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1. Cluster effect for SNP–SNP interaction pairs for predicting complex traits

Author: Lin, Hui-Yi, Mazumder, Harun, Sarkar, Indrani, Huang, Po-Yu, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth R., Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Neal, David E., Nielsen, Sune F., Nordestgaard, Børge G., Grönberg, Henrik, Wiklund, Fredrik, MacInnis, Robert J., Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Kibel, Adam S., Cybulski, Cezary, Khaw, Kay-Tee, Maier, Christiane, Thibodeau, Stephen N., Teixeira, Manuel R., Cannon-Albright, Lisa, Brenner, Hermann, Kaneva, Radka, Pandha, Hardev, and Park, Jong Y.
Published: 2024
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2. Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Author: Fonseca, Nicolette M., Maurice-Dror, Corinne, Herberts, Cameron, Tu, Wilson, Fan, William, Murtha, Andrew J., Kollmannsberger, Catarina, Kwan, Edmond M., Parekh, Karan, Schönlau, Elena, Bernales, Cecily Q., Donnellan, Gráinne, Ng, Sarah W. S., Sumiyoshi, Takayuki, Vergidis, Joanna, Noonan, Krista, Finch, Daygen L., Zulfiqar, Muhammad, Miller, Stacy, Parimi, Sunil, Lavoie, Jean-Michel, Hardy, Edward, Soleimani, Maryam, Nappi, Lucia, Eigl, Bernhard J., Kollmannsberger, Christian, Taavitsainen, Sinja, Nykter, Matti, Tolmeijer, Sofie H., Boerrigter, Emmy, Mehra, Niven, van Erp, Nielka P., De Laere, Bram, Lindberg, Johan, Grönberg, Henrik, Khalaf, Daniel J., Annala, Matti, Chi, Kim N., and Wyatt, Alexander W.
Published: 2024
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3. Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score

Author: Huynh-Le, Minh-Phuong, Karunamuni, Roshan, Fan, Chun Chieh, Asona, Lui, Thompson, Wesley K, Martinez, Maria Elena, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth R, Lophatananon, Artitaya, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E, Nordestgaard, Børge G, Tangen, Catherine M, MacInnis, Robert J, Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A, Travis, Ruth C, Blot, William J, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Nielsen, Sune F, Kibel, Adam S, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Rosenstein, Barry S, Lu, Yong-Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L, Huff, Chad D, Teixeira, Manuel R, Multigner, Luc, Leach, Robin J, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, De Ruyck, Kim, Ost, Piet, Razack, Azad, Newcomb, Lisa F, Fowke, Jay H, Gamulin, Marija, Abraham, Aswin, Claessens, Frank, Castelao, Jose Esteban, Townsend, Paul A, Crawford, Dana C, Petrovics, Gyorgy, van Schaik, Ron HN, Parent, Marie-Élise, Hu, Jennifer J, Zheng, Wei, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, and Seibert, Tyler M
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Urologic Diseases, Prevention, Genetics, Good Health and Well Being, Male, Humans, Prostate-Specific Antigen, Prostatic Neoplasms, Early Detection of Cancer, Polymorphism, Single Nucleotide, Risk Factors, Risk Assessment, Genetic Predisposition to Disease, UKGPCS collaborators, APCB, NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis
Abstract: BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.
Published: 2022

4. Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge

Author: Bulten, Wouter, Kartasalo, Kimmo, Chen, Po-Hsuan Cameron, Ström, Peter, Pinckaers, Hans, Nagpal, Kunal, Cai, Yuannan, Steiner, David F, van Boven, Hester, Vink, Robert, Hulsbergen-van de Kaa, Christina, van der Laak, Jeroen, Amin, Mahul B, Evans, Andrew J, van der Kwast, Theodorus, Allan, Robert, Humphrey, Peter A, Grönberg, Henrik, Samaratunga, Hemamali, Delahunt, Brett, Tsuzuki, Toyonori, Häkkinen, Tomi, Egevad, Lars, Demkin, Maggie, Dane, Sohier, Tan, Fraser, Valkonen, Masi, Corrado, Greg S, Peng, Lily, Mermel, Craig H, Ruusuvuori, Pekka, Litjens, Geert, and Eklund, Martin
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Urologic Diseases, Prostate Cancer, Algorithms, Biopsy, Cohort Studies, Humans, Male, Neoplasm Grading, Prostatic Neoplasms, Reproducibility of Results, PANDA challenge consortium, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract: Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted κ, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.
Published: 2022

5. Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.

Author: Karunamuni, Roshan A, Huynh-Le, Minh-Phuong, Fan, Chun C, Thompson, Wesley, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, Lophatananon, Artitaya, UKGPCS collaborators, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, APCB BioResource (Australian Prostate Cancer BioResource), Grönberg, Henrik, Walsh, Eleanor I, Turner, Emma L, Lane, Athene, Martin, Richard M, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Nordestgaard, Børge G, Tangen, Catherine M, MacInnis, Robert J, Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A, Travis, Ruth C, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Nielsen, Sune F, Kibel, Adam S, Wiklund, Fredrik, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Rosenstein, Barry S, Vega, Ana, IMPACT Study Steering Committee and Collaborators, Kogevinas, Manolis, Penney, Kathryn L, Teixeira, Manuel R, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, Razack, Azad, Newcomb, Lisa F, Canary PASS Investigators, Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A, Roobol, Monique J, Zheng, Wei, Profile Study Steering Committee, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, and PRACTICAL Consortium
Subjects: UKGPCS collaborators, APCB BioResource, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Prevention, Urologic Diseases, Cancer, Prostate Cancer, Aging, Urology & Nephrology, Oncology and Carcinogenesis
Abstract: BackgroundPolygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).Materials and method180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.Results166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.ConclusionsIncorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.
Published: 2021

6. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Author: Huynh-Le, Minh-Phuong, Fan, Chun Chieh, Karunamuni, Roshan, Thompson, Wesley K, Martinez, Maria Elena, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nielsen, Sune F, Nordestgaard, Børge G, Wiklund, Fredrik, Tangen, Catherine M, Giles, Graham G, Wolk, Alicja, Albanes, Demetrius, Travis, Ruth C, Blot, William J, Zheng, Wei, Sanderson, Maureen, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Kibel, Adam S, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Khaw, Kay-Tee, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Thibodeau, Stephen N, Rosenstein, Barry S, Lu, Yong-Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L, Huff, Chad, Teixeira, Manuel R, Multigner, Luc, Leach, Robin J, Cannon-Albright, Lisa, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, De Ruyck, Kim, Pandha, Hardev, Razack, Azad, Newcomb, Lisa F, Fowke, Jay H, Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A, Bush, William S, Roobol, Monique J, Parent, Marie-Élise, Hu, Jennifer J, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, UKGPCS collaborators, APCB (Australian Prostate Cancer BioResource), NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, and PRACTICAL Consortium
Subjects: UKGPCS collaborators, APCB, NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Humans, Prostatic Neoplasms, Neoplasm Invasiveness, Multivariate Analysis, Multifactorial Inheritance, Aged, Middle Aged, Ethnic Groups, Male, Self Report, Aging, Urologic Diseases, Cancer, Prostate Cancer
Abstract: Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p
Published: 2021

7. A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

Author: Huynh-Le, Minh-Phuong, Fan, Chun Chieh, Karunamuni, Roshan, Walsh, Eleanor I, Turner, Emma L, Lane, J Athene, Martin, Richard M, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Parsons, J Kellogg, Eeles, Rosalind A, Easton, Douglas F, Kote-Jarai, Zsofia, Al Olama, Ali Amin, Garcia, Sara Benlloch, Muir, Kenneth, Grönberg, Henrik, Wiklund, Fredrik, Aly, Markus, Schleutker, Johanna, Sipeky, Csilla, Tammela, Teuvo LJ, Nordestgaard, Børge Grønne, Key, Timothy J, Travis, Ruth C, Pharoah, Paul DP, Pashayan, Nora, Khaw, Kay-Tee, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S, Cybulski, Cezary, Wokolorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa A, Brenner, Hermann, Schöttker, Ben, Holleczek, Bernd, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Slavov, Chavdar Kroumov, Kaneva, Radka P, Mitev, Vanio I, Batra, Jyotsna, Clements, Judith A, Spurdle, Amanda B, BioResource, for the Australian Prostate Cancer, Teixeira, Manuel R, Paulo, Paula, Maia, Sofia, Pandha, Hardev, Michael, Agnieszka, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, and Consortium, for the PRACTICAL
Subjects: Biomedical and Clinical Sciences, Health Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Prevention, Urologic Diseases, Good Health and Well Being, Aged, Early Detection of Cancer, Humans, Male, Middle Aged, Neoplasm Grading, Population Control, Prostatic Neoplasms, Australian Prostate Cancer BioResource, PRACTICAL Consortium, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundA 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.MethodsUnited 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.ResultsThe 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.ConclusionsPHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.ImpactPersonalized genetic risk assessments could inform prostate cancer screening decisions.
Published: 2020

8. Prostate Cancer Incidence and Mortality in Men Exposed to α1-Adrenoceptor Antagonists

Author: Björnebo, Lars, primary, Razdan, Shirin, additional, Discacciati, Andrea, additional, Palsdottir, Thorgerdur, additional, Aly, Markus, additional, Nordström, Tobias, additional, Eklund, Martin, additional, Lundon, Dara, additional, Grönberg, Henrik, additional, Tewari, Ash, additional, Wiklund, Peter, additional, Kyprianou, Natasha, additional, and Lantz, Anna, additional
Published: 2024
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9. PD29-12 THE IMPACT OF THE TIME ELAPSED BETWEEN PRIMARY TREATMENT AND BCR ON CANCER SPECIFIC MORTALITY IN PATIENTS WHO EXPERIENCED BCR AFTER PRIMARY TREATMENT

Author: Pellegrino, Francesco, primary, Falagario, Ugo G., additional, Abbadi, Ahmad, additional, Björnebo, Lars, additional, Valdman, Alexander, additional, Carrieri, Giuseppe, additional, Briganti, Alberto, additional, Montorsi, Francesco, additional, Akre, Olof, additional, Aly, Markus, additional, Eklund, Martin, additional, Nordström, Tobias, additional, Grönberg, Henrik, additional, Lantz, Anna, additional, and Wiklund, Peter, additional
Published: 2024
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10. Long‐term oncological outcomes after multimodal treatment for locally advanced prostate cancer.

Author: Roldan, Fiorella L., Falagario, Ugo Giovanni, Olsson, Mats, Salas, Rodolfo Sánchez, Aly, Markus, Egevad, Lars, Lantz, Anna, Grönberg, Henrik, Akre, Olof, Hosseini, Abolfazl, and Wiklund, N. Peter
Published: 2024
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11. Prostate cancer incidence and mortality in men exposed to α1-adrenergic receptor antagonists.

