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High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring

Author

Listed:
  • Sonia de Assis

    (Lombardi Comprehensive Cancer Center, Georgetown University)

  • Anni Warri

    (Lombardi Comprehensive Cancer Center, Georgetown University
    Institute of Biomedicine, University of Turku Medical Faculty)

  • M. Idalia Cruz

    (Lombardi Comprehensive Cancer Center, Georgetown University)

  • Olusola Laja

    (Lombardi Comprehensive Cancer Center, Georgetown University)

  • Ye Tian

    (Virginia Tech)

  • Bai Zhang

    (Virginia Tech
    Johns Hopkins Medical Institutions)

  • Yue Wang

    (Virginia Tech)

  • Tim Hui-Ming Huang

    (Institute of Biotechnology and Cancer Therapy and Research Center, University of Texas Health Science Center)

  • Leena Hilakivi-Clarke

    (Lombardi Comprehensive Cancer Center, Georgetown University)

Abstract

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.

Suggested Citation

  • Sonia de Assis & Anni Warri & M. Idalia Cruz & Olusola Laja & Ye Tian & Bai Zhang & Yue Wang & Tim Hui-Ming Huang & Leena Hilakivi-Clarke, 2012. "High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2058
    DOI: 10.1038/ncomms2058
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