title: FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women.
abstract: Twenty-nine single-nucleotide polymorphisms (SNPs) from previously published genome-wide association studies (GWAS) and multiple ancestry informative markers were genotyped in the Carolina Breast Cancer Study (CBCS) (742 African-American (AA) cases, 1230 White cases; 658 AA controls, 1118 White controls). In the entire study population, 9/10 SNPs in fibroblast growth factor receptor 2 (FGFR2) were significantly associated with breast cancer after adjusting for age, race and European ancestry [odds ratios (OR) range 1.17-1.81]. Associations were observed for SNPs in FGFR2, LSP1, H19, TLR1/TLR6 and RELN for AA; FGFR2, TNRC9, H19 and MAP3K1 for Whites; FGFR2, TNRC9, Msc5A1 and chromosome 8q for women > or =50 years old and FGFR2 and TNRC9 for women <50 years old. FGFR2 haplotypes based upon rs11200014, rs2981579, rs1219648 and rs2420946 were associated with increased risk of breast cancer, including the GTGT haplotype in AAs [OR = 1.27, 95% confidence interval (CI) 1.04-1.56] and younger women of either race [OR = 1.35, 95% CI 1.02-1.78) and the ATGT haplotype in Whites (OR = 1.30, 95% CI 1.15-1.46). Recent GWAS hits for breast cancer in Europeans and Whites (i.e. women of European descent) thus showed evidence of replication among AAs and Whites in the CBCS. Several new haplotypes were associated with breast cancer in AA and younger women, particularly the FGFR2 GTGT haplotype. These results highlight the need to conduct GWAS among younger women and in a variety of racial-ethnic populations.
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106-5065, USA. jsb42@case.edu
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.forename: Priya B
authors.initials: PB
authors.lastname: Shetty
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Guan
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nyante
authors.forename: Jingchun
authors.initials: J
authors.lastname: Luo
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Brennan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics; D016001:Confidence Intervals; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005799:Genes, Dominant; D055106:Genome-Wide Association Study; D006801:Humans; D056892:Mediator Complex / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D000091042:Reelin Protein; D055815:Young Adult; D001741:Black or African American
chemical_list: D004273:DNA, Neoplasm; D056892:Mediator Complex; D000091042:Reelin Protein; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; C000717127:RELN protein, human; C505530:CASP8 protein, human; D053181:Caspase 8