New pieces of the pathogenetic mosaic in inflammatory bowel disease

Ulcerative colitis is a lifelong disease with an elevated risk of colorectal neoplasia New hypotheses such as the defensin concept are available concerning the ongoing inflammatory reaction It is known that telomere length is related to neoplasia In this issue of EJGH it is speculated as to whether the telomere length of fibroblasts is related to the age of onset of chronic inflammatory bowel disease It is questionable whether the length of telomeres in fibroblasts is related directly to neoplasia but indirectly via variable age of onset and duration of disease Ulcerative colitis (UC) is a lifelong disease. Patients with UC have an approximately 20% risk of developing colorectal cancer. The risk of neoplasia increases with the duration of the disease. Why some patients develop colorectal cancer and others do not is still poorly understood. UC patients who develop cancer have an underlying process of genetic and epigenetic instability in the inflamed mucosa, as indicated previously using several experimental techniques. Rapid cell turnover and oxidative injury observed in UC mucosa is associated with accelerated telomere shortening, followed by an increased potential for the chromosomal ends to fuse, ending in chromatin damage and chromosomal instability. It has been reported that chromosomal losses are greater and telomeres are shorter in the biopsies of patients with long-standing UC. Telomere length is correlated with chromosomal instability in a variety of epithelial preneoplastic lesions. In the case of an inflammatory context for UC mucosa, this genetic (and also epigenetic) damage may be associated with cellular transformation and tumour progression. However, almost all studies have focussed on the hypothesis that the epithelial cells are the primary target in this scenario, leading to epithelial types of cancer. The elongated lifespan of fibroblasts, as reported in the paper by Getliffe et al. in this issue of European Journal of Gastroenterology and Hepatology, is probably indirectly connected to a lesser frequency of colorectal neoplasia in UC as part of a different immune response in these patients compared with individuals with early-onset UC.