title: Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study.
abstract: BACKGROUND
  Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship.
  
  
  METHODS
  We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women.
  
  
  RESULTS
  Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size. There were no significant associations with breast cancer risk between genes and SNPs overall. However, LEPR was significantly associated with breast cancer risk among women with low IA ancestry (PARTP=0.024); POMC was significantly associated with breast cancer risk among women with intermediate (PARTP=0.015) and high (PARTP=0.012) IA ancestry. The overall pathway was statistically significant for pre-menopausal women with low IA ancestry (PARTP=0.05), as was cocaine and amphetamine regulated transcript protein (CARTPT) (PARTP=0.014) and ghrelin (GHRL) (PARTP=0.007). POMC was significantly associated with breast cancer risk among post-menopausal women with higher IA ancestry (PARTP=0.005). Three SNPs in LEPR (rs6704167, rs17412175, and rs7626141), and adiponectin (ADIPOQ); rs822391) showed significant 4-way interactions (GxExMenopausexAncestry) for multiple indicators of body size among pre-menopausal women.
  
  
  CONCLUSIONS
  Energy homeostasis genes were associated with breast cancer risk; menopausal status, body size, and genetic ancestry influenced this relationship.
authors.affiliation: University of Utah, Department of Medicine, 383 Colorow, Salt Lake City, UT 84108, United States. Electronic address: marty.slattery@hsc.utah.edu.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: University of Utah, Department of Medicine, 383 Colorow, Salt Lake City, UT 84108, United States.
authors.forename: Abbie
authors.initials: A
authors.lastname: Lundgreen
authors.affiliation: Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, CO 80918, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hines
authors.affiliation: University of Utah, Department of Medicine, 383 Colorow, Salt Lake City, UT 84108, United States.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.affiliation: Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Av. Universidad No. 655, Col. Sta. Ma. Ahuacatitlán, Cuernavaca, Morelos CP 62,100, Mexico.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Torres-Mejia
authors.affiliation: Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40292, United States.
authors.forename: Kathy N
authors.initials: KN
authors.lastname: Baumgartner
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA 94538, United States; Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, United States.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
mesh_terms: D000328:Adult; D000368:Aged; D049628:Body Size / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008593:Menopause / Q000502:physiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics
keywords: Breast cancer; Disparities; Energy homeostasis