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

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 - Penney, Kathryn L

AU - Park, Jong Y

AU - Stanford, Janet L

AU - Cybulski, Cezary

AU - Nordestgaard, Børge G

AU - Brenner, Hermann

AU - Maier, Christiane

AU - Kim, Jeri

AU - John, Esther M

AU - Teixeira, Manuel R

AU - Neuhausen, Susan L

AU - De Ruyck, Kim

AU - Razack, Azad

AU - Newcomb, Lisa F

AU - Lessel, Davor

AU - Kaneva, Radka P

AU - Usmani, Nawaid

AU - Claessens, Frank

AU - Townsend, Paul A

AU - Dominguez, Manuela Gago

AU - Roobol, Monique J

AU - Menegaux, Florence

AU - Khaw, Kay-Tee

AU - Cannon-Albright, Lisa A

AU - Pandha, Hardev

AU - Thibodeau, Stephen N

AU - Martin, Richard M

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 - SCORING: Journal article

C2 - 30352818

VL - 28

SP - 208

EP - 216

JO - CANCER EPIDEM BIOMAR

JF - CANCER EPIDEM BIOMAR

SN - 1055-9965

IS - 1

ER -