Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

PRACTICAL consortium

doi:10.1158/1055-9965.epi-18-0079

Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

PRACTICAL consortium

Institut for Klinisk Medicin

6 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Vol/bind	28
Udgave nummer	1
Sider (fra-til)	208-216
Antal sider	9
ISSN	1055-9965
DOI	https://doi.org/10.1158/1055-9965.epi-18-0079
Status	Udgivet - jan. 2019

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10.1158/1055-9965.epi-18-0079

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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study. / PRACTICAL consortium.

I: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Bind 28, Nr. 1, 01.2019, s. 208-216.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{d399beeadf8b4f8e916bbed99aefb32a,

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 = "Adams, {Charleen D.} and Rebecca Richmond and Ferreira, {Diana L.Santos} 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 Nordestgaard, {B{\o}rge G.} and {PRACTICAL consortium}",

year = "2019",

month = jan,

doi = "10.1158/1055-9965.epi-18-0079",

language = "English",

volume = "28",

pages = "208--216",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "1",

}

TY - JOUR

T1 - Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

AU - Adams, Charleen D.

AU - Richmond, Rebecca

AU - Ferreira, Diana L.Santos

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 - Nordestgaard, Børge G.

AU - PRACTICAL consortium

PY - 2019/1

Y1 - 2019/1

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.

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

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

M3 - Journal article

C2 - 30352818

AN - SCOPUS:85059928972

SN - 1055-9965

VL - 28

SP - 208

EP - 216

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 1

ER -

Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study

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