Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer

Janette M. Hakimi, Mark P. Schoenberg, Rachel H. Rondinelli, Steven Piantadosi, Evelyn R. Barrack

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

The androgen receptor (AR) contains glutamine (CAG) and glycine (GGC) repeats that are each polymorphic in length. We screened clinically localized prostate cancers for somatic mutations in the length of the CAG and GGC repeats in the AR gene and characterized the length of these repeats in the germ-line AR gene. Somatic mutations were rare, and the range of germ-line repeat lengths in men with prostate cancer was within the range of normal in the general population. Most allele frequencies in Caucasian men with clinical prostate cancer were remarkably comparable to those in the general Caucasian population. However, a subpopulation of the men with clinical prostate cancer had a substantially higher frequency of AR alleles with 16 or 17 CAGs (6 of 59 men, 10%) than did the general population (6 of 370 alleles, 1.6%), and a different subpopulation of the men with prostate cancer had a higher frequency of AR alleles with 12 or 13 GGCs (7 of 54 men, 13%) than did the general population (1 of 110 alleles, 0.9%). Of the men with prostate cancer who had an AR gene with 16 or 17 CAGs, 83% had lymph node-positive disease, despite the lack of clinical evidence of metastatic spread. This suggests that a short AR CAG allele may be a risk factor for the development of clinically unsuspected lymph node- positive prostate cancer among men undergoing radical prostatectomy and raises the question of whether this short repeat length played an active role in the development of aggressive prostate cancer. The odds of having a germ-line AR gene with a short CAG repeat (≤17 CAGs) were substantially higher in Caucasian men with lymph node-positive prostate cancer than in Caucasian men with lymph node-negative disease or in the general Caucasian population. The odds of having a short germ-line AR CAG were the same for men with lymph node-negative prostate cancer as for the general Caucasian population. The odds of having a germ-line AR gene with a short glycine repeat (≤14 GGCs) were substantially higher in men with prostate cancer than in the general population, but the frequency of alleles with a short GGC repeat was the same in men with lymph node-positive versus lymph node- negative disease. This suggests that a short GGC repeat may be a risk factor for the development of clinical prostate cancer, a hypothesis that needs to be tested in cohort and case-control studies.

Original languageEnglish (US)
Pages (from-to)1599-1608
Number of pages10
JournalClinical Cancer Research
Volume3
Issue number9
StatePublished - Sep 1997
Externally publishedYes

Fingerprint

Androgen Receptors
Glutamine
Glycine
Prostatic Neoplasms
Lymph Nodes
Germ Cells
Alleles
Population
Genes
Gene Frequency
Mutation
Prostatectomy
Case-Control Studies
Reference Values

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. / Hakimi, Janette M.; Schoenberg, Mark P.; Rondinelli, Rachel H.; Piantadosi, Steven; Barrack, Evelyn R.

In: Clinical Cancer Research, Vol. 3, No. 9, 09.1997, p. 1599-1608.

Research output: Contribution to journalArticle

Hakimi, Janette M. ; Schoenberg, Mark P. ; Rondinelli, Rachel H. ; Piantadosi, Steven ; Barrack, Evelyn R. / Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. In: Clinical Cancer Research. 1997 ; Vol. 3, No. 9. pp. 1599-1608.
@article{bb60b96e619b4d3ba29af6ab776b2e4d,
title = "Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer",
abstract = "The androgen receptor (AR) contains glutamine (CAG) and glycine (GGC) repeats that are each polymorphic in length. We screened clinically localized prostate cancers for somatic mutations in the length of the CAG and GGC repeats in the AR gene and characterized the length of these repeats in the germ-line AR gene. Somatic mutations were rare, and the range of germ-line repeat lengths in men with prostate cancer was within the range of normal in the general population. Most allele frequencies in Caucasian men with clinical prostate cancer were remarkably comparable to those in the general Caucasian population. However, a subpopulation of the men with clinical prostate cancer had a substantially higher frequency of AR alleles with 16 or 17 CAGs (6 of 59 men, 10{\%}) than did the general population (6 of 370 alleles, 1.6{\%}), and a different subpopulation of the men with prostate cancer had a higher frequency of AR alleles with 12 or 13 GGCs (7 of 54 men, 13{\%}) than did the general population (1 of 110 alleles, 0.9{\%}). Of the men with prostate cancer who had an AR gene with 16 or 17 CAGs, 83{\%} had lymph node-positive disease, despite the lack of clinical evidence of metastatic spread. This suggests that a short AR CAG allele may be a risk factor for the development of clinically unsuspected lymph node- positive prostate cancer among men undergoing radical prostatectomy and raises the question of whether this short repeat length played an active role in the development of aggressive prostate cancer. The odds of having a germ-line AR gene with a short CAG repeat (≤17 CAGs) were substantially higher in Caucasian men with lymph node-positive prostate cancer than in Caucasian men with lymph node-negative disease or in the general Caucasian population. The odds of having a short germ-line AR CAG were the same for men with lymph node-negative prostate cancer as for the general Caucasian population. The odds of having a germ-line AR gene with a short glycine repeat (≤14 GGCs) were substantially higher in men with prostate cancer than in the general population, but the frequency of alleles with a short GGC repeat was the same in men with lymph node-positive versus lymph node- negative disease. This suggests that a short GGC repeat may be a risk factor for the development of clinical prostate cancer, a hypothesis that needs to be tested in cohort and case-control studies.",
author = "Hakimi, {Janette M.} and Schoenberg, {Mark P.} and Rondinelli, {Rachel H.} and Steven Piantadosi and Barrack, {Evelyn R.}",
year = "1997",
month = "9",
language = "English (US)",
volume = "3",
pages = "1599--1608",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer

AU - Hakimi, Janette M.

