GSTM1 and GSTT1 deletions in penile cancer are associated with TNM stage but not with HPV DNA status

Abstract

Deletions of the GSTT1 and GSTM1 are associated with chemical carcinogenesis and genitourinary malignancies like bladder cancer, where they correlate with increased tumor aggressiveness. In uterine cervical lesions, GSTT1 and GSTM1 deletions have also been suggested to facilitate the persistence of human papillomavirus (HPV) infection and HPV-induced carcinogenesis. This work addresses the hypothesis that GSTT1/GSTM1 deletions are associated with presence of HPV DNA and aggressiveness in penile cancer, a rare malignancy with HPV+ and HPV- subtypes. Tumor DNA samples and medical records from HPV+ and HPV- penile cancer patients were analyzed. Each sample was screened for GSTT1 and GSTM1 deletions and for the presence of HPV DNA using PCR-based techniques. 74.5 % of samples contained HPV DNA. 61.8 % of cases showed T2 and T3 staging. There were no differences in the frequencies of GSTT1/GSTM1 genotypes between HPV+ and HPV- cases (p>0.05). GSTT1^wt/GSTM^null patients were more likely to have higher TNM stages compared with other genotypes (p=0.012), but no differences were observed concerning perineural invasion nor lymphovascular invasion. These findings indicate that GSTT1 and GSTM1 deletions are common in HPV+ and HPV- penile cancers. GSTM1 deletions in the presence of wild-type GSTT1 seems to be associated with tumor progression, and additional studies are warranted to confirm its potential as a prognostic marker in penile cancer.

Keywords: Glutathione; HPV; Tobacco; Tumor staging.