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- W2008372806 abstract "Abstract Purpose: Triple negative breast cancer (TNBC), which lacks treatment targets for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), has been associated with African-American race, BRCA1/2 mutations, TP53 mutations, and poor prognosis. However, the etiology of TNBC remained unknown, which represents a critical barrier in reducing breast cancer mortality. Therefore, we designed a case-only study to test combined genetic and nutritional risk models of TNBC. Methods: In 354 breast cancer patients diagnosed between 1998 and 2004, we evaluated 18 DNA-repair non-synonymous single nucleotide polymorphisms (nsSNPs) using the Sequenom MassARRAY system. The 110-item Block 1998 food frequency questionnaire was used to evaluate dietary/nutritional intakes. The Multivariate Adaptive Regression Splines (MARS)-logit models were used to define nutritional intakes cut-offs for their associations with TNBC. Results: TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or 3 micronutrients (zinc, folate, and β-carotene). Combined DNA-repair risk genotypes and lower micronutrient intakes had a significant dosage-dependent association with TNBC (p<0.001): ORs=2.77 (95%CI=1.01-7.64), 9.57 (95%CI=2.87-31.84), and 20.78 (95%CI=2.46-175.71) for 2, 3, and at least 4 risk factors combined, respectively. Conclusion: To the best of our knowledge, this is the first study to demonstrate multiple DNA repair nsSNPs and nutritional factors are associated with TNBC. Our results suggest that dietary modulation and micronutrient supplementation may have implication in preventing or reversing TNBC, particularly in genetically susceptible women. Citation Format: Jennifer Hu, Eunkyung Lee, Glenn Allen. DNA repair and nutritional risk models of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 10. doi:10.1158/1538-7445.CANSUSC14-10" @default.
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- W2008372806 date "2014-12-01" @default.
- W2008372806 modified "2023-09-24" @default.
- W2008372806 title "Abstract 10: DNA repair and nutritional risk models of triple-negative breast cancer" @default.
- W2008372806 doi "https://doi.org/10.1158/1538-7445.cansusc14-10" @default.
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