"Short anogenital distance is associated with testicular germ cell tumour development".

Testicular Germ Cell Tumour (TGCT) is a multifactorial disease in which various genetic and environmental factors play a role. TGCT is part of the testicular dysgenesis syndrome (TDS) which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance (AGD).

The primary objective was to examine AGD in TGCT cases and healthy fertile controls. The secondary objective was to assess the (CAG)n polymorphism of the androgen receptor gene (AR) in relationship with AGDs and TGCT development.

156 TGCT patients and 110 tumour-free normozoospermic controls of Spanish origin. All subjects underwent full andrological work-up (including semen and hormone analysis) and genetic analysis (Androgen Receptor (CAG)n). The main outcome measures were the anopenile distance (AGDap), the anoscrotal distance (AGDas) and AR(CAG)n.

We observed significantly shorter AGDs in the group of TGCT patients in respect to controls (p<0.001) independently from sperm count and testis histology. Threshold values, applicable only to our cohort, were calculated for AGDs with the best sensitivity and specificity. Subjects with AGDap and AGDas below threshold showed a significantly increased risk for TGCT (OR=4.97, 95% CI=2.01-12.33, p=0.001 and OR=4.11, 95% CI=1.89-8.92, p≤0.001, respectively). No significant correlation was observed between AR(CAG)n polymorphism and AGDs. The median values of the AR(CAG)n were similar between cases and controls, excluding a major role for this polymorphism in the etiopathogenesis of these TDS components.

Ours, is the first study focusing on AGDs in TGCT patients. We identified short AGDs (which is a surrogate biomarker of androgen action during foetal life) as a significant risk factor for this disease. After further validation of our preliminary data, AGD measurement could become part of TGCT screening in order to better define those individuals who would benefit from long-term active follow-up.

Andrology. 2020 Jul 19 [Epub ahead of print]

Daniel Moreno-Mendoza, Elena Casamonti, Antoni Riera-Escamilla, Sara Pietroforte, Giovanni Corona, Eduardo Ruiz-Castañe, Csilla Krausz

Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Spain., Department of Biomedical, Experimental and Clinical Sciences "Mario Serio". University of Florence, Florence, Italy., Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Bologna, Italy.