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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.

SUBMITTER: Kuhn T

PROVIDER: S-EPMC7225675 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Kühn Tilman T Stepien Magdalena M López-Nogueroles Marina M Damms-Machado Antje A Sookthai Disorn D Johnson Theron T Roca Marta M Hüsing Anika A Maldonado Sandra González SG Cross Amanda J AJ Murphy Neil N Freisling Heinz H Rinaldi Sabina S Scalbert Augustin A Fedirko Veronika V Severi Gianluca G Boutron-Ruault Marie-Christine MC Mancini Francesca Romana FR Sowah Solomon A SA Boeing Heiner H Jakszyn Paula P Sánchez Maria J MJ Merino Susana S Colorado-Yohar Sandra S Barricarte Aurelio A Khaw Kay Tee KT Schmidt Julie A JA Perez-Cornago Aurora A Trichopoulou Antonia A Karakatsani Anna A Thriskos Paschalis P Palli Domenico D Agnoli Claudia C Tumino Rosario R Sacerdote Carlotta C Panico Salvatore S Bueno-de-Mesquita Bas B van Gils Carla H CH Heath Alicia K AK Gunter Marc J MJ Riboli Elio E Lahoz Agustín A Jenab Mazda M Kaaks Rudolf R

Journal of the National Cancer Institute 20200501 5

<h4>Background</h4>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.<h4>Methods</h4>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. ...[more]

PMID: 31435679

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Project description:Background & aimsPlasma bile acids (BAs) have been extensively studied as pathophysiological actors in non-alcoholic steatohepatitis (NASH). However, results from clinical studies are often complicated by the association of NASH with type 2 diabetes (T2D), obesity, and insulin resistance (IR). Here, we sought to dissect the relationship between NASH, T2D, and plasma BA levels in a large patient cohort.MethodsFour groups of patients from the Biological Atlas of Severe Obesity (ABOS) cohort (Clinical Trials number NCT01129297) were included based on the presence or absence of histologically evaluated NASH with or without coincident T2D. Patients were matched for BMI, homeostatic model assessment 2 (HOMA2)-assessed IR, glycated haemoglobin, age, and gender. To study the effect of IR and BMI on the association of plasma BA and NASH, patients from the HEPADIP study were included. In both cohorts, fasting plasma BA concentrations were measured.ResultsPlasma BA concentrations were higher in NASH compared with No-NASH patients both in T2D and NoT2D patients from the ABOS cohort. As we previously reported that plasma BA levels were unaltered in NASH patients of the HEPADIP cohort, we assessed the impact of BMI and IR on the association of NASH and BA on the combined BA datasets. Our results revealed that NASH-associated increases in plasma total cholic acid (CA) concentrations depend on the degree of HOMA2-assessed systemic IR, but not on β-cell function nor on BMI.ConclusionsPlasma BA concentrations are elevated only in those NASH patients exhibiting pronounced IR.Lay summaryNon-alcoholic steatohepatitis (NASH) is a progressive liver disease that frequently occurs in patients with obesity and type 2 diabetes. Reliable markers for the diagnosis of NASH are needed. Plasma bile acids have been proposed as NASH biomarkers. Herein, we found that plasma bile acids are only elevated in patients with NASH when significant insulin resistance is present, limiting their utility as NASH markers.

Project description:PurposeThe etiology of exfoliation glaucoma (XFG) is poorly understood. We aimed to identify a prediagnostic plasma metabolomic signature associated with XFG.MethodsWe conducted a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study. We collected blood samples in 1989-1990 (Nurses' Health Study) and 1993-1995 (Health Professionals Follow-up Study). We identified 205 incident XFG cases through 2016 (average time to diagnosis from blood draw = 11.8 years) who self-reported glaucoma and were confirmed as XFG cases with medical records. We profiled plasma metabolites using liquid chromatography-mass spectrometry. We evaluated 379 known metabolites (transformed for normality using probit scores) using multiple conditional logistic models. Metabolite set enrichment analysis was used to identify metabolite classes associated with XFG. To adjust for multiple comparisons, we used number of effective tests (NEF) and the false discovery rate (FDR).ResultsMean age of cases (n = 205) at diagnosis was 71 years; 85% were women and more than 99% were Caucasian; controls (n = 205) reported eye examinations as of the matched cases' index date. Thirty-three metabolites were nominally significantly associated with XFG (P < 0.05), and 4 metabolite classes were FDR-significantly associated. We observed positive associations for lysophosphatidylcholines (FDR = 0.02) and phosphatidylethanolamine plasmalogens (FDR = 0.004) and inverse associations for triacylglycerols (FDR < 0.0001) and steroids (FDR = 0.03). In particular, the multivariable-adjusted odds ratio with each 1 standard deviation higher plasma cortisone levels was 0.49 (95% confidence interval, 0.32-0.74; NEF = 0.05).ConclusionsIn plasma from a decade before diagnosis, lysophosphatidylcholines and phosphatidylethanolamine plasmalogens were positively associated and triacylglycerols and steroids (e.g., cortisone) were inversely associated with XFG risk.

Dataset Information

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

Publications

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

Similar Datasets

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