English 
Italian Polimorfismi dei geni KLK3, RASA1 e NAALADL2: rischio di cancro alla prostata, aggressività della neoplasia e livelli sierici dell’Antigene Prostatico-Specifico
Polymorphisms of KLK3, RASA1 and NAALADL2 genes: prostate cancer risk, aggressiveness of neoplasia and serum PSA levels
AUTORI
1Dipartimento di Medicina e Dipartimento di Medicina di Laboratorio, Università di Padova, Italia
2Dipartimento di Scienze Biomediche e Dipartimento di Medicina di Laboratorio, Università di Padova, Italia
3Dipartimento di Medicina di Laboratorio, Università di Padova, Italia
4Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Italia
ABSTRACT
Polymorphisms of KLK3, RASA1 and NAALADL2 genes: prostate cancer risk, aggressiveness of neoplasia and serum PSA levels
Background: prostate cancer (Pca) is the second most common cancer among men and the sixth leading cause of death due to cancer among men worldwide. We aimed to verify if serum PSA levels and PCa risk/aggressiveness are modulated by polymorphisms of KLK3, RASA1 and NAALADL2 genes.
Methods: 1058 men have been studied; they consecutively underwent prostate biopsy for clinical suspicion of PCa. PCa was histologically diagnosed in 401 and ruled out in 657 men. Gleason score in PCa patients was ≤6 in 261, 7 in 83 and >7 in the remaining 57 PCa. tPSA and f/tPSA levels were determined. Four polymorphisms were studied: rs35148638 (RASA1), rs78943174 (NAALADL2), rs2735839 and rs17632542 (KLK3).
Results: PCa diagnosis was significantly predicted by the KLK3 rs17632542 polymorphism (p<0.001), tPSA (p<0.001) and f/tPSA (p<0.001). Carriers of the KLK3 rs17632542C rare allele had a significantly higher risk of PCa (p<0.001) (OR 2.1, 95% CI 1.40-3.19). Gleason score >7 was associated with increased tPSA (p<0.001), decreased f/tPSA (p=0.003) and the KLK3 rs2735839 A rare allele (p= 0.004). In controls, tPSA was significantly lower in subjects bearing NAALADL2 rs78943174T rare allele (p=0.029). f/tPSA was higher in subjects with the KLK3 rs17632542C rare allele (p<0.001) and with the RASA1 rs35148638 C/C genotypes (p=0.009). In PCa subjects, tPSA was not associated with the polymorphisms studied.
Conclusions: KLK3 rs17632542 and rs2735839 polymorphisms were significantly associated with the risk and aggressiveness of PCa respectively. NAALADL2, KLK3 rs17632542 and RASA1 polymorphisms were correlated with tPSA and f/tPSA serum levels, suggesting a genetically-based PSA expected values in absence of tumor. These results suggest a potential role of these polymorphisms as biomarkers for PCa in association with the diagnostic and prognostic indexes currently recognized.