Serum bile acids and risk factors for colorectal cancer

Abstract

The ratio of deoxycholic acid to chenodeoxycholic acid in the serum of 62 men was inversely related to body mass index and to saturated fat intake after adjustment for body mass index, smoking, and age conversely, this ratio was associated positively with the intake of fibre from grains. Bile acids (BA) are potential risk factors for colorectal cancer (CRC). A small prospective study suggests that a high ratio of deoxycholic acid (DC) to cholic acid (CA) in serum is associated with an increased incidence of CRC (Costarelli et al, 2002). Based on a complete model of BA metabolism (Chaplin, 1998), it can be argued that the ratio of unconjugated DC to unconjugated chenodeoxycholic acid (CDC) in serum, in short the DC/CDC ratio, is relevant to CRC. Unconjugated DC in serum is regarded as being a biomarker for habitual colonic exposure to the cancerpromoting DC (Bayerdörffer et al, 1993), because the unconjugated BA is absorbed in the colon. The DC/CDC ratio may be a marker with high intraindividual reproducibility, because the colonic absorption of unconjugated DC is nearly equal to that of unconjugated CDC (Mekhjian et al, 1979) and the hepatic clearance of DC from the portal vein is equal to that of CDC (Ahlberg et al, 1977). The only difference between the variation of DC and that of CDC can be attributed to the dehydroxylation of the primary bile acid cholic acid (CA) to the secondary bile acid DC. The formation of CA, unlike that of CDC, is regulated by the amount of BA returning to the liver. If less unconjugated DC is returned, relatively more CA will be formed and the DC/CDC ratio in serum will be higher.We studied the relation between the DC/CDC ratio in serum and such CRC-promoting (dietary) factors as intake of energy, saturated fat, fibre, calcium, smoking and body mass index (Giovannucci, 2003). MATERIALS AND METHODSNonfasting blood specimens were collected from 121 men and women in the range of 20 -60 years old, who participated in the validation study of the Dutch food frequency questionnaire for the European Prospective Investigation into Cancer and Nutrition (EPIC) . The samples of the 62 men, from which the blood was drawn more than 4 h after a meal, were selected for analysis of individual BA in the serum, as described before (Salemans et al, 1993). Only men were selected for logistic reasons. RESULTSThe characteristics of the study subjects, the dietary intakes of nutrients and the concentrations of total unconjugated BA in serum are shown in Table 1. Dietary fibre from sources other than fruits and vegetables was derived mainly from grains. In all, 25% of the men were current smokers.Saturated fat intake was inversely related to the log of serum DC/ CDC ratio univariately, as well as after adjustment for potential confounding factors like body mass index, smoking age and (Table 2). Also, calcium intake was inversely associated to the log of serum DC/CDC ratio in univariate analyses, but disappeared in the adjusted models. Conversely, for total dietary fibre, a positive relation was observed in t...

Bile acid distributions, sex-specificity, and prognosis in colorectal cancer

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Beyond cancer genes: colorectal cancer as robust intrinsic states formed by molecular interactions

“…CRC development may take years and involve multiple risk factors [3,[69][70][71]. Intermediate steps have been observed.…”

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