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CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk

Bratt, O LU ; Borg, Åke LU ; Kristoffersson, U LU ; Lundgren, R; Zhang, Q X LU and Olsson, Håkan LU (1999) In British Journal of Cancer 81(4). p.6-672
Abstract

The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage, age at diagnosis and response to endocrine therapy. The study included 190 AR alleles from prostate cancer patients and 186 AR alleles from female control subjects. All were whites from southern Sweden. The frequency distribution of CAG repeat length was strikingly similar for cases and controls, and no significant correlation between CAG... (More)

The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage, age at diagnosis and response to endocrine therapy. The study included 190 AR alleles from prostate cancer patients and 186 AR alleles from female control subjects. All were whites from southern Sweden. The frequency distribution of CAG repeat length was strikingly similar for cases and controls, and no significant correlation between CAG repeat length and prostate cancer risk was detected. However, for men with non-hereditary prostate cancer (n = 160), shorter CAG repeats correlated with younger age at diagnosis (P = 0.03). There were also trends toward associations between short CAG repeats and high grade (P = 0.07) and high stage (P = 0.07) disease. Furthermore, we found that patients with long CAG repeats responded better to endocrine therapy, even after adjusting for pretreatment level of prostate-specific antigen and tumour grade and stage (P = 0.05). We conclude that short CAG repeats in the AR gene correlate with young age at diagnosis of prostate cancer, but not with higher risk of the disease. Selection of patients with early onset prostate cancer in case-control studies could therefore lead to an over-estimation of the risk of prostate cancer for men with short CAG repeats. An association between long CAG repeats and good response to endocrine therapy was also found, but the mechanism and clinical relevance are unclear.

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published
subject
keywords
Adult, Age Factors, Aged, Aged, 80 and over, Gonadotropin-Releasing Hormone, Humans, Male, Middle Aged, Prostatic Neoplasms, Receptors, Androgen, Risk, Trinucleotide Repeats
in
British Journal of Cancer
volume
81
issue
4
pages
5 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:0032885741
ISSN
0007-0920
DOI
10.1038/sj.bjc.6690746
language
English
LU publication?
yes
id
e7b42a49-540d-4dcb-8f01-882b4e5c954b
date added to LUP
2016-09-18 12:31:03
date last changed
2017-08-06 05:10:57
@article{e7b42a49-540d-4dcb-8f01-882b4e5c954b,
  abstract     = {<p>The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage, age at diagnosis and response to endocrine therapy. The study included 190 AR alleles from prostate cancer patients and 186 AR alleles from female control subjects. All were whites from southern Sweden. The frequency distribution of CAG repeat length was strikingly similar for cases and controls, and no significant correlation between CAG repeat length and prostate cancer risk was detected. However, for men with non-hereditary prostate cancer (n = 160), shorter CAG repeats correlated with younger age at diagnosis (P = 0.03). There were also trends toward associations between short CAG repeats and high grade (P = 0.07) and high stage (P = 0.07) disease. Furthermore, we found that patients with long CAG repeats responded better to endocrine therapy, even after adjusting for pretreatment level of prostate-specific antigen and tumour grade and stage (P = 0.05). We conclude that short CAG repeats in the AR gene correlate with young age at diagnosis of prostate cancer, but not with higher risk of the disease. Selection of patients with early onset prostate cancer in case-control studies could therefore lead to an over-estimation of the risk of prostate cancer for men with short CAG repeats. An association between long CAG repeats and good response to endocrine therapy was also found, but the mechanism and clinical relevance are unclear.</p>},
  author       = {Bratt, O and Borg, Åke and Kristoffersson, U and Lundgren, R and Zhang, Q X and Olsson, Håkan},
  issn         = {0007-0920},
  keyword      = {Adult,Age Factors,Aged,Aged, 80 and over,Gonadotropin-Releasing Hormone,Humans,Male,Middle Aged,Prostatic Neoplasms,Receptors, Androgen,Risk,Trinucleotide Repeats},
  language     = {eng},
  number       = {4},
  pages        = {6--672},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk},
  url          = {http://dx.doi.org/10.1038/sj.bjc.6690746},
  volume       = {81},
  year         = {1999},
}