Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study

Abstract

Background Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Methods Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Results Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. Conclusions This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

Coffee and digestive cancers—what do we know, and where do we go?

“…A separate investigation, published in the same journal, identified an association between prediagnostic bile acid concentrations and colon cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 10 These observations are supported by experimental models demonstrating that bile acids are critical to the gut-liver-axis, and may contribute to the pathogenesis of liver, colorectal and perhaps other digestive diseases. 11 These exciting results provide plausible mechanisms linking coffee drinking to gastrointestinal cancer, and merit replication in future studies.…”

Identification of GSPT1 as prognostic biomarker and promoter of malignant colon cancer cell phenotypes via the GSK-3β/CyclinD1 pathway

“…The five-year survival rate at early diagnosis is 90%, and the incidence of distant metastasis is less than 10% [ 19 ]. Specific tumor biomarkers are urgently needed to help enable early diagnosis of colorectal cancer, selection of "personalized" treatment strategies, and to predict prognosis [ 20 – 22 ]. In the present study, we analyzed the sequencing data of colon cancer in the TCGA database and found that GSPT1 was abnormally highly expressed in colon cancer tissue and related to tumor size.…”

Blockage of Cholinergic Signaling via Muscarinic Acetylcholine Receptor 3 Inhibits Tumor Growth in Human Colorectal Adenocarcinoma

“…Nevertheless, our results are in line with the published in vivo data and add to the body of evidence that antagonizing M3R not only prevents de novo tumor formation but may indeed be a tool to treat CRC in a clinical setting. Finally, since bile acids present intraluminally promote CRC tumorigenesis, antagonizing bile acid-induced M3R activation may add to the benefit of darifenacin [38,39].…”