Purpose: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases. Methods: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples. Results: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number. Conclusions: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.
PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile / Faja, F.; Finocchi, F.; Carlini, T.; Rizzo, F.; Pallotti, F.; Spaziani, M.; Balercia, G.; Lenzi, A.; Paoli, D.; Lombardo, F.. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - 44:10(2021), pp. 2273-2284-2284. [10.1007/s40618-021-01534-3]