Studies in literature suggest that some human viruses, including JC polyomavirus (JCV), 1-3 human cytomegalovirus (HCMV), 4 human papillomaviruses (HPVs), and Epstein-Barr virus (EBV), 9,10 have a pathogenic role in starting or promoting colorectal cancer. However, a revision of the literature indicates that this association between colorectal tumors and viral infection is still matter of debate and further studies using robust methods to detect viral infection are required. In fact, the prevalence of viral infection in colorectal cancer samples varies widely among series, and this variability appears to be mainly related to technical aspects, such as in the case of JCV, for which the prevalence in colorectal tumors has been reported to range from 0 11 to 90% in different studies.
In our study, we used sensitive quantitative real-time PCR analysis and PCR and sequencing to investigate the prevalence of genome sequences not only of JCV, but also of other polyomaviruses which have been involved in human infection, i.e., BK virus (BKV), Simian virus 40 (SV40), and the newly discovered Washington University polyomavirus (WUV), Karolinska Institute polyomavirus (KIV) and Merkel cell carcinoma polyomavirus (MCV), 17 in a large series of colorectal adenocarcinomas, adenomas and normal mucosa samples. Moreover, in the same samples, we investigated the presence DNA sequences of the herpesviruses HCMV and EBV and HPVs, which have been also suggested to be associated with colorectal tumorigenesis. A detailed description of methods is reported in the supporting information table. Patients gave informed consent to the study, which was approved by the local ethics committee and performed according to Declaration of Helsinki guidelines.
Originally, the aim of our study was to investigate the prevalence of JCV infection in colorectal cancers from different age groups. To this aim, we first analyzed 144 archival samples of formalin-fixed paraffin-embedded tissues (group 1, Table ), collected at the Department of Medical Diagnostic Sciences and Special Therapies of the University of Padova in the period ranging from 1998 to 2007. Group 1 included colorectal adenocarcinomas and adjacent mucosa, from 72 patients, who were selected on the basis of age (36 patients were 45 years, age range 32-45 years; 36 patients were 75 years, age range 75-89 years) and matched for gender (14 males and 22 females in both subgroups), tumor site (28 in sigmoid, 30 in ascendent, 11 in descendent, and 3 in rectal colon in both subgroups), and stage (11 stage I-II, 17 stage III, 8 stage 4 in both subgroups). Quite unexpectedly, all samples of group 1 tested negative for Additional Supporting Information may be found in the online version of this article.
Grant sponsor: AIRC (Associazione Italiana per la Ricerca sul Cancro).