Author: Björnebo, Lars, Razdan, Shirin, Discacciati, Andrea, Palsdottir, Thorgerdur, Aly, Markus, Nordström, Tobias, Eklund, Martin, Lundon, Dara, Grönberg, Henrik, Tewari, Ash, Wiklund, Peter, Kyprianou, Natasha, and Lantz, Anna
Subjects: PROSTATE-specific antigen, STATISTICAL models, PROPORTIONAL hazards models, BENIGN prostatic hyperplasia, PROSTATE cancer patients, PROSTATE cancer
Abstract: Background α1-Adrenergic receptor antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest that they induce cell death and inhibit tumor growth. This study evaluated the risk of prostate cancer death in men using α1-adrenergic receptor antagonists. Methods A population-based cohort study in Stockholm, Sweden (January 1, 2007, to December 31, 2019) included 451 779 men with a prostate-specific antigen test result. Study entry was 1 year after the first prostate-specific antigen test. Men were considered exposed at their second filled prescription. The primary outcome was prostate cancer mortality. Secondary outcomes were all-cause mortality and prostate cancer incidence. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all outcomes. Inverse-probability weighting with marginal structural models accounted for time-dependent confounders. Results Of 351 297 men in the final cohort, 39 856 (11.3%) were exposed to α1-adrenergic receptor antagonists. Median (interquartile range) follow-up for prostate cancer mortality was 8.9 (5.1-10.9) years; median (interquartile range) exposure time to α1-adrenergic receptor antagonists was 4.4 (2.0-7.6) years. There was no evidence of an association between α1-adrenergic receptor antagonist use and prostate cancer mortality, all-cause mortality, or high-grade prostate cancer. α1-Adrenergic receptor antagonist use was associated with an increased risk of prostate cancer (HR = 1.11, 95% CI = 1.06 to 1.17) and low-grade prostate cancer (HR = 1.22, 95% CI = 1.11 to 1.33). Men whose prostate cancer was treated with α1-adrenergic receptor antagonists underwent more frequent prostate-specific antigen testing. Conclusions Our findings show no significant association between α1-adrenergic receptor adrenoceptor antagonist exposure and prostate cancer mortality or high-grade prostate cancer. Although the preclinical evidence indicates a potential chemopreventive effect, this study's findings do not support it. [ABSTRACT FROM AUTHOR]
Published: 2024
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12. Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

Author: Seibert, Tyler M, Fan, Chun Chieh, Wang, Yunpeng, Zuber, Verena, Karunamuni, Roshan, Parsons, J Kellogg, Eeles, Rosalind A, Easton, Douglas F, Kote-Jarai, ZSofia, Al Olama, Ali Amin, Garcia, Sara Benlloch, Muir, Kenneth, Grönberg, Henrik, Wiklund, Fredrik, Aly, Markus, Schleutker, Johanna, Sipeky, Csilla, Tammela, Teuvo Lj, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bisbjerg, Rasmus, Røder, M Andreas, Iversen, Peter, Key, Tim J, Travis, Ruth C, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Pharoah, Paul, Pashayan, Nora, Khaw, Kay-Tee, Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S, Cybulski, Cezary, Wokolorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa, Brenner, Hermann, Cuk, Katarina, Saum, Kai-Uwe, Park, Jong Y, Sellers, Thomas A, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Batra, Jyotsna, Clements, Judith A, Spurdle, Amanda, Teixeira, Manuel R, Paulo, Paula, Maia, Sofia, Pandha, Hardev, Michael, Agnieszka, Kierzek, Andrzej, Karow, David S, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, and PRACTICAL Consortium*
Subjects: PRACTICAL Consortium*, Humans, Prostatic Neoplasms, Kallikreins, Prostate-Specific Antigen, Disease-Free Survival, Risk Assessment, Survival Analysis, Cohort Studies, Predictive Value of Tests, Age of Onset, Genotype, Polymorphism, Single Nucleotide, Aged, Middle Aged, European Continental Ancestry Group, Male, Early Detection of Cancer, Outcome Assessment, Health Care, Polymorphism, Single Nucleotide, Outcome Assessment, Health Care, Aging, Urologic Diseases, Cancer, Genetic Testing, Prevention, Prostate Cancer, Genetics, 2.1 Biological and endogenous factors, General & Internal Medicine, Public Health and Health Services, Clinical Sciences
Abstract: ObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.
Published: 2018

13. Prediagnostic Prostate-specific Antigen Testing and Clinical Characteristics in Men with Lethal Prostate Cancer

Author: Arvendell, Markus, primary, Björnebo, Lars, additional, Eklund, Martin, additional, Giovanni Falagario, Ugo, additional, Chandra Engel, Jan, additional, Akre, Olof, additional, Grönberg, Henrik, additional, Nordström, Tobias, additional, and Lantz, Anna, additional
Published: 2024
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14. The Capio Prostate Cancer Center Model for Prostate Cancer Diagnostics—Real-world Evidence from 2018 to 2022

Author: Palsdottir, Thorgerdur, primary, Söderbäck, Harald, additional, Jäderling, Fredrik, additional, Bergman, Martin, additional, Vigneswaran, Hari, additional, and Grönberg, Henrik, additional
Published: 2024
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15. Repeated Prostate Cancer Screening Using Prostate-Specific Antigen Testing and Magnetic Resonance Imaging

