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I started my research career to solve clinical problems about cancer which I had experienced as a physician. Although the molecular pathogenesis of cancer has been elucidated in terms of genetic aberrations due to revolutionized sequencing technology, it has been unclear what genetic events and molecular mechanisms are involved in normal tissues at the very early stage of carcinogenesis. Our studies on somatic mutations in the normal esophagus and colon have shown that even normal cells acquire somatic mutations through cell divisions necessary to maintain the homeostasis in multiple-cell organisms, that some mutated cells adapted to the surrounding environment are selected and expand, and that such expanded clones continue to remodel organs throughout life. Inspired by this point of view, we will perform genetic and epigenetic analysis on cells in organs affected by chronic diseases, including cancer, to elucidate evolutionary processes that cells follow, which might reflect the pathogenesis of chronic diseases. We hope that our study results will be exploited for future clinical practice.