A prospective study of serum bile acid concentrations and colorectal cancer risk in post-menopausal women on the island of Guernsey

Abstract

Secondary bile acids produced by the action of the colonic microflora may increase risk of colorectal cancer. Serum bile acid concentrations reflect the faecal bile acid profile and may be of value as biomarkers of risk of colorectal cancer. In a pilot investigation we examined: (i) the reproducibility of measurements of serum bile acids in two blood samples collected several years apart; and (ii) the hypothesis that relatively high levels of secondary bile acids, particularly deoxycholic acid, would be positively associated with an increased risk of colorectal cancer in a prospective study of 3680 women in Guernsey. There was poor reproducibility between repeat measurements of absolute serum concentrations of bile acids, but there was moderately good reproducibility for the ratios of serum concentrations of deoxycholic/cholic acid, lithocholic/chenodeoxycholic and secondary/primary bile acid concentrations (duplicate blood samples were available for 30 women). There were no significant differences in ratios of serum secondary to primary bile acids or in absolute concentrations of bile acids between the 46 women who developed colorectal cancer and their matched controls, although there was a suggestion that an increased risk was associated with a high ratio of deoxycholic/cholic acid (relative risk in top third compared to lower third=3.92 (95% CI 0.91-17.0, P for trend=0.096). These findings suggest that the ratios of serum bile acid concentrations are sufficiently reproducible for epidemiological studies, but that a larger study than our own is needed to adequately test the hypothesis of their relation to cancer risk.

Genetic Polymorphism in Cytochrome P450 7A1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study

“…Several case-control studies reported higher levels of secondary bile acids in the feces or sera in patients with colorectal cancer or adenomas as compared with those without these lesions (10-13), but the findings were not replicated in other studies (14)(15)(16). A prospective study reported a suggestive increase in the risk of colorectal cancer associated with a high ratio of serum deoxycholic to cholic acids (17). Another epidemiologic evidence is the increased risk of proximal colon cancer in individuals having the gallbladder removed (18,19).…”

Role of Bacteria in Oncogenesis

“…The studies with the strongest methodology (using age-matched controls screened for polyps and adjusting for cholecystectomy) report a positive association between secondary bile products and colon cancer (22,119). Prospective studies of colon cancer, however, have failed to confirm this association (53,97).…”

Genetic polymorphism of cholesterol 7α‐hydroxylase (CYP7A1) and colorectal adenomas: Self Defense Forces Health Study

“…(8)(9)(10)(11) A high ratio of serum deoxycholic acid to cholic acid tended to be associated with an increased risk of colorectal cancer in a prospective study. (12) Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme that converts cholesterol into cholesterol 7α-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis. (13) Overexpression of cholesterol 7α-hydroxylase activity in hamsters results in a dose-dependent decrease in plasma cholesterol concentrations.…”