Epigenetic impact of infection on carcinogenesis: mechanisms and applications

Naoko Hattori, Toshikazu Ushijima

Viral and bacterial infections are involved in the development of human cancers, such as liver, nasopharyngeal, cervical, head and neck, and gastric cancers. Aberrant DNA methylation is frequently present in these cancers, and some of the aberrantly methylated genes are causally involved in cancer development and progression. Notably, aberrant DNA methylation can be present even in non-cancerous or precancerous tissues, and its levels correlate with the risk of cancer development, producing a so-called 'epigenetic field for cancerization'. Mechanistically, most viral or bacterial infections induce DNA methylation indirectly via chronic inflammation, but recent studies have indicated that some viruses have direct effects on the epigenetic machinery of host cells. From a translational viewpoint, a recent multicenter prospective cohort study demonstrated that assessment of the extent of alterations in DNA methylation in non-cancerous tissues can be used to predict cancer risk. Furthermore, suppression of aberrant DNA methylation was shown to be a useful strategy for cancer prevention in an animal model. Here, we review the involvement of aberrant DNA methylation in various types of infection-associated cancers, along with individual induction mechanisms, and we discuss the application of these findings for cancer prevention, diagnosis, and therapy.