The influence of age on colonic epithelial cell proliferation

Abstract

Cancer of the large bowel is relatively rare in persons younger than 50 years of age, but its incidence increases sharply in persons older than 60 years of age. We thought that the evaluation of colonic cell proliferation, an accurate biomarker of predisposition to colorectal cancer, might help to elucidate the susceptibility of elderly persons to this common malignancy. Accordingly, 30 persons with normal lower endoscopy results were divided into three age groups (30 to 50,51 to 65, and 66 to 90 years of age; Groups 1,2, and 3, respectively). Samples of rectal mucosa were taken at endoscopic examination, incubated with ['H]thymidine, and processed with standard autoradiographic techniques. At histologic examination, each intestinal hemicrypt was divided into five equal longitudinal compartments from the fundus (compartment 1) to the surface (compartment 5). The number and the position of labeled cells along the crypt were recorded. The total labeling index (LI) (the ratio of labeled cells to total cells) was significantly higher in Group 3 than in the two other groups. Similarly, the LI per crypt compartment in the most superficial portions of the crypts was consistently higher in persons older than 65 years of age (P < 0.01 at least), indicating an expansion of the proliferative zone to the most superficial portion of the colonic glands. When the proliferative profiles of the three groups of subjects investigated were compared with those of patients with polyps, an almost complete overlap of values was observed between this population at increased risk for cancer and the subjects in Group 3. We conclude that aging is characterized by an overall increase of epithelial cell proliferation in colorectal mucosa and by an upwards expansion of the proliferative compartment, similar to that observed in a population at risk for cancer of the large bowel. Cancer 622373-2377,1988. ESPITE the most recent technologic advances, cancer D of the large bowel is still a major cause of neoplastic morbidity and mortality.' As with all tumors of the digestive organs, colorectal cancer is relatively rare in persons younger than 50 years of age but shows a rapid increase in incidence in persons older than 60 years of age.2 Polyps of the large bowel, the natural precursors of ~ a n c e r , ~ show the same age-specific incidence. In addition, after their removal they tend to recur more frequently in elderly person^.^ The reasons why older persons are more susceptible to colorectal cancer are still unclear. Recently, however, many biologic indices or markers have been proposed to improve the identification of and surveillance on persons at risk for large bowel turn or^.^,^ Therefore, it Presented in part at the XXVI Meeting of the Italian Association of Gastroenterology, Sorrento, Italy, November 5-7, 1987. From the *CIstituto di Patologia Medica, the tlstituto di Radiologia, the 3Cattedra

A Descriptive Study of Colorectal Cancer in Hiwa Cancer Hospital, Sulaymaniyah, Iraq

“…The DNA damages certainly increases in with ageing, suggesting frequent stochastic cellular insults (Taylor et al, 2003). Aging also increases (rather than decreasing) epithelial proliferation in human colon (Roncucci et al, 1988). The incidence of CRC is uncommon under the age of 50 years especially sporadic CRC and continues to increase up to the age of 85 years (Holt et al, 2009).…”

CpG island methylator phenotype in colorectal cancer

“…By potentially affecting genes that regulate the growth and͞or differentiation of these cells, such methylation could account, in part, for the hyperproliferative state that is thought to precede tumor formation in the colon (38). Such hyperproliferation is known to arise with age in colorectal epithelium (39,40) and to be marked in patients with colorectal cancer. Furthermore, modulation of type A methylation may provide one possible explanation for the reduction in CRC tumorigenesis by reducing levels of DNA-methyltransferase (41).…”

Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging

“…Morphological and biochemical studies from this and other laboratories have demonstrated increased proliferation and decreased apoptosis in the gastric and colonic mucosa of Fischer-344 rats, events that are seen during the development and progression of carcinogenesis (10 -12, 16, 19, 28). Morphological studies of the colonic mucosa of human volunteers have further revealed that, whereas cell proliferation in young is confined to the lower two-thirds of the crypt, with aging there is a major shift from the base to the middle and upper third of the gland (25), a pattern commonly observed in colorectal cancer. These and other relevant observations have led us to suggest that aging predisposes the gastrointestinal tract to carcinogenesis (1,16).…”