American Journal of Epidemiology Vol. 155, No. 10 : 883-890
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health
HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW |
Androgen Receptor CAG Repeats and Prostate Cancer
From the Department of Epidemiology and Biostatistics, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106-4945 (e-mail: witte{at}darwin.cwru.edu).
ABSTRACT
Prostate cancer is the most common nonskin malignancy and the second leading cause of cancer deaths among men in the United States. Prostate cancer ([Mendelian Inheritance in Man 176807]) has a complex etiology; presently, age, ethnicity, and family history are the most consistently reported risk factors associated with disease. Other potential risk and protective factors have also been suggested. Androgen, acting through the androgen receptor (AR) is helpful in preserving the normal function and structure of the prostate. The AR ([Mendelian Inheritance in Man 313700]) is a structurally conserved member of the nuclear receptor superfamily of ligand-activated transcription factors. Androgens, such as testosterone, are strong tumor promoters, and work with the AR to augment the effect of any carcinogens present and stimulate cell division. The CAG repeats encode long glutamine homopolymeric amino acid chains in the amino-terminal domain of the AR gene. The authors focus on CAG repeat length because recent research suggests that men with shorter AR CAG lengths (e.g., 
22 repeats) are at a greater risk of developing prostate cancer than are those with longer variants. Among populations studied to date, African Americans appear to have the highest frequency of short CAG repeats. Several potential interactions have also been explored, including molecular interactions, androgen deprivation therapy, and prostate-specific antigen expression. CAG repeat length can be determined with high sensitivity and specificity. Presently, there is no recommended population screening for AR CAG repeat length.
epidemiology; prostatic neoplasms; receptors, androgen; trinucleotide repeats
Abbreviations: AR, androgen receptor; BPH, benign prostatic hypertrophy; CI, confidence interval; PCR, polymerase chain reaction; SBMA, spinal and bulbar muscular atrophy
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