Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women.
Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women.
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DOI：
10.1007/s10549-013-2690-z
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发表时间：
2013-09
影响因子：
3.8
通讯作者：
Slattery, Martha L.
中科院分区：
文献类型：
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作者：
Boone, Stephanie D.;Baumgartner, Kathy B.;Baumgartner, Richard N.;Connor, Avonne E.;Pinkston, Christina M.;John, Esther M.;Hines, Lisa M.;Stern, Mariana C.;Giuliano, Anna R.;Torres-Mejia, Gabriela;Brock, Guy N.;Groves, Frank D.;Kerber, Richard A.;Wolff, Roger K.;Slattery, Martha L.
关键词：
TGF-β信号通路通过调节各种细胞过程在乳腺癌的发生和促进中发挥重要作用。我们通过乳腺癌健康差异研究评估了八个基因（TGF-β1、TGF-β2、TGF-βR1、TGF-βR2、TGF-βR3、RUNX1、RUNX2 和 RUNX3）的遗传变异是否与女性患乳腺癌的风险相关。分析共纳入 3,524 例病例（1,431 例非西班牙裔白人 (NHW)；2,093 例西班牙裔/美洲原住民 (NA)）和 4,209 例人群对照（1,599 例 NHW；2,610 例西班牙裔/美洲原住民）。确定了 47 个单核苷酸多态性 (SNP) 的基因型。此外，104 个祖先信息标记估计了 NA 祖先的比例。评估了绝经状态、NA 血统和雌激素受体 (ER)/孕激素受体肿瘤表型与乳腺癌总体风险的关联。经过多重比较调整后，两个 SNP 与乳腺癌风险显着相关：RUNX3 (rs906296 ORCG/GG = 1.15 95 % CI 1.04–1.26) 和 TGF-β1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81–0.98)。 RUNX3 (rs906296) 和 TGF-βR2 (rs3773644) 与绝经前女性（padj 分别为 0.002 和 0.02）以及具有中至高 NA 血统的女性（padj 分别为 0.04 和 0.01）的风险相关。自我报告的种族与 NA 血统密切相关 (r = 0.86)。 NA 血统和 RUNX1 (rs7279383, padj = 0.04) 之间存在显着的相互作用。四个 RUNX SNP 与 ER 肿瘤风险增加相关。结果证明 TGF-β 和 RUNX 基因的遗传变异与乳腺癌风险相关。这是第一份关于 NA 血统女性中 TGF-β 和 RUNX 基因的遗传变异与乳腺癌风险之间存在显着关联的报告。
The TGF-β signaling pathway has a significant role in breast cancer initiation and promotion by regulating various cellular processes. We evaluated whether genetic variation in eight genes (TGF-β1, TGF-β2, TGF-βR1, TGF-βR2, TGF-βR3, RUNX1, RUNX2, and RUNX3) is associated with breast cancer risk in women from the Breast Cancer Health Disparities Study. A total of 3,524 cases (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209 population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were determined. Additionally, 104 ancestral informative markers estimated proportion of NA ancestry. Associations with breast cancer risk overall, by menopausal status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor phenotype were evaluated. After adjustment for multiple comparisons, two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG = 1.15 95 % CI 1.04–1.26) and TGF-β1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81–0.98). RUNX3 (rs906296) and TGF-βR2 (rs3773644) were associated with risk in pre-menopausal women (padj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (padj = 0.04 and 0.01, respectively). Self-reported race was strongly correlated with NA ancestry (r = 0.86). There was a significant interaction between NA ancestry and RUNX1 (rs7279383, padj = 0.04). Four RUNX SNPs were associated with increased risk of ER-tumors. Results provide evidence that genetic variation in TGF-β and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-β and RUNX genes and breast cancer risk among women of NA ancestry.
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影响因子：
--
作者：
Bursac, Zoran;Gauss, C Heath;Williams, David Keith;Hosmer, David W
通讯作者：
Hosmer, David W
影响因子：
3.8
作者：
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Hunter DJ
影响因子：
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作者：
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Yanagisawa, Junn
影响因子：
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作者：
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通讯作者：
Neil, JC
影响因子：
5.3
作者：
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通讯作者：
Seldin, MF