Does human JC virus play a role in the international variations and temporal trends of early-onset colorectal cancer? A meta-analysis

Background: Several studies have investigated the possible role of John Cunningham virus (JCV) in colorectal carcinogenesis, however the results were conflicting. The aim of this meta-analysis was to examine the association between JCV and colorectal tumors with special reference to early-onset colorectal cancer (EO-CRC).Methods: A systematic search was conducted through the Embase, Cochrane Collaboration, and PubMed databases for studies comparing the presence of JCV DNA in colorectal cancerous and non-cancerous tissues. Countries where the studies were conducted were categorized into high and low prevalence settings for EO-CRC, and according to the incidence rates of EO-CRC into rising-trend, stable-trend, and decreasing-trend settings. The strength of association was estimated by Peto odds ratio and 95% confidence interval.Results: The meta-analysis showed that JCV increased the odds for colorectal cancer by 4.1-fold, and for colorectal adenoma by 6-fold in comparison to controls. Compared with adjacent and non-adjacent colorectal tissues, JCV increased the odds for colorectal cancer by 4-fold and 4.2-fold, and for colorectal adenoma by 6.6-fold and 5.6-fold, respectively. The odds for colorectal tumor development with JCV infection were significantly higher in the high-prevalence settings than in the low-prevalence settings when compared with controls (P = 0.01) and matched adjacent colorectal tissues (P = 0.0002). Similarly, the odds for colorectal tumor development trended to be higher in the rising-trend settings than in the stable-trend settings when compared with controls (P = 0.05); no JCV DNA was detected in the decreasing-trend settings in both cancerous and non-cancerous colorectal tissues. Conclusion: JCV infection is associated with increased risk of both colorectal cancer and adenoma, and is likely involved in early stage of carcinogenesis. The higher odds for colorectal tumor development in the high-prevalence and rising-trend settings for EO-CRC indicate that JCV may play a role in the international variations and temporal trends of EO-CRC in several parts of the world.