Susceptibility-Associated Genetic Variation in Contributes to Prostate Cancer Initiation and Progression

Overview

Journal Cancer Res

Specialty Oncology

Date 2021 Feb 26

PMID 33632899

Citations 3

Authors

Dong Han

Jude N Owiredu

Bridget M Healy

Muqing Li

Maryam Labaf

Jocelyn S Steinfeld

Susan Patalano

Shuai Gao

Mingyu Liu

Jill A Macoska

Kourosh Zarringhalam

Kellee R Siegfried

Xin Yuan

Timothy R Rebbeck

Changmeng Cai

Affiliations

Soon will be listed here.

Abstract

Although American men of European ancestry represent the largest population of patients with prostate cancer, men of African ancestry are disproportionately affected by prostate cancer, with higher prevalence and worse outcomes. These racial disparities in prostate cancer are due to multiple factors, but variations in genomic susceptibility such as SNP may play an important role in determining cancer aggressiveness and treatment outcome. Using public databases, we have identified a prostate cancer susceptibility SNP at an intronic enhancer of the neural precursor expressed, developmentally downregulated 9 () gene, which is strongly associated with increased risk of patients with African ancestry. This genetic variation increased expression of by modulating the chromatin binding of certain transcription factors, including ERG and NANOG. Moreover, NEDD9 displayed oncogenic activity in prostate cancer cells, promoting prostate cancer tumor growth and metastasis and . Together, our study provides novel insights into the genetic mechanisms driving prostate cancer racial disparities. SIGNIFICANCE: A prostate cancer susceptibility genetic variation in , which is strongly associated with the increased risk of patients with African ancestry, increases NEDD9 expression and promotes initiation and progression of prostate cancer..

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