4.4 Article

Short anogenital distance is associated with testicular germ cell tumour development

Journal

ANDROLOGY
Volume 8, Issue 6, Pages 1770-1778

Publisher

WILEY
DOI: 10.1111/andr.12863

Keywords

anogenital distance (AGD); testicular germ cell tumour (TGCT); androgen receptor (AR); testicular dysgenesis syndrome (TDS); CAG repeat; testis cancer

Categories

Funding

  1. Instituto de Salud Carlos III [FIS/FEDER-PI14/01250, FIS/FEDER-PI17/01822]
  2. Fundacion Merck Salud

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Background Testicular germ cell tumour is a multifactorial disease in which various genetic and environmental factors play a role. Testicular germ cell tumour is part of the testicular dysgenesis syndrome which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance. Objectives The primary objective was to examine anogenital distance in testicular germ cell tumour cases and healthy fertile controls. The secondary objective was to assess the (CAG)n polymorphism of the Androgen Receptor gene in relationship with anogenital distances and testicular germ cell tumour development. Material and Methods 156 testicular germ cell tumour patients and 110 tumour-free normozoospermic controls of Spanish origin. All subjects underwent full andrological workup (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) andAR(CAG)n. Result We observed significantly shorter anogenital distances in the group of testicular germ cell tumour patients in respect to controls (P < .001) independently from sperm count and testis histology. Threshold values, applicable only to our cohort, were calculated for anogenital distances with the best sensitivity and specificity. Subjects with AGDap and AGDas below threshold showed a significantly increased risk for testicular germ cell tumour (OR = 4.97, 95% CI = 2.01-12.33,P = .001 and OR = 4.11, 95% CI = 1.89-8.92,P <= .001, respectively). No significant correlation was observed betweenAR(CAG)n polymorphism and anogenital distances. The median values of theAR(CAG)n were similar between cases and controls, excluding a major role for this polymorphism in the etiopathogenesis of these testicular dysgenesis syndrome components. Conclusions Ours is the first study focusing on anogenital distances in testicular germ cell tumour patients. We identified short anogenital distances (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, anogenital distance measurement could become part of testicular germ cell tumour screening in order to better define those individuals who would benefit from long-term active follow-up.

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