Identification of a novel germline missense mutation of the androgen receptor in African American men with familial prostate cancer

作     者：Si-Yi Hu Tao Liu Zhen-Zhen Liu Elisa Ledet Cruz Velasco-Gonzalez Diptasri M Mandal Shahriar Koochekpour 

作者机构：Stanley S Scott Cancer Center Louisiana State University Health Sciences Center New Orleans LA 70112 USA Department of Genetics Louisiana State University Health Sciences Center New Orleans LA 70112 USA School of Public Health Louisiana State University Health Sciences Center New Orleans LA 70112 USA 4Department of Microbiology and Immunology Department of Urology Department of Biochemistry and Molecular Biology Louisiana State University Healt Sciences Center New Orleans LA 70112 USA 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2010年第12卷第3期

页      面：336-343,I0008,I0009页

核心收录：

学科分类：10[医学] 

基　　金：National Cancer Institute, NCI, (R03CA097778, R21CA120625, R21CA143589, R21CA149137) National Center for Research Resources, NCRR, (P20RR021970) National Institute on Minority Health and Health Disparities, NIMHD, (R01MD005824) 

主　　题：African Americans androgen receptor familial prostate cancer germline mutation 

摘      要：Race, family history and age are the unequivocally accepted risk factors for prostate cancer （PCa）. Androgen receptor （AR）-dependent signaling is an important element in prostate carcinogenesis and its progression to metastatic disease. We examined the possibility of genomic changes in the AR in association with familial PCa in African Americans who have a higher incidence and mortality rate and a clinically more aggressive disease presentation than Caucasians. Genomic DNAs of 60 patients from 30 high-risk African American and Caucasian families participating in the Louisiana State University Health Sciences Center genetic linkage study of PCa were studied. Exon-specific polymerase-chain reaction, bi-directional automated sequencing and restriction enzyme genotyping were used to analyze for mutations in the coding region of the AR gene. We identified a germline AR （A1675T） （T559S） substitution mutation in the DNA-binding domain in three PCa-affected members of an African- American family with a history of early-onset disease. The present study describes the first AR germline mutation in an African-American family with a history of familial PCa. The AR （T559S） mutation may contribute to the disease by altering AR DNA-binding affinity and/or its response to androgens, non-androgenic steroids or anti-androgens. Additional studies will be required to define the frequency and contribution of the AR （A 1675T） allele to early-onset and/or familial PCa in African Americans.