Author: Nordström, Tobias, primary, Annerstedt, Magnus, additional, Glaessgen, Axel, additional, Carlsson, Stefan, additional, Clements, Mark, additional, Abbadi, Ahmad, additional, Grönberg, Henrik, additional, Jäderling, Fredrik, additional, Eklund, Martin, additional, and Discacciati, Andrea, additional
Published: 2024
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16. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Author: Yarmolinsky, James, primary, Robinson, Jamie W., additional, Mariosa, Daniela, additional, Karhunen, Ville, additional, Huang, Jian, additional, Dimou, Niki, additional, Murphy, Neil, additional, Burrows, Kimberley, additional, Bouras, Emmanouil, additional, Smith-Byrne, Karl, additional, Lewis, Sarah J., additional, Galesloot, Tessel E., additional, Kiemeney, Lambertus A., additional, Vermeulen, Sita, additional, Martin, Paul, additional, Albanes, Demetrius, additional, Hou, Lifang, additional, Newcomb, Polly A., additional, White, Emily, additional, Wolk, Alicja, additional, Wu, Anna H., additional, Le Marchand, Loïc, additional, Phipps, Amanda I., additional, Buchanan, Daniel D., additional, Zhao, Sizheng Steven, additional, Gill, Dipender, additional, Chanock, Stephen J., additional, Purdue, Mark P., additional, Davey Smith, George, additional, Brennan, Paul, additional, Herzig, Karl-Heinz, additional, Järvelin, Marjo-Riitta, additional, Amos, Chris I., additional, Hung, Rayjean J., additional, Dehghan, Abbas, additional, Johansson, Mattias, additional, Gunter, Marc J., additional, Tsilidis, Kostas K., additional, Martin, Richard M., additional, Landi, Maria Teresa, additional, Stevens, Victoria, additional, Wang, Ying, additional, Albanes, Demetrios, additional, Caporaso, Neil, additional, Amos, Christopher I., additional, Shete, Sanjay, additional, Bickeböller, Heike, additional, Risch, Angela, additional, Houlston, Richard, additional, Lam, Stephen, additional, Tardon, Adonina, additional, Chen, Chu, additional, Bojesen, Stig E., additional, Wichmann, H-Erich, additional, Christiani, David, additional, Rennert, Gadi, additional, Arnold, Susanne, additional, Field, John K., additional, Le Marchand, Loic, additional, Melander, Olle, additional, Brunnström, Hans, additional, Liu, Geoffrey, additional, Andrew, Angeline, additional, Shen, Hongbing, additional, Zienolddiny, Shan, additional, Grankvist, Kjell, additional, Johansson, Mikael, additional, Teare, M. Dawn, additional, Hong, Yun-Chul, additional, Yuan, Jian-Min, additional, Lazarus, Philip, additional, Schabath, Matthew B., additional, Aldrich, Melinda C., additional, Eeles, Rosalind A., additional, Haiman, Christopher A., additional, Kote-Jarai, Zsofia, additional, Schumacher, Fredrick R., additional, Benlloch, Sara, additional, Al Olama, Ali Amin, additional, Muir, Kenneth R., additional, Berndt, Sonja I., additional, Conti, David V., additional, Wiklund, Fredrik, additional, Chanock, Stephen, additional, Tangen, Catherine M., additional, Batra, Jyotsna, additional, Clements, Judith A., additional, Grönberg, Henrik, additional, Pashayan, Nora, additional, Schleutker, Johanna, additional, Weinstein, Stephanie J., additional, West, Catharine M.L., additional, Mucci, Lorelei A., additional, Cancel-Tassin, Géraldine, additional, Koutros, Stella, additional, Sørensen, Karina Dalsgaard, additional, Grindedal, Eli Marie, additional, Neal, David E., additional, Hamdy, Freddie C., additional, Donovan, Jenny L., additional, Travis, Ruth C., additional, Hamilton, Robert J., additional, Ingles, Sue Ann, additional, Rosenstein, Barry S., additional, Lu, Yong-Jie, additional, Giles, Graham G., additional, MacInnis, Robert J., additional, Kibel, Adam S., additional, Vega, Ana, additional, Kogevinas, Manolis, additional, Penney, Kathryn L., additional, Park, Jong Y., additional, Stanfrod, Janet L., additional, Cybulski, Cezary, additional, Nordestgaard, Børge G., additional, Nielsen, Sune F., additional, Brenner, Hermann, additional, Maier, Christiane, additional, Logothetis, Christopher J., additional, John, Esther M., additional, Teixeira, Manuel R., additional, Neuhausen, Susan L., additional, De Ruyck, Kim, additional, Razack, Azad, additional, Newcomb, Lisa F., additional, Lessel, Davor, additional, Kaneva, Radka, additional, Usmani, Nawaid, additional, Claessens, Frank, additional, Townsend, Paul A., additional, Castelao, Jose Esteban, additional, Roobol, Monique J., additional, Menegaux, Florence, additional, Khaw, Kay-Tee, additional, Cannon-Albright, Lisa, additional, Pandha, Hardev, additional, Thibodeau, Stephen N., additional, Hunter, David J., additional, Kraft, Peter, additional, Blot, William J., additional, and Riboli, Elio, additional
Published: 2024
