title: Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.
abstract: The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P=9 × 10(-18)), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21-0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49-0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations.
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Fejerman
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, California 94122, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Ahmadiyeh
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: University of Minnesota Genomics Center, Minneapolis, Minnesota 55455, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Beckman
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Caswell
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, California 94122, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Tsung
authors.affiliation: 1] Cancer Prevention Institute of California, Fremont, California 94538, USA [2] Division of Epidemiology, Department of Health Research and Policy, Stanford Cancer Institute, Stanford University School of Medicine, Palo Alto, California 94305, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.affiliation: National Institute of Public Health, Cuernavaca 62100, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Torres-Mejia
authors.affiliation: 1] Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California 95616, USA [2] Research Group, Citogenética Filogenia y Evolución de Poblaciones, University of Tolima, Ibagué 7652000, Colombia.
authors.forename: Luis
authors.initials: L
authors.lastname: Carvajal-Carmona
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California 95616, USA.
authors.forename: María Magdalena
authors.initials: MM
authors.lastname: Echeverry
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California 95616, USA.
authors.forename: Anna Marie D
authors.initials: AM
authors.lastname: Tuazon
authors.affiliation: Research Group, Citogenética Filogenia y Evolución de Poblaciones, University of Tolima, Ibagué 7652000, Colombia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ramirez
authors.affiliation: Department of Genetics, Stanford University, Palo Alto, California 94305, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gignoux
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Institute for Human Genetics, University of California San Francisco, San Francisco, California 94158, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, Institute for Human Genetics, University of California San Francisco, San Francisco, California 94158, USA.
authors.forename: Esteban
authors.initials: E
authors.lastname: Gonzalez-Burchard
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.affiliation: Department of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Ilir
authors.initials: I
authors.lastname: Agalliu
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
authors.forename: Eliseo J
authors.initials: EJ
authors.lastname: Perez-Stable
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, University of California San Fancisco, San Francisco, California 94158, USA.
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008327:Mammography; D008800:Mexico; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen