title: Paternal overweight is associated with increased breast cancer risk in daughters in a mouse model.
abstract: While many studies have shown that maternal weight and nutrition in pregnancy affects offspring's breast cancer risk, no studies have investigated the impact of paternal body weight on daughters' risk of this disease. Here, we show that diet-induced paternal overweight around the time of conception can epigenetically reprogram father's germ-line and modulate their daughters' birth weight and likelihood of developing breast cancer, using a mouse model. Increased body weight was associated with changes in the miRNA expression profile in paternal sperm. Daughters of overweight fathers had higher rates of carcinogen-induced mammary tumors which were associated with delayed mammary gland development and alterations in mammary miRNA expression. The hypoxia signaling pathway, targeted by miRNAs down-regulated in daughters of overweight fathers, was activated in their mammary tissues and tumors. This study provides evidence that paternal peri-conceptional body weight may affect daughters' mammary development and breast cancer risk and warrants further studies in other animal models and humans.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.|Departament of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo and Food Research Center, São Paulo, SP, Brazil.
authors.forename: Camile Castilho
authors.initials: CC
authors.lastname: Fontelles
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Elissa
authors.initials: E
authors.lastname: Carney
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Johan
authors.initials: J
authors.lastname: Clarke
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Nguyen M
authors.initials: NM
authors.lastname: Nguyen
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: M Idalia
authors.initials: MI
authors.lastname: Cruz
authors.affiliation: Departament of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo and Food Research Center, São Paulo, SP, Brazil.
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Hilakivi-Clarke
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: de Assis
mesh_terms: D000818:Animals; D001724:Birth Weight / Q000235:genetics; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004032:Diet / Q000379:methods; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005220:Fathers; D005260:Female; D008297:Male; D008321:Mammary Glands, Animal / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D009679:Nuclear Family; D050177:Overweight / Q000150:complications* / Q000473:pathology; D010287:Parent-Child Relations; D011247:Pregnancy; D012306:Risk
chemical_list: D035683:MicroRNAs