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Carcinogenesis. 2016 Oct;37(10):951-956. doi: 10.1093/carcin/bgw077. Epub 2016 Aug 1.

Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium.

Author information

1
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
2
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
3
Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
4
Slone Epidemiology Center at Boston University, Boston, MA 02215, USA.
5
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
6
Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, The State University of New Jersey, New Brunswick, NJ 08901, USA, and.
7
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.

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 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; however, the associations of genetic variations in this important pathway with breast cancer risk remain largely unexplored. Here, we analyzed 8309 germline variants in 15 genes from the Hippo pathway with a total of 3663 cases and 4687 controls from the African American Breast Cancer Epidemiology and Risk Consortium. Odds ratios (ORs) were estimated using logistic regression for overall breast cancer, by estrogen receptor (ER) status (1983 ER positive and 1098 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 in CDH1 statistically significant after gene-level adjustment for multiple comparisons (P = 9.2×10(-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.

PMID:
27485598
PMCID:
PMC5035397
DOI:
10.1093/carcin/bgw077
[Indexed for MEDLINE]
Free PMC Article

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