Do Transcribed Endogenous Retroviruses Predict Cancer Incidence?
Abstract
Endogenous retroviruses (ERVs) are genomic remnants of ancient retroviral infections, comprising a significant fraction of mammalian DNA. Reactivation and expression of ERVs have been observed in various human cancers[1], but it remains unclear whether baseline ERV activity contributes to cancer susceptibility across different species. Here we propose a novel comparative hypothesis: that mammalian species with a higher proportion of transcribed ERV sequences in adult somatic tissues will exhibit a higher lifetime incidence of cancer, whereas species with low baseline ERV expression will have lower cancer prevalence. We review background evidence supporting this idea – including known roles of ERVs in oncogenesis and cross-species differences in transposable element activity – and outline an interdisciplinary research approach to test the hypothesis. By integrating comparative genomics, transcriptomics, and oncology data, the study would quantify ERV expression across species and correlate it with documented cancer rates, controlling for confounders like body size and lifespan. We discuss how confirming this correlation could implicate ERV transcription as a novel evolutionary risk factor for cancer, reveal protective genomic mechanisms in species that suppress ERVs, and potentially identify new biomarkers or therapeutic targets in human cancer. This hypothesis bridges genomics and cancer biology, and its validation would encourage collaborative efforts across biology, bioinformatics, and medicine to further elucidate the role of “viral” genome elements in cancer risk.
