Epidemiologic and epigenetic instruments to study mechanisms involved in prostate cancer relapse

Prostate Cancer (PC) is the most common cancer in elderly males (>70 years) in Europe, but also American and African populations are characterized by high incidence and mortality related to this malignancy. Incidence rates of PC became higher after the introduction of the Prostate Specific Antigen (PSA) screening. Actually, there isn’t a unique method to treat this pathology, so several therapeutic procedures could be used. The treatments frequently used are watchful waiting, prostatectomy and radiotherapy however often a pharmacological treatment is also used (in particular the anti-hormonal medications); sometimes two different options are used. The main aims of this study are the following: 1) Study the use of medications in patients with a diagnosis of PC in Friuli Venezia Giulia considering the period between 1998 and 2014. 2) Study the methylation status of a part of the Glutathione S-transferase Pi 1 (GSTP1) promoter in patients who underwent Radical Prostatectomy (RP) and try to understand if methylation of this promoter could influence the risk of relapse. 3) Study the features of patients who underwent Radical Prostatectomy, comparing those characterized by a relapse to those who are not characterized by a relapse. The first step has been the identification of subjects with a diagnosis of PC in Friuli Venezia Giulia (15079 cases) from Tumor’s register (data available from 1995 to 2009). In a second phase, subjects with only one tumor (PC) were selected (11521 people). Later, data on subjects, were crossed with data about medications (especially those related to prostatic problems) which were taken by these 2915 subjects. From data obtained, were selected those subjects underwent to Radical Prostatectomy (RP) (530 people) to whom was possible extract clinical information more detailed (TNM, Gleason score, PSA etc., obtaining 149 people). Finally, the last selection was based to the availability of biological samples (paraffin-embedded prostates specimens) on pathological anatomy, which were available for 122 patients. People selected were divided into people characterized by a disease relapse (PC) and subjects without a relapse (for whom no relapse was documented). The purpose of the two groups identified above was to understand if there were some differences in terms of methylation (related to the promoter of GSTP1), hence to determine whether this elements can influence the risk of relapse. During the studied period (from 1998 to 2014) in Friuli Venezia Giulia, the class of medications most used from patients with PC is that including Hormonal Preparations (HP), which shows a continuous increase, whereas the use of antiandrogens medications (AA) shows a decrease over time with the exception of new antiandrogens medications (belonging to the AAO class). The results show that people with higher levels of methylation have a higher risk of relapse, compared to those subjects with lower levels of methylation. Additionally, a higher Gleason score increases the risk of relapse, as shown in many papers in literature. The results obtained from Cox models shows that bivariate models (adjusted by age) are characterized by a trend of relapse’s risk, which increases with levels of methylation. This trend is not maintained in multiple models. In conclusion, the methylation of GSTP1 promoter might be useful to identify patients with higher risk of biochemical recurrence, however further studies based on an epidemiologic epigenetic approach are needed