Androgen receptor CAG repeat lengths in prostate cancer: Correlation with age of onset Journal Article

Authors: Hardy, D. O.; Scher, H. I.; Bogenreider, T.; Sabbatini, P.; Zhang, Z. F.; Nanus, D. M.; Catterall, J. F.
Article Title: Androgen receptor CAG repeat lengths in prostate cancer: Correlation with age of onset
Abstract: The androgen receptor (AR) is a structurally conserved member of the nuclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic; the average number is 22 in Caucasian males. Expansion of CAG repeats in the AR has clinical implications for human disease. As androgen influences prostate cancer growth, polymorphisms in CAG repeat length may affect the clinical course of patients with prostate cancer. To test for an association between clinical parameters of human prostate cancer and CAG repeat length, we analyzed normal lymphocyte DNA from 109 patients. The CAG region of the AR was amplified by the PCR. Reaction products were then amplified using end-labeled internal primers, cut at the internal PstI site and assayed on sequencing gels using a sequence ladder as a size standard. Sequence analysis of several samples validated this method for measurement of CAG repeat number. The median age of patients was 63 yr (range, 42-83), with 104 Caucasian, 2 African American, 1 Asian, and 2 other racial origin. The median repeat length was 25 for patients with stage A, 22 for patients with stage B, 22 for patients with stage C, and 23 for patients presenting with stage D disease. A significant correlation between CAG repeat length and age at onset was observed, whereas correlations with stage, level of prostate- specific antigen at diagnosis, and time to prostate-specific antigen relapse were not significant. Shorter CAG repeat lengths may be associated with the development of prostate cancer in men at a younger age. These data suggest that CAG repeat length can affect the risk of developing prostate cancer.
Keywords: adult; aged; aged, 80 and over; middle aged; major clinical study; polymerase chain reaction; prostate specific antigen; age factors; prostate cancer; prostate-specific antigen; prostatic neoplasms; transcription regulation; amino acid sequence; antigen specificity; growth regulation; transactivation; androgen receptor; receptors, androgen; point mutation; protein family; regression analysis; repetitive sequences, nucleic acid; dna polymorphism; tandem repeat; humans; human; male; priority journal; article
Journal Title: Journal of Clinical Endocrinology and Metabolism
Volume: 81
Issue: 12
ISSN: 0021-972X
Publisher: Oxford University Press  
Date Published: 1996-12-01
Start Page: 4400
End Page: 4405
Language: English
DOI: 10.1210/jc.81.12.4400
PUBMED: 8954049
PROVIDER: scopus
Notes: Thomas Bogenrieder's last name is misspelled in the original publication -- Source: Scopus
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MSK Authors
  1. Paul J Sabbatini
    201 Sabbatini
  2. Howard Scher
    837 Scher
  3. Zuo-Feng Zhang
    96 Zhang
  4. David M. Nanus
    40 Nanus