UACA locus is associated with breast cancer chemoresistance and survival
Qianqian Zhu, Emily Schultz, Jirong Long, Janise M. Roh, Emily Valice, Cecile A. Laurent, Kelly H. Radimer, Li Yan, Isaac J. Ergas, Warren Davis, Dilrini K. Ranatunga, Shipra Gandhi, Marilyn L. Kwan, Ping‐Ping Bao, Wei Zheng, Xiao‐Ou Shu, Christine B. Ambrosone, Song Yao, Lawrence H. Kushi
Abstract
Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ([Formula: see text]). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, [Formula: see text]). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ([Formula: see text]). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.