title: Evaluating genome-wide association study-identified breast cancer risk variants in African-American women.
abstract: Genome-wide association studies (GWAS), conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls), recruited in the Southern Community Cohort Study (SCCS) and the Nashville Breast Health Study (NBHS). Seven SNPs were statistically significant (P ≤ 0.05) with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT), rs999737 (14q24/RAD51L1), rs13387042 (2q35/TNP1), rs1219648 (10q26/FGFR2), rs8170 (19p13/BABAM1), rs17817449 (16q12/FTO), and rs13329835 (16q23/DYL2). A marginally significant association (P<0.10) was found for three additional SNPs: rs1045485 (2q33/CASP8), rs4849887 (2q14/INHBB), and rs4808801 (19p13/ELL). Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B), rs941764 (14q32/CCDC88C), and rs17529111 (6q14/FAM46A), showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference), to 1.75 (1.30-2.37), 1.56 (1.15-2.11), 2.02 (1.50-2.74) and 2.63 (1.96-3.52), respectively, (P = 7.8 × 10(-10)). Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. Jirong.Long@Vanderbilt.Edu
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Signorello
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Sandra
authors.initials: S
authors.lastname: Deming-Halverson
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
authors.forename: Maureen
authors.initials: M
authors.lastname: Sanderson
authors.forename: Joe
authors.initials: J
authors.lastname: Dennis
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Michailidou
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Michailiou
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: William J
authors.initials: WJ
authors.lastname: Blot
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology* / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide