title: 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.
abstract: 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.
authors: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT, 84108, USA, Marty.Slattery@hsc.utah.edu.
authors: Martha L
authors: ML
authors: Slattery
authors: Abbie
authors: A
authors: Lundgreen
authors: Marianna C
authors: MC
authors: Stern
authors: Lisa
authors: L
authors: Hines
authors: Roger K
authors: RK
authors: Wolff
authors: Anna R
authors: AR
authors: Giuliano
authors: Kathy B
authors: KB
authors: Baumgartner
authors: Esther M
authors: EM
authors: John
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D054625:Healthcare Disparities; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012495:San Francisco / Q000453:epidemiology; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D016212:Transforming Growth Factor beta