Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women

Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner, Avonne Connor, Christina M. Pinkston, Esther M. John, Lisa M. Hines, Mariana C. Stern, Anna R. Giuliano, Gabriela Torres-Mejia, Guy N. Brock, Frank D. Groves, Richard A. Kerber, Roger K. Wolff, Martha L. Slattery

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)287-297
Number of pages11
JournalBreast Cancer Research and Treatment
Volume141
Issue number2
DOIs
StatePublished - Sep 2013
Externally publishedYes

Fingerprint

North American Indians
Hispanic Americans
Breast Neoplasms
Single Nucleotide Polymorphism
Estrogen Receptors
Genes
Population Control
Progesterone Receptors
Neoplasms
Genotype
Phenotype
Health

Keywords

  • Breast Cancer Health Disparities Study
  • Breast cancer risk
  • Hispanic
  • Native American ancestry
  • Non-Hispanic white
  • TGF-β signaling pathway

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women. / Boone, Stephanie D.; Baumgartner, Kathy B.; Baumgartner, Richard N.; Connor, Avonne; 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.

In: Breast Cancer Research and Treatment, Vol. 141, No. 2, 09.2013, p. 287-297.

Research output: Contribution to journalArticle

Boone, SD, Baumgartner, KB, Baumgartner, RN, Connor, A, Pinkston, CM, John, EM, Hines, LM, Stern, MC, Giuliano, AR, Torres-Mejia, G, Brock, GN, Groves, FD, Kerber, RA, Wolff, RK & Slattery, ML 2013, 'Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women', Breast Cancer Research and Treatment, vol. 141, no. 2, pp. 287-297. https://doi.org/10.1007/s10549-013-2690-z
Boone, Stephanie D. ; Baumgartner, Kathy B. ; Baumgartner, Richard N. ; Connor, Avonne ; 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. / Associations between genetic variants in the TGF-β signaling pathway and breast cancer risk among Hispanic and non-Hispanic white women. In: Breast Cancer Research and Treatment. 2013 ; Vol. 141, No. 2. pp. 287-297.
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