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Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of spermatogenesis following testicular germ cell cancer treatment

Leandersson Bogefors, Karolina LU ; Giwercman, Yvonne Lundberg LU ; Eberhard, Jakob LU ; Ståhl, Olof LU ; Cavallin-Ståhl, Eva LU ; Cohn-Cedermark, Gabriella; Arver, Stefan and Giwercman, Aleksander LU (2017) In Asian Journal of Andrology 19(5). p.538-542
Abstract

Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients (n = 130) delivered ejaculates at the following time points: postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy (T0, T6, T12, T24, T36, and T60). The CAG lengths were categorized into... (More)

Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients (n = 130) delivered ejaculates at the following time points: postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy (T0, T6, T12, T24, T36, and T60). The CAG lengths were categorized into three groups, <22 CAG, 22-23 CAG, and >23 CAG, and the GGN tracts were also categorized into three groups, <23 GGN, 23 GGN, and >23 GGN. At T12, men with 22-23 CAG presented with a statistically significantly (P = 0.045) lower sperm concentration than those with other CAG numbers (8.4 × 10 6 ml-1 vs 16 × 10 6 ml-1 ; 95% CI: 1.01-2.65). This association was robust to omitting adjustment for treatment type and sperm concentration at T0 (P = 0.021; 3.7 × 10 6 ml-1 vs 10 × 10 6 ml-1 ; 95% CI: 1.13-4.90). The same trends were observed for total sperm number. The least active AR variant seems to be associated with a more rapid recovery of spermatogenesis. This finding adds to our understanding of the biology of postcancer therapy recovery of fertility in males and has clinical implications.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Asian Journal of Andrology
volume
19
issue
5
pages
538 - 542
publisher
Nature Publishing Group
external identifiers
  • wos:000407906900007
  • scopus:85027848938
ISSN
1008-682X
DOI
10.4103/1008-682X.191126
language
English
LU publication?
yes
id
0038b78d-8cc5-4624-b4de-baceb8fbdeed
date added to LUP
2017-04-06 10:27:31
date last changed
2018-01-07 11:58:12
@article{0038b78d-8cc5-4624-b4de-baceb8fbdeed,
  abstract     = {<p>Spermatogenesis is an androgen-regulated process that depends on the action of androgen receptor (AR). Sperm production may be affected in men treated for testicular cancer (TC), and it is important to identify the factors influencing the timing of spermatogenesis recovery following cancer treatment. It is known that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the aim of this study is to investigate if the CAG and GGN polymorphisms in the AR gene predict recovery of sperm production after TC treatment. TC patients (n = 130) delivered ejaculates at the following time points: postorchiectomy and at 6, 12, 24, 36, and 60 months posttherapy (T0, T6, T12, T24, T36, and T60). The CAG lengths were categorized into three groups, &lt;22 CAG, 22-23 CAG, and &gt;23 CAG, and the GGN tracts were also categorized into three groups, &lt;23 GGN, 23 GGN, and &gt;23 GGN. At T12, men with 22-23 CAG presented with a statistically significantly (P = 0.045) lower sperm concentration than those with other CAG numbers (8.4 × 10 6 ml-1 vs 16 × 10 6 ml-1 ; 95% CI: 1.01-2.65). This association was robust to omitting adjustment for treatment type and sperm concentration at T0 (P = 0.021; 3.7 × 10 6 ml-1 vs 10 × 10 6 ml-1 ; 95% CI: 1.13-4.90). The same trends were observed for total sperm number. The least active AR variant seems to be associated with a more rapid recovery of spermatogenesis. This finding adds to our understanding of the biology of postcancer therapy recovery of fertility in males and has clinical implications.</p>},
  author       = {Leandersson Bogefors, Karolina and Giwercman, Yvonne Lundberg and Eberhard, Jakob and Ståhl, Olof and Cavallin-Ståhl, Eva and Cohn-Cedermark, Gabriella and Arver, Stefan and Giwercman, Aleksander},
  issn         = {1008-682X},
  language     = {eng},
  number       = {5},
  pages        = {538--542},
  publisher    = {Nature Publishing Group},
  series       = {Asian Journal of Andrology},
  title        = {Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of spermatogenesis following testicular germ cell cancer treatment},
  url          = {http://dx.doi.org/10.4103/1008-682X.191126},
  volume       = {19},
  year         = {2017},
}