TGF-B signaling pathway, ER-a and the heterogeneity of breast cancer risk among hispanic and non-hispanic white women.

• Main Author: Boone, Stephanie Denkhoff
• Format: Text
• Language: English
• Published: ThinkIR: The University of Louisville's Institutional Repository 2013
• Subjects: Breast cancer; Genetic admixture; Genetic susceptibility; TGF-B signaling pathway; Hispanic; Non-hispanic; Breast > Cancer > Genetic aspects; Orca
• Online Access: https://ir.library.louisville.edu/etd/127; https://doi.org/10.18297/etd/127; https://ir.library.louisville.edu/context/etd/article/1126/viewcontent/5433.pdf

Many risk factors for breast cancer differ between race/ethnic groups. Few studies have included Hispanic women: a genetically admixed population that differs from other ethnic groups for breast cancer incidence, survival, and tumor phenotype. The objective of this study was to determine if genetic variation in ERa and TGF-ß signaling genes (TGF-ß1, TGF-ßR1, RUNX1, RUNX2, RUNX3) is associated with breast cancer risk, and if these associations differ between Hispanic and non-Hispanic white women (NHW). Data from The Breast Cancer Health Disparities (BCHD) study were used. BCHD is a multi-site consortium including two case-control studies within the U.S. and one in Mexico. A total of 3,524 cases (NHW=1,431; Hispanic=2,093) and 4,209 population-based controls (NHW=1,599; Hispanic=2,610) had available DNA. In-person interviews collected information on non-genetic risk factors. Single nucleotide polymorphisms (SNPs) in TGF-ß, RUNX and ERa genes were determined using an Illumina platform and PCR. Associations with breast cancer risk were evaluated using multivariable logistic regression, adjusting for study site, age, and Native American genetic ancestry. Associations with breast cancer phenotypes (ER/PR status) were also evaluated and a genetic risk score (GRS) was calculated to determine the cumulative effect of selected SNPs. Two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG=1.15 95% CI 1.04-1.26) and TGF-ß1 (rs4803455 ORCA/AA=0.89 95% CI 0.81-0.98). RUNX3 (rs906296) was specifically associated with risk in pre-menopausal women (p=0.002) and in those with moderate to high Native American ancestry. There was a significant interaction between Native American ancestry and RUNX1 (rs7279383, p=0.04). Four RUNX SNPs were associated with an increased risk of ER-/PR- (n=3) and ER-/PR+ (n=1) tumors. A GRS including 6 SNPs (range=0-10 alleles) across ERa and TGF-ß signaling genes was positively associated with overall risk (per allele OR=1.14 95% CI 1.04-1.25), as well as ER+, but not ...