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

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Asian Journal of Andrology 2017年第5期19卷 538-542页

作者： Karolina Bogefors Yvonne Lundberg Giwercman Jakob Eberhard Olof stahl eva cavallin-stahl Gabriella Cohn-Cedermark Stefan Arver Aleksander Giwercman Reproductive Medicine Centre Skane University Hospital Malmo Sweden Department of Oncology Skane University Hospital Malmo Sweden Department of Translational Medicine Lund University Malmo Sweden Department of Oncology Skane University Hospital Lund Sweden Radiumhemmet Karolinska HospitalStockholm Sweden Centre of Andrology and Sexual Medicine Karolinska Hospital Stockholm Sweden

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 （TO, 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 TO （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.

关键词： androgen receptor CAG and GGN repeat sperm number testicular cancer

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