Dataset Information

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.

SUBMITTER: Slattery ML

PROVIDER: S-EPMC3152602 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States.

Slattery Martha L ML Baumgartner Kathy B KB Giuliano Anna R AR Byers Tim T Herrick Jennifer S JS Wolff Roger K RK

Breast cancer research and treatment 20110408 2

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 ...[more]

PMID: 21475998

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Project description:Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 106) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10-8) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10-8) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10-8) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10-7) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.

Dataset Information

Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States.

Publications

Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States.

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