Università degli studi di Modena e Reggio Emilia

There is evidence suggesting that the excretion and conversion of neutral sterols in the human large bowel might be somewhat related to the development of colorectal cancer. Therefore, our objectives were: to characterize the excretion and the major pattern of sterol degradation in normal conditions, both in children and in adults; and to investigate if abnormalities of these parameters are frequent in patients with colorectal cancer or polyps. The study has been carried out in: 38 adult volunteers; 29 children divided into 4 age groups; 22 patients with colorectal cancer; 16 members of 6 families with adenomatosis coli; 15 members of 2 families with a high prevalence of multiple polyps or cancer of the large bowel; 12 subjects with colorectal polyps without familiality. With the subjects kept under metabolic control, fecal samples were collected for at least 3 days and analyzed by thin layer chromatography and gas-liquid chromatography. Total neutral steroid excretion was lower in children than in adult volunteers; in contrast, there was no significant difference between the latter and the other investigated group of patients with cancer or polyps, with values ranging between 230 and 680 mg/day. All the adult volunteers were "high converters" of cholesterol to its intestinal metabolites coprostanol and coprostanone [89 +/- 10% (SE) of degradation]. Children less than 1 year old degraded little or no cholesterol (10.4 +/- 6% of total neutral sterols), whereas with increasing age the fraction of conversion became more similar to that of adults. In patients with colorectal tumors 2 populations could be defined, one characterized by a large degradation of cholesterol and the other by little or no conversion. Low degradation of cholesterol was found in 3 of 6 families with adenomatosis coli. In conclusion, we did not find any significant difference in total neutral sterol excretion among controls, colorectal cancer patients, or subjects at risk. In adult volunteers the normal pattern of cholesterol degradation is characterized by a large conversion of cholesterol to its intestinal metabolites. In children this process changes with increasing age from an absolute "nonconverter" state (after birth) to the pattern typical of adults. Finally, in a minority of patients with either polyps or cancer of the large bowel and of their first-degree relatives, cholesterol is poorly degraded and represents the most abundant fecal sterol.