The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study

Details

• Alternative Title:
  Cancer Causes Control
• Personal Author:
  Slattery, Martha L. ; Lundgreen, Abbie ; Stern, Marianna C. ; Hines, Lisa ; Wolff, Roger K. ; Giuliano, Anna R. ; Baumgartner, Kathy B. ; John, Esther M.
• Description:
  The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity. The Breast Cancer Health Disparities Study includes participants from the 4-Corners Breast Cancer Study (n = 1,391 cases) and the San Francisco Bay Area Breast Cancer Study (n = 946 cases) who have been followed for survival. We evaluated 28 genes in the TGF-β signaling pathway using a tagSNP approach. Adaptive rank truncated product (ARTP) was used to test the gene and pathway significance by Native American (NA) ancestry and by self-reported ethnicity (non-Hispanic white (NHW) and Hispanic/NA). Genetic variation in the TGF-β signaling pathway was associated with overall breast cancer survival (P ARTP = 0.05), especially for women with low NA ancestry (P ARTP = 0.007) and NHW women (P ARTP = 0.006). BMP2, BMP4, RUNX1, and TGFBR3 were significantly associated with breast cancer survival overall (P ARTP = 0.04, 0.02, 0.002, and 0.04, respectively). Among women with low NA, ancestry associations were as follows: BMP4 (P ARTP = 0.007), BMP6 (P ARTP = 0.001), GDF10 (P ARTP = 0.05), RUNX1 (P ARTP = 0.002), SMAD1 (P ARTP = 0.05), and TGFBR2 (P ARTP = 0.02). A polygenic risk model showed that women with low NA ancestry and high numbers of at-risk alleles had twice the risk of dying from breast cancer as did women with high NA ancestry. Our data suggest that genetic variation in the TGF-β signaling pathway influences breast cancer survival. Associations were similar when the analyses were stratified by genetic ancestry or by self-reported ethnicity.
• Subjects:
  Adult Aged Breast Neoplasms Case-Control Studies DNA, Neoplasm Female Genetic Predisposition To Disease Healthcare Disparities Hispanic Or Latino Humans Middle Aged Polymorphism, Single Nucleotide San Francisco Signal Transduction Survival Analysis Transforming Growth Factor Beta White People

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• Source:
  Cancer Causes Control. 25(3):293-307.
• Pubmed ID:
  24337772
• Pubmed Central ID:
  PMC3946243
• Document Type:
  Journal Article
• Funding:
  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 ; N01-PC-67000/PC/NCI NIH HHS/United States ; R01 CA078682/CA/NCI NIH HHS/United States ; R01 CA140002/CA/NCI NIH HHS/United States
• Volume:
  25
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:fab0cc95193574d09723c1e04575fdb1a30be2544223fadd263665b78bba9120
• Download URL:
  https://stacks.cdc.gov/view/cdc/29869/cdc_29869_DS1.pdf
• File Type:
  [PDF - 1.08 MB ]