AU - Schoenberg, Mark P.

AU - Rondinelli, Rachel H.

AU - Piantadosi, Steven

AU - Barrack, Evelyn R.

PY - 1997/9

Y1 - 1997/9

N2 - The androgen receptor (AR) contains glutamine (CAG) and glycine (GGC) repeats that are each polymorphic in length. We screened clinically localized prostate cancers for somatic mutations in the length of the CAG and GGC repeats in the AR gene and characterized the length of these repeats in the germ-line AR gene. Somatic mutations were rare, and the range of germ-line repeat lengths in men with prostate cancer was within the range of normal in the general population. Most allele frequencies in Caucasian men with clinical prostate cancer were remarkably comparable to those in the general Caucasian population. However, a subpopulation of the men with clinical prostate cancer had a substantially higher frequency of AR alleles with 16 or 17 CAGs (6 of 59 men, 10%) than did the general population (6 of 370 alleles, 1.6%), and a different subpopulation of the men with prostate cancer had a higher frequency of AR alleles with 12 or 13 GGCs (7 of 54 men, 13%) than did the general population (1 of 110 alleles, 0.9%). Of the men with prostate cancer who had an AR gene with 16 or 17 CAGs, 83% had lymph node-positive disease, despite the lack of clinical evidence of metastatic spread. This suggests that a short AR CAG allele may be a risk factor for the development of clinically unsuspected lymph node- positive prostate cancer among men undergoing radical prostatectomy and raises the question of whether this short repeat length played an active role in the development of aggressive prostate cancer. The odds of having a germ-line AR gene with a short CAG repeat (≤17 CAGs) were substantially higher in Caucasian men with lymph node-positive prostate cancer than in Caucasian men with lymph node-negative disease or in the general Caucasian population. The odds of having a short germ-line AR CAG were the same for men with lymph node-negative prostate cancer as for the general Caucasian population. The odds of having a germ-line AR gene with a short glycine repeat (≤14 GGCs) were substantially higher in men with prostate cancer than in the general population, but the frequency of alleles with a short GGC repeat was the same in men with lymph node-positive versus lymph node- negative disease. This suggests that a short GGC repeat may be a risk factor for the development of clinical prostate cancer, a hypothesis that needs to be tested in cohort and case-control studies.

AB - The androgen receptor (AR) contains glutamine (CAG) and glycine (GGC) repeats that are each polymorphic in length. We screened clinically localized prostate cancers for somatic mutations in the length of the CAG and GGC repeats in the AR gene and characterized the length of these repeats in the germ-line AR gene. Somatic mutations were rare, and the range of germ-line repeat lengths in men with prostate cancer was within the range of normal in the general population. Most allele frequencies in Caucasian men with clinical prostate cancer were remarkably comparable to those in the general Caucasian population. However, a subpopulation of the men with clinical prostate cancer had a substantially higher frequency of AR alleles with 16 or 17 CAGs (6 of 59 men, 10%) than did the general population (6 of 370 alleles, 1.6%), and a different subpopulation of the men with prostate cancer had a higher frequency of AR alleles with 12 or 13 GGCs (7 of 54 men, 13%) than did the general population (1 of 110 alleles, 0.9%). Of the men with prostate cancer who had an AR gene with 16 or 17 CAGs, 83% had lymph node-positive disease, despite the lack of clinical evidence of metastatic spread. This suggests that a short AR CAG allele may be a risk factor for the development of clinically unsuspected lymph node- positive prostate cancer among men undergoing radical prostatectomy and raises the question of whether this short repeat length played an active role in the development of aggressive prostate cancer. The odds of having a germ-line AR gene with a short CAG repeat (≤17 CAGs) were substantially higher in Caucasian men with lymph node-positive prostate cancer than in Caucasian men with lymph node-negative disease or in the general Caucasian population. The odds of having a short germ-line AR CAG were the same for men with lymph node-negative prostate cancer as for the general Caucasian population. The odds of having a germ-line AR gene with a short glycine repeat (≤14 GGCs) were substantially higher in men with prostate cancer than in the general population, but the frequency of alleles with a short GGC repeat was the same in men with lymph node-positive versus lymph node- negative disease. This suggests that a short GGC repeat may be a risk factor for the development of clinical prostate cancer, a hypothesis that needs to be tested in cohort and case-control studies.

UR - http://www.scopus.com/inward/record.url?scp=0030873595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030873595&partnerID=8YFLogxK

M3 - Article

C2 - 9815849

AN - SCOPUS:0030873595

VL - 3

SP - 1599

EP - 1608

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 9

ER -