title: Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans.
abstract: Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and replicated associations (P < 0.05) with only 4 variants. Through fine-mapping, we identified markers in four regions that better capture the association with breast cancer risk in African Americans as defined by the index signal (2q35, 5q11, 10q26 and 19p13). We also identified statistically significant associations with markers in four separate regions (8q24, 10q22, 11q13 and 16q12) that are independent of the index signals and may represent putative novel risk variants. In aggregate, the more informative markers found in the study enhance the association of these risk regions with breast cancer in African Americans [per allele odds ratio (OR) = 1.18, P = 2.8 × 10(-24) versus OR = 1.04, P = 6.1 × 10(-5)]. In this detailed analysis of the known breast cancer risk loci, we have validated and improved upon markers of risk that better characterize their association with breast cancer in women of African ancestry.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Gary K
authors.initials: GK
authors.lastname: Chen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Deming
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.forename: Sarah
authors.initials: S
authors.lastname: Nyante
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Sue A
authors.initials: SA
authors.lastname: Ingles
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Rodriguez-Gil
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D055815:Young Adult