Abstract
Exposure to radiation and chemicals, oncogenic viruses, microbiomes, and inflammation are the major events of cancer initiation. DNA damage and chromosomal aberrations are classically considered the main causes of cancer. The recent idea of epigenetics is broadening the concept, including the suggestion that oncogenic virus infection disrupts various intracellular signaling cascades. Chronic inflammation was proposed as the origin of cancer in the 19th century, and the molecular level of events has been made clear with scientific development. Much knowledge of cancer initiation has become available for integration into research. Simultaneously, the presence of cancer stem cells has been identified and characterized. However, the point of shift from normal to malignant still appears obscure even when taking cancer stem cells into consideration. From these points of view, the advent of cancer stem cells and cancer initiation are briefly discussed as the points of shift from normal to malignant in this paper.