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17. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author: Adams, Lisa, Adlard, Julian, Alfonso, Rosa, Ali, Saira, Andrew, Angela, Araújo, Luís, Azam, Nazya, Ball, Darran, Barker, Queenstone, Basevitch, Alon, Benton, Barbara, Berlin, Cheryl, Bermingham, Nicola, Biller, Leah, Bloss, Angela, Bradford, Matilda, Bradshaw, Nicola, Branson, Amy, Brendler, Charles, Brennan, Maria, Bulman, Barbara, Burgess, Lucy, Cahill, Declan, Callard, Alice, Calvo Verges, Nuria, Cardoso, Marta, Carter, Vanda, Catanzaro, Mario, Chamberlain, Anthony, Chapman, Cyril, Chong, Michael, Clark, Caroline, Clowes, Virginia, Cogley, Lyn, Cole, Trevor, Compton, Cecilia, Conner, Tom, Cookson, Sandra, Cornford, Philip, Costello, Philandra, Coulier, Laura, Davies, Michaela, Dechet, Christopher, DeSouza, Bianca, Devlin, Gemma, Douglas, Fiona, Douglas, Emma, Dudakia, Darshna, Duncan, Alexis, Ellery, Natalie, Everest, Sarah, Freemantle, Sue, Frydenberg, Mark, Fuller, Debbie, Gabriel, Camila, Gale, Madeline, Garcia, Lynda, Gay, Simona, Genova, Elena, George, Angela, Georgiou, Demetra, Gisbert, Alexandra, Gleeson, Margaret, Glover, Wayne, Gnanapragasam, Vincent, Goff, Sally, Goldgar, David, Gonçalves, Nuno, Goodman, Selina, Gorrie, Jennifer, Gott, Hannah, Grant, Anna, Gray, Catherine, Griffiths, Julie, Gupwell, Karin, Gurasashvili, Jana, Hanslien, Eldbjørg, Haraldsdottir, Sigurdis, Hart, Rachel, Hartigan, Catherine, Hawkes, Lara, Heaton, Tricia, Henderson, Alex, Henrique, Rui, Hilario, Kathrine, Hill, Kathryn, Hulick, Peter, Hunt, Clare, Hutchings, Melanie, Ibitoye, Rita, Inglehearn, Thomas, Ireland, Joanna, Islam, Farah, Ismail, Siti, Jacobs, Chris, James, Denzil, Jenkins, Sharon, Jobson, Irene, Johnstone, Anne, Jones, Oliver, Josefsberg Ben-Yehoshua, Sagi, Kaemba, Beckie, Kaul, Karen, Kemp, Zoe, Kinsella, Netty, Klehm, Margaret, Kockelbergh, Roger, Kohut, Kelly, Kosicka-Slawinska, Monika, Kulkarni, Anjana, Kumar, Pardeep, Lam, Jimmy, LeButt, Mandy, Leibovici, Dan, Lim, Ramona, Limb, Lauren, Lomas, Claire, Longmuir, Mark, López, Consol, Magnani, Tiziana, Maia, Sofia, Maiden, Jessica, Male, Alison, Manalo, Merrie, Martin, Phoebe, McBride, Donna, McGuire, Michael, McMahon, Romayne, McNally, Claire, McVeigh, Terri, Melzer, Ehud, Mencias, Mark, Mercer, Catherine, Mitchell, Gillian, Mora, Josefina, Morton, Catherine, Moss, Cathryn, Murphy, Morgan, Murphy, Declan, Mzazi, Shumi, Nadolski, Maria, Newlin, Anna, Nogueira, Pedro, O'Keefe, Rachael, O'Toole, Karen, O'Connell, Shona, Ogden, Chris, Okoth, Linda, Oliveira, Jorge, Paez, Edgar, Palou, Joan, Park, Linda, Patel, Nafisa, Paulo Souto, João, Pearce, Allison, Peixoto, Ana, Perez, Kimberley, Petelin, Lara, Pichert, Gabriella, Poile, Charlotte, Potter, Alison, Preitner, Nadia, Purnell, Helen, Quinn, Ellen, Radice, Paolo, Rankin, Brigette, Rees, Katie, Renton, Caroline, Richardson, Kate, Risby, Peter, Rogers, Jason, Ruderman, Maggie, Ruiz, April, Sajoo, Anaar, Salvatore, Natale, Sands, Victoria, Sanguedolce, Francesco, Sattar, Ayisha, Saunders, Kathryn, Schofield, Lyn, Scott, Rodney, Searle, Anne, Sehra, Ravinder, Selkirk, Christina, Shackleton, Kylie, Shanley, Sue, Shaw, Adam, Shevrin, Daniel, Shipman, Hannah, Sidat, Zahirah, Siguake, Kas, Simon, Kate, Smyth, Courtney, Snadden, Lesley, Solanky, Nita, Solomons, Joyce, Sorrentino, Margherita, Stayner, Barbara, Stephenson, Robert, Stoffel, Elena, Thomas, Maggie, Thompson, Alan, Tidey, Lizzie, Tischkowitz, Marc, Torokwa, Audrey, Townshend, Sharron, Treherne, Katy, Tricker, Karen, Trinh, Quoc-Dien, Tripathi, Vishakha, Turnbull, Clare, Valdagni, Riccardo, Van As, Nicholas, Venne, Vickie, Verdon, Lizzie, Vitellaro, Marco, Vogel, Kristen, Walker, Lisa, Watford, Amy, Watt, Cathy, Weintroub, Ilana, Weiss, Shelly, Weissman, Scott, Weston, Michelle, Wiggins, Jennifer, Wise, Gillian, Woodhouse, Christopher, Yesildag, Pembe, Youngs, Alice, Yurgelun, Matthew, Zollo, Fabiana, Bancroft, Elizabeth K, Page, Elizabeth C, Brook, Mark N, Thomas, Sarah, Taylor, Natalie, Pope, Jennifer, McHugh, Jana, Jones, Ann-Britt, Karlsson, Questa, Merson, Susan, Ong, Kai Ren, Hoffman, Jonathan, Huber, Camilla, Maehle, Lovise, Grindedal, Eli Marie, Stormorken, Astrid, Evans, D Gareth, Rothwell, Jeanette, Lalloo, Fiona, Brady, Angela F, Bartlett, Marion, Snape, Katie, Hanson, Helen, James, Paul, McKinley, Joanne, Mascarenhas, Lyon, Syngal, Sapna, Ukaegbu, Chinedu, Side, Lucy, Thomas, Tessy, Barwell, Julian, Teixeira, Manuel R, Izatt, Louise, Suri, Mohnish, Macrae, Finlay A, Poplawski, Nicola, Chen-Shtoyerman, Rakefet, Ahmed, Munaza, Musgrave, Hannah, Nicolai, Nicola, Greenhalgh, Lynn, Brewer, Carole, Pachter, Nicholas, Spigelman, Allan D, Azzabi, Ashraf, Helfand, Brian T, Halliday, Dorothy, Buys, Saundra, Ramon y Cajal, Teresa, Donaldson, Alan, Cooney, Kathleen A, Harris, Marion, McGrath, John, Davidson, Rosemarie, Taylor, Amy, Cooke, Peter, Myhill, Kathryn, Hogben, Matthew, Aaronson, Neil K, Ardern-Jones, Audrey, Bangma, Chris H, Castro, Elena, Dearnaley, David, Dias, Alexander, Dudderidge, Tim, Eccles, Diana M, Green, Kate, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher S, Gronberg, Henrik, Hamdy, Freddie C, Johannsson, Oskar, Khoo, Vincent, Lilja, Hans, Lindeman, Geoffrey J, Lubinski, Jan, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita V, Moynihan, Clare, Ni Raghallaigh, Holly, Rennert, Gad, Collier, Rebecca, Offman, Judith, Kote-Jarai, Zsofia, and Eeles, Rosalind A
Published: 2021
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18. Prostate Cancer–specific and All-cause Mortality After Robot-assisted Radical Prostatectomy: 20 Years’ Report from the European Association of Urology Robotic Urology Section Scientific Working Group

