Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
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-...
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| Veröffentlicht in: | CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION 2019-01, Vol.28 (1), p.208-216 |
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| creator | Adams, Charleen D Richmond, Rebecca Ferreira, Diana L. Santos Spiller, Wes Tan, Vanessa Zheng, Jie Wurtz, Peter Donovan, Jenny Hamdy, Freddie Neal, David Lane, J. Athene Smith, George Davey Relton, Caroline Eeles, Rosalind A Haiman, Christopher A Kote-Jarai, Z.Sofia Schumacher, Fredrick R Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Berndt, Sonja I Conti, David V Wiklund, Fredrik Chanock, Stephen J Gapstur, Susan Stevens, Victoria L Tangen, Catherine M Batra, Jyotsna Clements, Judith A Gronberg, Henrik Pashayan, Nora Schleutker, Johanna Albanes, Demetrius Wolk, Alicja West, Catharine M.L Mucci, Lorelei A Cancel-Tassin, Geraldine Koutros, Stella Sorensen, Karina Dalsgaard Maehle, Lovise Travis, Ruth C Hamilton, Robert J Ingles, Sue Ann Rosenstein, Barry S Lu, Yong-Jie Giles, Graham G Kibel, Adam S Vega, Ana Kogevinas, Manolis Penney, Kathryn L Park, Jong Y Stanford, Janet L Cybulski, Cezary Nordestgaard, Borge G Brenner, Hermann Maier, Christiane Kim, Jeri John, Esther M Teixeira, Manuel R Neuhausen, Susan L De Ruyck, Kim Razack, Azad Newcomb, Lisa F Lessel, Davor Kaneva, Radka P Usmani, Nawaid Claessens, Frank Townsend, Paul A Dominguez, Manuela Gago Roobol, Monique J Menegaux, Florence Khaw, Kay-Tee Cannon-Albright, Lisa A Pandha, Hardev Thibodeau, Stephen N Martin, Richard M |
| description | 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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Santos ; Spiller, Wes ; Tan, Vanessa ; Zheng, Jie ; Wurtz, Peter ; Donovan, Jenny ; Hamdy, Freddie ; Neal, David ; Lane, J. Athene ; Smith, George Davey ; Relton, Caroline ; Eeles, Rosalind A ; Haiman, Christopher A ; Kote-Jarai, Z.Sofia ; Schumacher, Fredrick R ; Al Olama, Ali Amin ; Benlloch, Sara ; Muir, Kenneth ; Berndt, Sonja I ; Conti, David V ; Wiklund, Fredrik ; Chanock, Stephen J ; Gapstur, Susan ; Stevens, Victoria L ; Tangen, Catherine M ; Batra, Jyotsna ; Clements, Judith A ; Gronberg, Henrik ; Pashayan, Nora ; Schleutker, Johanna ; Albanes, Demetrius ; Wolk, Alicja ; West, Catharine M.L ; Mucci, Lorelei A ; Cancel-Tassin, Geraldine ; Koutros, Stella ; Sorensen, Karina Dalsgaard ; Maehle, Lovise ; Travis, Ruth C ; Hamilton, Robert J ; Ingles, Sue Ann ; Rosenstein, Barry S ; Lu, Yong-Jie ; Giles, Graham G ; Kibel, Adam S ; Vega, Ana ; Kogevinas, Manolis ; Penney, Kathryn L ; Park, Jong Y ; Stanford, Janet L ; Cybulski, Cezary ; Nordestgaard, Borge G ; Brenner, Hermann ; Maier, Christiane ; Kim, Jeri ; John, Esther M ; Teixeira, Manuel R ; Neuhausen, Susan L ; De Ruyck, Kim ; Razack, Azad ; Newcomb, Lisa F ; Lessel, Davor ; Kaneva, Radka P ; Usmani, Nawaid ; Claessens, Frank ; Townsend, Paul A ; Dominguez, Manuela Gago ; Roobol, Monique J ; Menegaux, Florence ; Khaw, Kay-Tee ; Cannon-Albright, Lisa A ; Pandha, Hardev ; Thibodeau, Stephen N ; Martin, Richard M</creator><creatorcontrib>Adams, Charleen D ; Richmond, Rebecca ; Ferreira, Diana L. Santos ; Spiller, Wes ; Tan, Vanessa ; Zheng, Jie ; Wurtz, Peter ; Donovan, Jenny ; Hamdy, Freddie ; Neal, David ; Lane, J. Athene ; Smith, George Davey ; Relton, Caroline ; Eeles, Rosalind A ; Haiman, Christopher A ; Kote-Jarai, Z.Sofia ; Schumacher, Fredrick R ; Al Olama, Ali Amin ; Benlloch, Sara ; Muir, Kenneth ; Berndt, Sonja I ; Conti, David V ; Wiklund, Fredrik ; Chanock, Stephen J ; Gapstur, Susan ; Stevens, Victoria L ; Tangen, Catherine M ; Batra, Jyotsna ; Clements, Judith A ; Gronberg, Henrik ; Pashayan, Nora ; Schleutker, Johanna ; Albanes, Demetrius ; Wolk, Alicja ; West, Catharine M.L ; Mucci, Lorelei A ; Cancel-Tassin, Geraldine ; Koutros, Stella ; Sorensen, Karina Dalsgaard ; Maehle, Lovise ; Travis, Ruth C ; Hamilton, Robert J ; Ingles, Sue Ann ; Rosenstein, Barry S ; Lu, Yong-Jie ; Giles, Graham G ; Kibel, Adam S ; Vega, Ana ; Kogevinas, Manolis ; Penney, Kathryn L ; Park, Jong Y ; Stanford, Janet L ; Cybulski, Cezary ; Nordestgaard, Borge G ; Brenner, Hermann ; Maier, Christiane ; Kim, Jeri ; John, Esther M ; Teixeira, Manuel R ; Neuhausen, Susan L ; De Ruyck, Kim ; Razack, Azad ; Newcomb, Lisa F ; Lessel, Davor ; Kaneva, Radka P ; Usmani, Nawaid ; Claessens, Frank ; Townsend, Paul A ; Dominguez, Manuela Gago ; Roobol, Monique J ; Menegaux, Florence ; Khaw, Kay-Tee ; Cannon-Albright, Lisa A ; Pandha, Hardev ; Thibodeau, Stephen N ; Martin, Richard M</creatorcontrib><description>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.</description><identifier>ISSN: 1055-9965</identifier><language>eng</language><publisher>AMER ASSOC CANCER RESEARCH</publisher><ispartof>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2019-01, Vol.28 (1), p.208-216</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,27839</link.rule.ids></links><search><creatorcontrib>Adams, Charleen D</creatorcontrib><creatorcontrib>Richmond, Rebecca</creatorcontrib><creatorcontrib>Ferreira, Diana L. Santos</creatorcontrib><creatorcontrib>Spiller, Wes</creatorcontrib><creatorcontrib>Tan, Vanessa</creatorcontrib><creatorcontrib>Zheng, Jie</creatorcontrib><creatorcontrib>Wurtz, Peter</creatorcontrib><creatorcontrib>Donovan, Jenny</creatorcontrib><creatorcontrib>Hamdy, Freddie</creatorcontrib><creatorcontrib>Neal, David</creatorcontrib><creatorcontrib>Lane, J. Athene</creatorcontrib><creatorcontrib>Smith, George Davey</creatorcontrib><creatorcontrib>Relton, Caroline</creatorcontrib><creatorcontrib>Eeles, Rosalind A</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><creatorcontrib>Kote-Jarai, Z.Sofia</creatorcontrib><creatorcontrib>Schumacher, Fredrick R</creatorcontrib><creatorcontrib>Al Olama, Ali Amin</creatorcontrib><creatorcontrib>Benlloch, Sara</creatorcontrib><creatorcontrib>Muir, Kenneth</creatorcontrib><creatorcontrib>Berndt, Sonja I</creatorcontrib><creatorcontrib>Conti, David V</creatorcontrib><creatorcontrib>Wiklund, Fredrik</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Gapstur, Susan</creatorcontrib><creatorcontrib>Stevens, Victoria L</creatorcontrib><creatorcontrib>Tangen, Catherine M</creatorcontrib><creatorcontrib>Batra, Jyotsna</creatorcontrib><creatorcontrib>Clements, Judith A</creatorcontrib><creatorcontrib>Gronberg, Henrik</creatorcontrib><creatorcontrib>Pashayan, Nora</creatorcontrib><creatorcontrib>Schleutker, Johanna</creatorcontrib><creatorcontrib>Albanes, Demetrius</creatorcontrib><creatorcontrib>Wolk, Alicja</creatorcontrib><creatorcontrib>West, Catharine M.L</creatorcontrib><creatorcontrib>Mucci, Lorelei A</creatorcontrib><creatorcontrib>Cancel-Tassin, Geraldine</creatorcontrib><creatorcontrib>Koutros, Stella</creatorcontrib><creatorcontrib>Sorensen, Karina Dalsgaard</creatorcontrib><creatorcontrib>Maehle, Lovise</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Hamilton, Robert J</creatorcontrib><creatorcontrib>Ingles, Sue Ann</creatorcontrib><creatorcontrib>Rosenstein, Barry S</creatorcontrib><creatorcontrib>Lu, Yong-Jie</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Kibel, Adam S</creatorcontrib><creatorcontrib>Vega, Ana</creatorcontrib><creatorcontrib>Kogevinas, Manolis</creatorcontrib><creatorcontrib>Penney, Kathryn L</creatorcontrib><creatorcontrib>Park, Jong Y</creatorcontrib><creatorcontrib>Stanford, Janet L</creatorcontrib><creatorcontrib>Cybulski, Cezary</creatorcontrib><creatorcontrib>Nordestgaard, Borge G</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Maier, Christiane</creatorcontrib><creatorcontrib>Kim, Jeri</creatorcontrib><creatorcontrib>John, Esther M</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Neuhausen, Susan L</creatorcontrib><creatorcontrib>De Ruyck, Kim</creatorcontrib><creatorcontrib>Razack, Azad</creatorcontrib><creatorcontrib>Newcomb, Lisa F</creatorcontrib><creatorcontrib>Lessel, Davor</creatorcontrib><creatorcontrib>Kaneva, Radka P</creatorcontrib><creatorcontrib>Usmani, Nawaid</creatorcontrib><creatorcontrib>Claessens, Frank</creatorcontrib><creatorcontrib>Townsend, Paul A</creatorcontrib><creatorcontrib>Dominguez, Manuela Gago</creatorcontrib><creatorcontrib>Roobol, Monique J</creatorcontrib><creatorcontrib>Menegaux, Florence</creatorcontrib><creatorcontrib>Khaw, Kay-Tee</creatorcontrib><creatorcontrib>Cannon-Albright, Lisa A</creatorcontrib><creatorcontrib>Pandha, Hardev</creatorcontrib><creatorcontrib>Thibodeau, Stephen N</creatorcontrib><creatorcontrib>Martin, Richard M</creatorcontrib><title>Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study</title><title>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</title><description>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.</description><issn>1055-9965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqVyr0KwjAUQOEMCtafd7ibgxRaY1q7WhUXQbCDW4nprcbWVJJb0bdXwQfQ6cDh6zAvDITwkyQSPdZ37hIEQZwI4bFDqq1qa0nanGCLJI9NrRUsdHOVtkLroClhryyi8ZdIqAgL2NnGkSSEVBqFFrQBOuNnv0EGe2qL55B1S1k7HH07YOP1Kks3ftXW2N7R5IW7SYV5OOUzEcXzJI84jwTn_8jJbzKnB_EX_y9PoQ</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Adams, Charleen D</creator><creator>Richmond, Rebecca</creator><creator>Ferreira, Diana L. Santos</creator><creator>Spiller, Wes</creator><creator>Tan, Vanessa</creator><creator>Zheng, Jie</creator><creator>Wurtz, Peter</creator><creator>Donovan, Jenny</creator><creator>Hamdy, Freddie</creator><creator>Neal, David</creator><creator>Lane, J. Athene</creator><creator>Smith, George Davey</creator><creator>Relton, Caroline</creator><creator>Eeles, Rosalind A</creator><creator>Haiman, Christopher A</creator><creator>Kote-Jarai, Z.Sofia</creator><creator>Schumacher, Fredrick R</creator><creator>Al Olama, Ali Amin</creator><creator>Benlloch, Sara</creator><creator>Muir, Kenneth</creator><creator>Berndt, Sonja I</creator><creator>Conti, David V</creator><creator>Wiklund, Fredrik</creator><creator>Chanock, Stephen J</creator><creator>Gapstur, Susan</creator><creator>Stevens, Victoria L</creator><creator>Tangen, Catherine M</creator><creator>Batra, Jyotsna</creator><creator>Clements, Judith A</creator><creator>Gronberg, Henrik</creator><creator>Pashayan, Nora</creator><creator>Schleutker, Johanna</creator><creator>Albanes, Demetrius</creator><creator>Wolk, Alicja</creator><creator>West, Catharine M.L</creator><creator>Mucci, Lorelei A</creator><creator>Cancel-Tassin, Geraldine</creator><creator>Koutros, Stella</creator><creator>Sorensen, Karina Dalsgaard</creator><creator>Maehle, Lovise</creator><creator>Travis, Ruth C</creator><creator>Hamilton, Robert J</creator><creator>Ingles, Sue Ann</creator><creator>Rosenstein, Barry S</creator><creator>Lu, Yong-Jie</creator><creator>Giles, Graham G</creator><creator>Kibel, Adam S</creator><creator>Vega, Ana</creator><creator>Kogevinas, Manolis</creator><creator>Penney, Kathryn L</creator><creator>Park, Jong Y</creator><creator>Stanford, Janet L</creator><creator>Cybulski, Cezary</creator><creator>Nordestgaard, Borge G</creator><creator>Brenner, Hermann</creator><creator>Maier, Christiane</creator><creator>Kim, Jeri</creator><creator>John, Esther M</creator><creator>Teixeira, Manuel R</creator><creator>Neuhausen, Susan L</creator><creator>De Ruyck, Kim</creator><creator>Razack, Azad</creator><creator>Newcomb, Lisa F</creator><creator>Lessel, Davor</creator><creator>Kaneva, Radka P</creator><creator>Usmani, Nawaid</creator><creator>Claessens, Frank</creator><creator>Townsend, Paul