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Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer.
Clin Cancer Res. 1997 Sep; 3(9):1599-608.CC

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.

Authors+Show Affiliations

Department of Urology and The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9815849

Citation

Hakimi, J M., et al. "Androgen Receptor Variants With Short Glutamine or Glycine Repeats May Identify Unique Subpopulations of Men With Prostate Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 3, no. 9, 1997, pp. 1599-608.
Hakimi JM, Schoenberg MP, Rondinelli RH, et al. Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. Clin Cancer Res. 1997;3(9):1599-608.
Hakimi, J. M., Schoenberg, M. P., Rondinelli, R. H., Piantadosi, S., & Barrack, E. R. (1997). Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 3(9), 1599-608.
Hakimi JM, et al. Androgen Receptor Variants With Short Glutamine or Glycine Repeats May Identify Unique Subpopulations of Men With Prostate Cancer. Clin Cancer Res. 1997;3(9):1599-608. PubMed PMID: 9815849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. AU - Hakimi,J M, AU - Schoenberg,M P, AU - Rondinelli,R H, AU - Piantadosi,S, AU - Barrack,E R, PY - 1998/11/17/pubmed PY - 1998/11/17/medline PY - 1998/11/17/entrez SP - 1599 EP - 608 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 3 IS - 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/9815849/Androgen_receptor_variants_with_short_glutamine_or_glycine_repeats_may_identify_unique_subpopulations_of_men_with_prostate_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=9815849 DB - PRIME DP - Unbound Medicine ER -