Author: Falagario, Ugo Giovanni, Knipper, Sophie, Pellegrino, Francesco, Martini, Alberto, Akre, Olof, Egevad, Lars, Grönberg, Henrik, Moschovas, Marcio Covas, Bravi, Carlo Andrea, Tran, Joshua, Heiniger, Yasmin, von Kempis, Antonius, Schaffar, Robin, Carrieri, Giuseppe, Rochat, Charles-Henry, Mottrie, Alexandre, Ahlering, Thomas E., John, Hubert, Patel, Vipul, Graefen, Markus, and Wiklund, Peter
Abstract: In the present study, we reported the outcomes of patients with prostate cancer who underwent robot-assisted radical prostatectomy between 10 and 20 yr ago, and we found a very low probability of dying for prostate cancer in patients with low- and intermediate-risk disease. In contrast, high-risk patients face a significantly higher risk of prostate cancer mortality.
Published: 2024
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19. Biomarker discrimination and calibration with MRI-targeted biopsies: an analysis with the Stockholm3 test

Author: Vigneswaran, Hari T., Palsdottir, Thorgerdur, Olsson, Henrik, Haug, Erik S., Picker, Wolfgang, Löffeler, Sven, Grönberg, Henrik, Eklund, Martin, and Nordström, Tobias
Published: 2021
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20. Predictors of adverse pathology on radical prostatectomy specimen in men initially enrolled in active surveillance for low-risk prostate cancer

Author: Björnebo, Lars, Olsson, Henrik, Nordström, Tobias, Jäderling, Fredrik, Grönberg, Henrik, Eklund, Martin, and Lantz, Anna
Published: 2021
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21. Observational and genetic associations between cardiorespiratory fitness and cancer : a UK Biobank and international consortia study

Author: Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M. L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., 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, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., Brage, Soren, Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M. L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., 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, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., and Brage, Soren
Abstract: Background: The association of fitness with cancer risk is not clear. Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
Published: 2024
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22. Observational and genetic associations between cardiorespiratory fitness and cancer:a UK Biobank and international consortia study

Author: Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, Van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., 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, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., Brage, Soren, Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, Van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., 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, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., and Brage, Soren
Abstract: Background: The association of fitness with cancer risk is not clear. Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
Published: 2024

23. Ethnic variation in prostate cancer detection: a feasibility study for use of the Stockholm3 test in a multiethnic U.S. cohort

Author: Vigneswaran, Hari T., Discacciati, Andrea, Gann, Peter H., Grönberg, Henrik, Eklund, Martin, and Abern, Michael R.
Published: 2021
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24. Two susceptibility loci identified for prostate cancer aggressiveness.