A</creator><creator>Dominguez, Manuela Gago</creator><creator>Roobol, Monique J</creator><creator>Menegaux, Florence</creator><creator>Khaw, Kay-Tee</creator><creator>Cannon-Albright, Lisa A</creator><creator>Pandha, Hardev</creator><creator>Thibodeau, Stephen N</creator><creator>Martin, Richard M</creator><general>AMER ASSOC CANCER RESEARCH</general><scope>FZOIL</scope></search><sort><creationdate>201901</creationdate><title>Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study</title><author>Adams, Charleen D ; Richmond, Rebecca ; Ferreira, Diana L. 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Santos</au><au>Spiller, Wes</au><au>Tan, Vanessa</au><au>Zheng, Jie</au><au>Wurtz, Peter</au><au>Donovan, Jenny</au><au>Hamdy, Freddie</au><au>Neal, David</au><au>Lane, J. Athene</au><au>Smith, George Davey</au><au>Relton, Caroline</au><au>Eeles, Rosalind A</au><au>Haiman, Christopher A</au><au>Kote-Jarai, Z.Sofia</au><au>Schumacher, Fredrick R</au><au>Al Olama, Ali Amin</au><au>Benlloch, Sara</au><au>Muir, Kenneth</au><au>Berndt, Sonja I</au><au>Conti, David V</au><au>Wiklund, Fredrik</au><au>Chanock, Stephen J</au><au>Gapstur, Susan</au><au>Stevens, Victoria L</au><au>Tangen, Catherine M</au><au>Batra, Jyotsna</au><au>Clements, Judith A</au><au>Gronberg, Henrik</au><au>Pashayan, Nora</au><au>Schleutker, Johanna</au><au>Albanes, Demetrius</au><au>Wolk, Alicja</au><au>West, Catharine M.L</au><au>Mucci, Lorelei A</au><au>Cancel-Tassin, Geraldine</au><au>Koutros, Stella</au><au>Sorensen, Karina Dalsgaard</au><au>Maehle, Lovise</au><au>Travis, Ruth C</au><au>Hamilton, Robert J</au><au>Ingles, Sue Ann</au><au>Rosenstein, Barry S</au><au>Lu, Yong-Jie</au><au>Giles, Graham G</au><au>Kibel, Adam S</au><au>Vega, Ana</au><au>Kogevinas, Manolis</au><au>Penney, Kathryn L</au><au>Park, Jong Y</au><au>Stanford, Janet L</au><au>Cybulski, Cezary</au><au>Nordestgaard, Borge G</au><au>Brenner, Hermann</au><au>Maier, Christiane</au><au>Kim, Jeri</au><au>John, Esther M</au><au>Teixeira, Manuel R</au><au>Neuhausen, Susan L</au><au>De Ruyck, Kim</au><au>Razack, Azad</au><au>Newcomb, Lisa F</au><au>Lessel, Davor</au><au>Kaneva, Radka P</au><au>Usmani, Nawaid</au><au>Claessens, Frank</au><au>Townsend, Paul A</au><au>Dominguez, Manuela Gago</au><au>Roobol, Monique J</au><au>Menegaux, Florence</au><au>Khaw, Kay-Tee</au><au>Cannon-Albright, Lisa A</au><au>Pandha, Hardev</au><au>Thibodeau, Stephen N</au><au>Martin, Richard M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study</atitle><jtitle>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</jtitle><date>2019-01</date><risdate>2019</risdate><volume>28</volume><issue>1</issue><spage>208</spage><epage>216</epage><pages>208-216</pages><issn>1055-9965</issn><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.</abstract><pub>AMER ASSOC CANCER RESEARCH</pub></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1055-9965 |
| ispartof | CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2019-01, Vol.28 (1), p.208-216 |
| issn | 1055-9965 |
| language | eng |
| recordid | cdi_kuleuven_dspace_123456789_633653 |
| source | Lirias (KU Leuven Association); American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| title | Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T12%3A25%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-kuleuven&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Circulating%20Metabolic%20Biomarkers%20of%20Screen-Detected%20Prostate%20Cancer%20in%20the%20ProtecT%20Study&rft.jtitle=CANCER%20EPIDEMIOLOGY%20BIOMARKERS%20&%20PREVENTION&rft.au=Adams,%20Charleen%20D&rft.date=2019-01&rft.volume=28&rft.issue=1&rft.spage=208&rft.epage=216&rft.pages=208-216&rft.issn=1055-9965&rft_id=info:doi/&rft_dat=%3Ckuleuven%3E123456789_633653%3C/kuleuven%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |