title: Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of spermatogenesis following testicular germ cell cancer treatment.
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 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 × 106 ml-1 vs 16 × 106 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 × 106 ml-1 vs 10 × 106 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.
authors.affiliation: Reproductive Medicine Centre, Skane University Hospital, Malmö, Sweden.|Department of Oncology, Skane University Hospital, Malmö, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Bogefors
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Yvonne Lundberg
authors.initials: YL
authors.lastname: Giwercman
authors.affiliation: Department of Oncology, Skane University Hospital, Lund, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
authors.affiliation: Department of Oncology, Skane University Hospital, Lund, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Stahl
authors.affiliation: Department of Oncology, Skane University Hospital, Lund, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Cavallin-Stahl
authors.affiliation: Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cohn-Cedermark
authors.affiliation: Centre of Andrology and Sexual Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Arver
authors.affiliation: Reproductive Medicine Centre, Skane University Hospital, Malmö, Sweden.|Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D011237:Predictive Value of Tests; D011878:Radiotherapy / Q000009:adverse effects; D011944:Receptors, Androgen / Q000235:genetics*; D020127:Recovery of Function; D012661:Semen / Q000166:cytology; D013091:Spermatogenesis / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen