The fields both of cancer prevention and epigenetics have matured to a point where their intersection deserves sustained attention. There now is strong evidence for an epigenetic component of early neoplasia, and data on the cancer preventive properties of epigenetic modulation are emerging. With preclinical proof of principle at hand, the challenge is to translate these epigenetic findings into testable clinical hypotheses.

Cancer epigenetics—referring to gene expression patterns that are stable, faithfully transmitted from parent cell to daughter cell after division, largely irreversible, and unrelated to genetic variation or mutations (1)—started as a field of research almost three decades ago with the observation that 5-methylcytosine levels are lower in cancer cells than in normal cells (2). Initially regarded as biological curiosities, epigenetic phenomena have drawn much interest recently because of their importance in determining cellular physiology [such as the stem cell versus committed (determined) cell state] and pathology (such as cancer). Over the past few years, the field has gained center stage in cancer biology through advances in our understanding of how epigenetic changes (perhaps more commonly than genetic changes) are involved in modulating functional pathways that are key to the neoplastic phenotype (3, 4) and by showing the clinical efficacy of targeting epigenetics for the treatment of cancer (5). Epigenetic mechanisms including promoter DNA methylation, histone modifications, and RNA interference are now better understood and relatively easily detected, contributing to the recent explosion of information on these processes. Epigenetic alterations often are involved in the earliest stages of tumor progression, usually precede neoplastic transformation, and have been shown to affect tumor formation even in genetic mouse models of carcinogenesis (6). Therefore, the real clinical home of cancer epigenetics may be prevention, where epigenetics potentially will have its greatest impact. Dedicated exclusively to cancer prevention, the exciting new journal Cancer Prevention Research provides an excellent home for fleshing out the role of epigenetics in early neoplasia and the practical steps for implementing an epigeneticbased cancer prevention strategy. Epigenetic alterations are promising biomarkers of cancer risk and early neoplasia (7). The next generation of epigenetic-alteration studies should address technical issues (the best methods and markers) and practical translational issues (including positive and ne-