Circulating metabolic biomarkers of screen-detected prostate cancer in the ProtecT study

PRACTICAL Consortium

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Original languageEnglish (US)
Pages (from-to)208-216
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2019

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Prostatic Neoplasms
Biomarkers
Random Allocation
Causality
Therapeutics
Genome-Wide Association Study
Cholesterol
Water-Electrolyte Balance
Metabolome
Cholesterol Esters
Information Storage and Retrieval
Prostate-Specific Antigen
Lipoproteins
Prostate
Phospholipids
Triglycerides
Fatty Acids
Genome
Lipids
Amino Acids

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Circulating metabolic biomarkers of screen-detected prostate cancer in the ProtecT study. / PRACTICAL Consortium.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 28, No. 1, 01.01.2019, p. 208-216.

Research output: Contribution to journalArticle

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title = "Circulating metabolic biomarkers of screen-detected prostate cancer in the ProtecT study",
abstract = "Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.",
author = "{PRACTICAL Consortium} and Adams, {Charleen D.} and Rebecca Richmond and {Santos Ferreira}, {Diana L.} and Wes Spiller and Vanessa Tan and Jie Zheng and Peter W{\"u}rtz and Jenny Donovan and Freddie Hamdy and David Neal and Lane, {J. Athene} and Smith, {George Davey} and Caroline Relton and Eeles, {Rosalind A.} and Haiman, {Christopher A.} and ZSofia Kote-Jarai and Schumacher, {Fredrick R.} and Olama, {Ali Amin Al} and Sara Benlloch and Kenneth Muir and Berndt, {Sonja I.} and Conti, {David V.} and Fredrik Wiklund and Chanock, {Stephen J.} and Susan Gapstur and Stevens, {Victoria L.} and Tangen, {Catherine M.} and Jyotsna Batra and Clements, {Judith A.} and Henrik Gronberg and Nora Pashayan and Johanna Schleutker and Demetrius Albanes and Alicja Wolk and West, {Catharine M.L.} and Mucci, {Lorelei A.} and G{\'e}raldine Cancel-Tassin and Stella Koutros and Sorensen, {Karina Dalsgaard} and Lovise Maehle and Travis, {Ruth C.} and Hamilton, {Robert J.} and Ingles, {Sue Ann} and Rosenstein, {Barry S.} and Lu, {Yong Jie} and Giles, {Graham G.} and Kibel, {Adam S.} and Ana Vega and Manolis Kogevinas and Thibodeau, {Stephen N}",
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T1 - Circulating metabolic biomarkers of screen-detected prostate cancer in the ProtecT study

AU - PRACTICAL Consortium

AU - Adams, Charleen D.

AU - Richmond, Rebecca

AU - Santos Ferreira, Diana L.

AU - Spiller, Wes

AU - Tan, Vanessa

AU - Zheng, Jie

AU - Würtz, Peter

AU - Donovan, Jenny

AU - Hamdy, Freddie

AU - Neal, David

AU - Lane, J. Athene

AU - Smith, George Davey

AU - Relton, Caroline

AU - Eeles, Rosalind A.

AU - Haiman, Christopher A.

AU - Kote-Jarai, ZSofia

AU - Schumacher, Fredrick R.

AU - Olama, Ali Amin Al

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Berndt, Sonja I.

AU - Conti, David V.

AU - Wiklund, Fredrik

AU - Chanock, Stephen J.

AU - Gapstur, Susan

AU - Stevens, Victoria L.

AU - Tangen, Catherine M.

AU - Batra, Jyotsna

AU - Clements, Judith A.

AU - Gronberg, Henrik

AU - Pashayan, Nora

AU - Schleutker, Johanna

AU - Albanes, Demetrius

AU - Wolk, Alicja

AU - West, Catharine M.L.

AU - Mucci, Lorelei A.

AU - Cancel-Tassin, Géraldine

AU - Koutros, Stella

AU - Sorensen, Karina Dalsgaard

AU - Maehle, Lovise

AU - Travis, Ruth C.

AU - Hamilton, Robert J.

AU - Ingles, Sue Ann

AU - Rosenstein, Barry S.

AU - Lu, Yong Jie

AU - Giles, Graham G.

AU - Kibel, Adam S.

AU - Vega, Ana

AU - Kogevinas, Manolis

AU - Thibodeau, Stephen N

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

AB - Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

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U2 - 10.1158/1055-9965.EPI-18-0079

DO - 10.1158/1055-9965.EPI-18-0079

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JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

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