Dataset Information

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.

ABSTRACT:

Background

Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.

Methods

We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.

Results

Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.

Conclusions

These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

SUBMITTER: Breeur M

PROVIDER: S-EPMC9580145 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.

Breeur Marie M Ferrari Pietro P Dossus Laure L Jenab Mazda M Johansson Mattias M Rinaldi Sabina S Travis Ruth C RC His Mathilde M Key Tim J TJ Schmidt Julie A JA Overvad Kim K Tjønneland Anne A Kyrø Cecilie C Rothwell Joseph A JA Laouali Nasser N Severi Gianluca G Kaaks Rudolf R Katzke Verena V Schulze Matthias B MB Eichelmann Fabian F Palli Domenico D Grioni Sara S Panico Salvatore S Tumino Rosario R Sacerdote Carlotta C Bueno-de-Mesquita Bas B Olsen Karina Standahl KS Sandanger Torkjel Manning TM Nøst Therese Haugdahl TH Quirós J Ramón JR Bonet Catalina C Barranco Miguel Rodríguez MR Chirlaque María-Dolores MD Ardanaz Eva E Sandsveden Malte M Manjer Jonas J Vidman Linda L Rentoft Matilda M Muller David D Tsilidis Kostas K Heath Alicia K AK Keun Hector H Adamski Jerzy J Keski-Rahkonen Pekka P Scalbert Augustin A Gunter Marc J MJ Viallon Vivian V

BMC medicine 20221019 1

<h4>Background</h4>Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.<h4>Methods</h4>We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies ...[more]

PMID: 36258205

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Project description:BackgroundLittle is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer.MethodsIn a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure.ResultsSeven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p?<?0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD)?=?0.73; 95% confidence interval (CI) 0.62-0.86; p trend?=?0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD?=?0.54; 95% CI 0.40-0.72; p trend?=?0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4.ConclusionsSeveral metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.

Dataset Information

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.

Background

Methods

Results

Conclusions

Publications

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.

Similar Datasets

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