title: Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States.
abstract: Genome-wide association studies (GWAS) have identified several loci as being associated with breast cancer in mostly European populations. We focus on TNRC9 rs3803662, FGFR2 rs1219648 and rs2981582, MAP3K1 rs889312, and 2q35 rs13387042, to replicate in the 4-Corner's Breast Cancer Study of Hispanic (N = 565 cases and 714 controls) and non-Hispanic white (NHW) women (N = 1177 cases and 1330 controls). We evaluate associations by ethnicity, menopausal status, and tumor ER/PR status after adjusting for genetic admixture. TNRC9 AA genotype was associated with significant increased risk among NHW women (OR 1.54, 95% CI 1.14, 2.08; P trend 0.003). Both polymorphisms of FGFR2 were associated with statistically significant increased risk for NHW and Hispanic women; MAP3K1 was not associated with risk among either ethnic group. The polymorphism on 2q35 was associated with a statistically significant increased risk among Hispanic women (OR 1.53, 95% CI 1.08, 2.15 for the AA genotype; P trend = 0.004). Associations were significantly different among pre/peri-menopausal women for TNRC9 (P heterogeneity 0.008) and for 2q35 (P heterogeneity 0.08) for NHW and Hispanic women. Both FGFR2 polymorphisms reduced risk of ER-/PR- tumors in the presence of the minor allele among NHW women. Among Hispanic women, polymorphisms of the FGFR2 gene were associated with almost a twofold increase risk of an ER+/PR+ tumor, while non-significantly inversely associated with ER-/PR- tumors. Our data replicated some of the previously reported GWAS findings. Differences in associations were detected for NHW and Hispanic women by menopausal status and by ER/PR status of tumors.
authors.affiliation: University of Utah, Salt Lake City, UT, 84108, USA. marty.slattery@hsc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Kathy B
authors.initials: KB
authors.lastname: Baumgartner
authors.forename: Anna R
authors.initials: AR
authors.lastname: Giuliano
authors.forename: Tim
authors.initials: T
authors.lastname: Byers
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Herrick
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000367:Age Factors; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics*; D008593:Menopause / Q000208:ethnology / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D015206:Southwestern United States; D015534:Trans-Activators; D044465:White People / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human