure / adverse effects*
Pregnancy
Prenatal Exposure Delayed Effects
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
CA160036/CA/NCI NIH HHS; P30CA051668/CA/NCI NIH HHS; P30CA054174/CA/NCI NIH HHS; R01CA069065/CA/NCI NIH HHS; R01ES017594/ES/NIEHS NIH HHS; R03 CA150040/CA/NCI NIH HHS; R03CA150040/CA/NCI NIH HHS; R21GM085665/GM/NIGMS NIH HHS; U54 CA100970/CA/NCI NIH HHS; U54 CA149147/CA/NCI NIH HHS; U54CA100970/CA/NCI NIH HHS; U54CA113001/CA/NCI NIH HHS; U54CA149147/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Dietary Fats; 57-63-6/Ethinyl Estradiol
Comments/Corrections

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