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

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

来源：Breast Cancer Research and Treatment, 2013, 141(2): 287-297.

DOI：10.1007/s10549-013-2690-z

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

The TGF-beta 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-beta 1, TGF-beta 2, TGF-beta R1, TGF-beta R2, TGF-beta R3, 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-beta 1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81-0.98). RUNX3 (rs906296) and TGF-beta R2 (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-beta and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-beta and RUNX genes and breast cancer risk among women of NA ancestry.

• 出版日期2013-9