title: Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.
abstract: BACKGROUND
  Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population.
  
  
  METHODS
  We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions.
  
  
  RESULTS
  We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, <12 months, and >12 months breastfeeding, respectively, Pinteraction 0.014].
  
  
  CONCLUSIONS
  The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women.
  
  
  CONCLUSIONS
  These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk.
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California. laura.fejerman@ucsf.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Fejerman
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, California.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.affiliation: Cancer Prevention Institute of California, Fremont, California and Department of Health Research and Policy (Epidemiology), and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.affiliation: Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Cuernavaca, Morelos, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Torres-Mejía
authors.affiliation: Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, Colorado.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hines
authors.affiliation: Department of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.affiliation: Department of Epidemiology and Population Health, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
authors.forename: Kathy B
authors.initials: KB
authors.lastname: Baumgartner
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Giuliano
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California.
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California.
authors.forename: Eliseo J
authors.initials: EJ
authors.lastname: Pérez-Stable
authors.affiliation: Department of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000208:ethnology* / Q000209:etiology / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000208:ethnology* / Q000235:genetics; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics* / Q000706:statistics & numerical data; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008019:Life Style / Q000208:ethnology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors