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PUBLICATION: Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium. Carcinogenesis 2016 in press.

by Zhang J, Yao S, Hu Q, Zhu QQ, Liu S, Lunetta KL, Haddad SA, Yang N, Shen H, Hong C-C, Sucheston-Campbell L, Ruiz-Narvaez EA, Bensen JT, Troester MA, Bandera EV, Rosenberg L, Haiman CA, Olshan AF, Palmer JR, Ambrosone CB.
Tue, Aug 2nd 2016 05:05 pm

 ABSTRACT: The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Dysfunction of the Hippo pathway components has been linked with breast cancer stem cell (CSC) regulation, as well as breast tumor progression and metastasis. TAZ, a key component of the Hippo pathway, is highly expressed in triple negative breast cancer (TNBC); however, the associations of genetic variations in this important pathway with breast cancer risk remain largely unexplored. Here, we analyzed 8,309 germline variants in 15 genes from the Hippo pathway with a total of 3,663 cases and 4,687 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.  Odds ratios (ORs) were estimated using logistic regression for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses by ER status.  The Hippo signaling pathway was significantly associated with ER-negative breast cancer (pathway-level p=0.02). Gene-based analyses revealed that CDH1 was responsible for the pathway association (p < 0.01), with rs4783673 inCDH1 statistically significant after gene-level adjustment for multiple comparisons (p = 9.2x10-5, corrected p = 0.02).  rs142697907 in PTPN14 was associated with ER-positive breast cancer and rs2456773 in CDK1 with ER-negativity in case-only analysis after gene-level correction for multiple comparisons  (corrected p < 0.05). In conclusion, common genetic variations in the Hippo signaling pathway may contribute to both ER-negative and ER+ breast cancer risk in AA women. 

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