Older individuals appear to acquire mitotically older colorectal cancers

The incidence of many common cancers increases with ageing. The purpose of this study is to infer whether cancer mitotic ages (total numbers of divisions since the zygote) also increase with chronological age. Mitotic ages may be inferred by counting numbers of replication errors or neutral passenger changes. Methylation at certain CpG-rich sequences or 'tags' appears to be proportional to mitotic age, because age-related increases in tag methylation are observed in mitotic tissues such as the colon. Such passenger tag methylation was measured by bisulphite sequencing from 16 colorectal cancers from differently aged male individuals. Both normal colon and cancers exhibited significant age-related increases in tag methylation, but cancer methylation was significantly higher. Therefore, older individuals appear to have mitotically older colorectal cancers. Cell division per se may be an important mechanism underlying the increased incidence of colorectal cancer with ageing, because the neoplastic phase appears more commonly to start from mitotically older crypt stem cells. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.