Citations 2
A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data
Huynh‐Le, Minh‐Phuong , Fan, Chun Chieh , Karunamuni, Roshan , Walsh, Eleanor , Turner, Emma L. , Gillatt, David , Martin, Richard M. , Neal, David E. , Donovan, Jenny , Parsons, J. Kellogg , Eeles, Rosalind A. , Easton, Douglas F. , Kote‐Jarai, Zsofia , Olama, Ali Amin Al , Garcia, Sara Benlloch, Grönberg, Henrik , Schleutker, Johanna , Tammela, Teuvo L.J. , Nordestgaard, Børge G. , Travis, Ruth C. , Pashayan, Nora , Thibodeau, Stephen N. , Schaid, Daniel J. , Maier, Christiane, Vogel, Walther , Luedeke, Manuel, Herkommer, Kathleen , Kibel, Adam S. , Wokołorczyk, Dominika , Kluźniak, Wojciech , Holleczek, Bernd , Sellers, Thomas A. , Slavov, Chavdar Kroumov, Kaneva, Radka , Mitev, Vanio , Batra, Jyotsna , Teixeira, Manuel R. , Paulo, Paula , Maia, Sofia , Pandha, Hardev , Mills, Ian G. , Dale, Anders M. , Seibert, Tyler M. , Lane, J. Athene , Walsh, Eleanor I , Lane, J Athene , Donovan, Jenny L , Eeles, Rosalind A , Amin Al Olama, Ali , Muir, Kenneth , Grönberg, Henrik , Wiklund, Fredrik E. , Schleutker, Johanna , Key, Tim , Travis, Ruth C , Pharoah, Paul D P , Pashayan, Nora , Herkommer, Kathleen , Cannon-Albright, Lisa A , Brenner, Hermann , Schöttker, Ben , Park, Jong Y , Lin, Hui-Yi , Spurdle, Amanda B , Teixeira, Manuel R , Michael, Agnieszka , Mills, Ian G , Seibert, Tyler M , Dale, Anders M , Martin, Richard M , Batra, Jyotsna , Hamdy, Freddie C. , Muir, Kenneth , Aly, Markus , Sipeky, Csilla , Pharoah, Paul D.P. , Khaw, Kay‐Tee , McDonnell, Shannon K. , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong Y. , Lin, Hui‐Yi , Clements, Judith A. , Spurdle, Amanda B. , Michael, Agnieszka , Andreassen, Ole A.
Cancer Epidemiology, Biomarkers & Prevention | June 24, 2020 | Volume: 29 | Issue: 9 | Pages: 1731-1738
Abstract Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3–T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.
Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
Adams, Charleen D. , Richmond, Rebecca C. , Ferreira, Diana L. Santos , Spiller, Wes , Tan, Vanessa Y. , Würtz, Peter , Donovan, Jenny , Hamdy, Freddie C. , Neal, David E. , Lane, J. Athene , Smith, George Davey , Relton, Caroline L. , Eeles, Rosalind A. , Haiman, Christopher A. , Schumacher, Fredrick R. , Olama, Ali Amin Al , Benlloch, Sara, Muir, Kenneth , Berndt, Sonja I., Conti, David V. , Gapstur, Susan M. , Stevens, Victoria L. , Batra, Jyotsna , Grönberg, Henrik , Pashayan, Nora , Schleutker, Johanna , West, Catharine , Mucci, Lorelei A. , Koutros, Stella , Sørensen, Karina D. , Mæhle, Lovise, Travis, Ruth C. , Rosenstein, Barry S. , Lu, Yong‐Jie , Kibel, Adam S. , Vega, Ana , Stanford, Janet L. , Nordestgaard, Børge G. , Maier, Christiane, Kim, Jeri , John, Esther M. , Teixeira, Manuel R. , Newcomb, Lisa F., Lessel, Davor , Kaneva, Radka , Usmani, Nawaid , Claessens, Frank , Townsend, Paul A. , Dominguez, Manuela Gago, Roobol, Monique J. , Ménégaux, F. , Pandha, Hardev , Thibodeau, Stephen N. , Martin, Richard M. , Teixeira, Manuel R , Vega, Ana , Eeles, Rosalind A , John, Esther M , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Lessel, Davor , Koutros, Stella , Martin, Richard M , Conti, David V , Batra, Jyotsna , Davey Smith, George , Zheng, Jie , Kote‐Jarai, Zsofia , Berndt, Sonja I. , Wiklund, Fredrik E. , Chanock, Stephen Jacob , Tangen, Catherine M. , Clements, Judith A. , Albanes, Demetrius , Wolk, Alicja , Cancel‐Tassin, Géraldine , Hamilton, Robert J , Ingles, Sue A. , Giles, Graham G. , Kogevinas, Manolis , Penney, Kathryn , Park, Jong Y. , Cybulski, Cezary , Brenner, Hermann , Neuhausen, Susan L. , Ruyck, Kim De , Razack, Azad Hassan Abdul , Khaw, Kay‐Tee , Cannon‐Albright, Lisa , Claessens, Frank
Cancer Epidemiology, Biomarkers & Prevention | October 23, 2018 | Volume: 28 | Issue: 1 | Pages: 208-216
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.