TY - JOUR
T1 - Genetic variations in the Hippo signaling pathway and breast cancer risk in African American women in the AMBER Consortium
AU - Zhang, Jianmin
AU - Yao, Song
AU - Hu, Qiang
AU - Zhu, Qianqian
AU - Liu, Song
AU - Lunetta, Kathryn L.
AU - Haddad, Stephen A.
AU - Yang, Nuo
AU - Shen, He
AU - Hong, Chi Chen
AU - Sucheston-Campbell, Lara
AU - Ruiz-Narvaez, Edward A.
AU - Bensen, Jeannette T.
AU - Troester, Melissa A.
AU - Bandera, Elisa V.
AU - Rosenberg, Lynn
AU - Haiman, Christopher A.
AU - Olshan, Andrew F.
AU - Palmer, Julie R.
AU - Ambrosone, Christine B.
N1 - Funding Information:
National Cancer Institute (NCI) (R21CA179693 to J. Z, P01CA151135 to J.R.P., C.B.A. and A.F.O., R01CA058420 to L.R., UM1CA164974 to L.R., R01CA098663 to J.R.P., R01CA100598 to C.B.A., P50CA58223 to M.A.T. and A.F.O.); the University Cancer Research Fund of North Carolina (M.A.T. and A.F.O.); the Breast Cancer Research Foundation (C.B.A.); the Roswell Park Alliance Foundation; and the American Cancer Society Research Scholar RSG-14-214-01-TBE (to J.Z.).
Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgw077
DO - 10.1093/carcin/bgw077
M3 - Article
C2 - 27485598
AN - SCOPUS:84991236925
SN - 0143-3334
VL - 37
SP - 951
EP - 956
JO - Carcinogenesis
JF - Carcinogenesis
IS - 10
M1 - bgw077
ER -