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

• Other Authors: 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.
• Language: unknown
• Subjects: Article; reast cancer risk; Breast Cancer Health Disparities Study; TGF-β; signaling pathway; Native American ancestry; Hispanic; Non-Hispanic white; Adult; Aged; 80 and over; Alleles; Breast Neoplasms; Case-Control Studies; European Continental Ancestry Group; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Hispanic Americans; Humans; Menopause; Middle Aged; Polymorphism; Single Nucleotide; Receptors; Estrogen; Progesterone; Risk; Signal Transduction; Southwestern United States; Transforming Growth Factor beta; Young Adult; Orca
• Online Access: http://stacks.cdc.gov/view/cdc/30028/

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 (p adj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (p adj = 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, p adj = 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. 1U58 DP000807-01/DP/NCCDPHP CDC HHS/United States CA078552/CA/NCI NIH HHS/United States CA078682/CA/NCI NIH HHS/United States CA078762/CA/NCI NIH HHS/United States CA078802/CA/NCI NIH HHS/United States CA14002/CA/NCI NIH HHS/United States CA63446/CA/NCI NIH HHS/United States CA77305/CA/NCI NIH HHS/United States HHSN261201000036C/PHS HHS/United States N01-PC-67000/PC/NCI NIH HHS/United States R01 CA063446/CA/NCI NIH HHS/United States R01 CA078552/CA/NCI NIH HHS/United States R01 CA078682/CA/NCI NIH HHS/United States R01 CA078762/CA/NCI NIH HHS/United States R01 CA078802/CA/NCI NIH HHS/United States R01 CA140002/CA/NCI NIH HHS/United States 2014-09-14T00:00:00Z 24036662 PMC4088254