title: High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring.
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.
authors.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
authors.forename: Sonia
authors.initials: S
authors.lastname: de Assis
authors.forename: Anni
authors.initials: A
authors.lastname: Warri
authors.forename: M Idalia
authors.initials: MI
authors.lastname: Cruz
authors.forename: Olusola
authors.initials: O
authors.lastname: Laja
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Bai
authors.initials: B
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Tim Hui-Ming
authors.initials: TH
authors.lastname: Huang
authors.forename: Leena
authors.initials: L
authors.lastname: Hilakivi-Clarke
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005260:Female; D008321:Mammary Glands, Animal / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000209:etiology*; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D004997:Ethinyl Estradiol