Does Human JC Virus Play a Role in the International Variations and Temporal Trends of Early-Onset Colorectal Cancer? A Meta-Analysis

Abstract

The prevalence and incidence trend of early-onset colorectal cancer (EO-CRC) exhibit wide variations across the world, which could be attributed to early-life exposures such as diet and viral infections. We carried out a systematic review and meta-analysis to examine the association between John Cunningham virus (JCV) infection and EO-CRC. Literature was searched 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 time-weighted average annual per cent change in incidence rates of EO-CRC into rising-trend, stable-trend, and decreasing-trend settings. A total of 19 studies with 3065 participants were included. The meta-analysis showed that JCV increased the odds for colorectal adenoma development (6-fold) more than colorectal cancer (4.1-fold), in comparison to controls. 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 and matched adjacent colorectal tissues. 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 and matched adjacent colorectal tissues; no JCV DNA was detected in the decreasing-trend settings in both cancerous and non-cancerous colorectal tissues. These results suggest that JCV is likely involved in early stage of colorectal carcinogenesis, and may play a role in the international variations and temporal trends of EO-CRC in some parts of the world.