Author: Berndt, Sonja I, Wang, Zhaoming, Yeager, Meredith, Alavanja, Michael C, Albanes, Demetrius, Amundadottir, Laufey, Andriole, Gerald, Beane Freeman, Laura, Campa, Daniele, Cancel-Tassin, Geraldine, Canzian, Federico, Cornu, Jean-Nicolas, Cussenot, Olivier, Diver, W Ryan, Gapstur, Susan M, Grönberg, Henrik, Haiman, Christopher A, Henderson, Brian, Hutchinson, Amy, Hunter, David J, Key, Timothy J, Kolb, Suzanne, Koutros, Stella, Kraft, Peter, Le Marchand, Loic, Lindström, Sara, Machiela, Mitchell J, Ostrander, Elaine A, Riboli, Elio, Schumacher, Fred, Siddiq, Afshan, Stanford, Janet L, Stevens, Victoria L, Travis, Ruth C, Tsilidis, Konstantinos K, Virtamo, Jarmo, Weinstein, Stephanie, Wilkund, Fredrik, Xu, Jianfeng, Lilly Zheng, S, Yu, Kai, Wheeler, William, Zhang, Han, African Ancestry Prostate Cancer GWAS Consortium, Sampson, Joshua, Black, Amanda, Jacobs, Kevin, Hoover, Robert N, Tucker, Margaret, and Chanock, Stephen J
Subjects: African Ancestry Prostate Cancer GWAS Consortium, Humans, Prostatic Neoplasms, Neoplasm Invasiveness, Genetic Predisposition to Disease, Case-Control Studies, Male, Genetic Loci, Neoplasm Grading
Abstract: Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49 × 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 × 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 × 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.
Published: 2015

25. Prostate Biopsies Can Be Omitted in Most Patients with a Positive Stockholm3 Test and Negative Prostate Magnetic Resonance Imaging

Author: Vinje, Cathrine Alvær, primary, Vigmostad, Maria Nyre, additional, Kjosavik, Svein R., additional, Grönberg, Henrik, additional, Gilje, Bjørnar, additional, and Skeie, Svein, additional
Published: 2023
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26. Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Author: Falagario, Ugo Giovanni, primary, Abbadi, Ahmad, additional, Remmers, Sebastiaan, additional, Björnebo, Lars, additional, Bogdanovic, Darko, additional, Martini, Alberto, additional, Valdman, Alexander, additional, Carrieri, Giuseppe, additional, Menon, Mani, additional, Akre, Olof, additional, Eklund, Martin, additional, Nordström, Tobias, additional, Grönberg, Henrik, additional, Lantz, Anna, additional, and Wiklund, Peter, additional
Published: 2023
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27. Prostate Cancer–specific and All-cause Mortality After Robot-assisted Radical Prostatectomy: 20 Years’ Report from the European Association of Urology Robotic Urology Section Scientific Working Group

Author: Falagario, Ugo Giovanni, primary, Knipper, Sophie, additional, Pellegrino, Francesco, additional, Martini, Alberto, additional, Akre, Olof, additional, Egevad, Lars, additional, Grönberg, Henrik, additional, Moschovas, Marcio Covas, additional, Bravi, Carlo Andrea, additional, Tran, Joshua, additional, Heiniger, Yasmin, additional, von Kempis, Antonius, additional, Schaffar, Robin, additional, Carrieri, Giuseppe, additional, Rochat, Charles-Henry, additional, Mottrie, Alexandre, additional, Ahlering, Thomas E., additional, John, Hubert, additional, Patel, Vipul, additional, Graefen, Markus, additional, and Wiklund, Peter, additional
Published: 2023
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28. The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort

Author: Möller, Axel, Olsson, Henrik, Grönberg, Henrik, Eklund, Martin, Aly, Markus, and Nordström, Tobias
Published: 2019
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29. Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies.

Author: Elliott, Katherine S, Zeggini, Eleftheria, McCarthy, Mark I, Gudmundsson, Julius, Sulem, Patrick, Stacey, Simon N, Thorlacius, Steinunn, Amundadottir, Laufey, Grönberg, Henrik, Xu, Jianfeng, Gaborieau, Valerie, Eeles, Rosalind A, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Muir, Kenneth, Hwang, Shih-Jen, Spitz, Margaret R, Zanke, Brent, Carvajal-Carmona, Luis, Brown, Kevin M, Australian Melanoma Family Study Investigators, Hayward, Nicholas K, Macgregor, Stuart, Tomlinson, Ian PM, Lemire, Mathieu, Amos, Christopher I, Murabito, Joanne M, Isaacs, William B, Easton, Douglas F, Brennan, Paul, PanScan Consortium, Barkardottir, Rosa B, Gudbjartsson, Daniel F, Rafnar, Thorunn, Hunter, David J, Chanock, Stephen J, Stefansson, Kari, and Ioannidis, John PA
Subjects: Australian Melanoma Family Study Investigators, PanScan Consortium, Humans, Neoplasms, Genetic Predisposition to Disease, Cooperative Behavior, Polymorphism, Single Nucleotide, Databases, Genetic, Hepatocyte Nuclear Factor 1-beta, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Databases, Genetic, General Science & Technology
Abstract: BackgroundGenome-wide association studies have found type 2 diabetes-associated variants in the HNF1B gene to exhibit reciprocal associations with prostate cancer risk. We aimed to identify whether these variants may have an effect on cancer risk in general versus a specific effect on prostate cancer only.Methodology/principal findingsIn a collaborative analysis, we collected data from GWAS of cancer phenotypes for the frequently reported variants of HNF1B, rs4430796 and rs7501939, which are in linkage disequilibrium (r(2) = 0.76, HapMap CEU). Overall, the analysis included 16 datasets on rs4430796 with 19,640 cancer cases and 21,929 controls; and 21 datasets on rs7501939 with 26,923 cases and 49,085 controls. Malignancies other than prostate cancer included colorectal, breast, lung and pancreatic cancers, and melanoma. Meta-analysis showed large between-dataset heterogeneity that was driven by different effects in prostate cancer and other cancers. The per-T2D-risk-allele odds ratios (95% confidence intervals) for rs4430796 were 0.79 (0.76, 0.83)] per G allele for prostate cancer (p
Published: 2010

30. Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Author: Darst, Burcu F., primary, Shen, Jiayi, additional, Madduri, Ravi K., additional, Rodriguez, Alexis A., additional, Xiao, Yukai, additional, Sheng, Xin, additional, Saunders, Edward J., additional, Dadaev, Tokhir, additional, Brook, Mark N., additional, Hoffmann, Thomas J., additional, Muir, Kenneth, additional, Wan, Peggy, additional, Le Marchand, Loic, additional, Wilkens, Lynne, additional, Wang, Ying, additional, Schleutker, Johanna, additional, MacInnis, Robert J., additional, Cybulski, Cezary, additional, Neal, David E., additional, Nordestgaard, Børge G., additional, Nielsen, Sune F., additional, Batra, Jyotsna, additional, Clements, Judith A., additional, Cancer BioResource, Australian Prostate, additional, Grönberg, Henrik, additional, Pashayan, Nora, additional, Travis, Ruth C., additional, Park, Jong Y., additional, Albanes, Demetrius, additional, Weinstein, Stephanie, additional, Mucci, Lorelei A., additional, Hunter, David J., additional, Penney, Kathryn L., additional, Tangen, Catherine M., additional, Hamilton, Robert J., additional, Parent, Marie-Élise, additional, Stanford, Janet L., additional, Koutros, Stella, additional, Wolk, Alicja, additional, Sørensen, Karina D., additional, Blot, William J., additional, Yeboah, Edward D., additional, Mensah, James E., additional, Lu, Yong-Jie, additional, Schaid, Daniel J., additional, Thibodeau, Stephen N., additional, West, Catharine M., additional, Maier, Christiane, additional, Kibel, Adam S., additional, Cancel-Tassin, Géraldine, additional, Menegaux, Florence, additional, John, Esther M., additional, Grindedal, Eli Marie, additional, Khaw, Kay-Tee, additional, Ingles, Sue A., additional, Vega, Ana, additional, Rosenstein, Barry S., additional, Teixeira, Manuel R., additional, Kogevinas, Manolis, additional, Cannon-Albright, Lisa, additional, Huff, Chad, additional, Multigner, Luc, additional, Kaneva, Radka, additional, Leach, Robin J., additional, Brenner, Hermann, additional, Hsing, Ann W., additional, Kittles, Rick A., additional, Murphy, Adam B., additional, Logothetis, Christopher J., additional, Neuhausen, Susan L., additional, Isaacs, William B., additional, Nemesure, Barbara, additional, Hennis, Anselm J., additional, Carpten, John, additional, Pandha, Hardev, additional, De Ruyck, Kim, additional, Xu, Jianfeng, additional, Razack, Azad, additional, Teo, Soo-Hwang, additional, Newcomb, Lisa F., additional, Fowke, Jay H., additional, Neslund-Dudas, Christine, additional, Rybicki, Benjamin A., additional, Gamulin, Marija, additional, Usmani, Nawaid, additional, Claessens, Frank, additional, Gago-Dominguez, Manuela, additional, Castelao, Jose Esteban, additional, Townsend, Paul A., additional, Crawford, Dana C., additional, Petrovics, Gyorgy, additional, Casey, Graham, additional, Roobol, Monique J., additional, Hu, Jennifer F., additional, Berndt, Sonja I., additional, Van Den Eeden, Stephen K., additional, Easton, Douglas F., additional, Chanock, Stephen J., additional, Cook, Michael B., additional, Wiklund, Fredrik, additional, Witte, John S., additional, Eeles, Rosalind A., additional, Kote-Jarai, Zsofia, additional, Watya, Stephen, additional, Gaziano, John M., additional, Justice, Amy C., additional, Conti, David V., additional, and Haiman, Christopher A., additional
Published: 2023
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31. AR and PI3K Genomic Profiling of Cell-free DNA Can Identify Poor Responders to Lutetium-177-PSMA Among Patients with Metastatic Castration-resistant Prostate Cancer

Author: Vanwelkenhuyzen, Jan, primary, Van Bos, Eva, additional, Van Bruwaene, Siska, additional, Lesage, Karl, additional, Maes, Alex, additional, Üstmert, Sezgin, additional, Lavent, Filip, additional, Beels, Laurence, additional, Grönberg, Henrik, additional, Ost, Piet, additional, Lindberg, Johan, additional, and De Laere, Bram, additional
Published: 2023
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32. Prostate Cancer IRE Study (PRIS): A Randomized Controlled Trial Comparing Focal Therapy to Radical Treatment in Localized Prostate Cancer

Author: Lantz, Anna, primary, Nordlund, Per, additional, Falagario, Ugo, additional, Jäderling, Fredrik, additional, Özbek, Orhan, additional, Clements, Mark, additional, Discacciati, Andrea, additional, Grönberg, Henrik, additional, Eklund, Martin, additional, Stricker, Phillip, additional, Emberton, Mark, additional, Aly, Markus, additional, and Nordström, Tobias, additional
Published: 2023
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33. External Validation of the Rotterdam Prostate Cancer Risk Calculator and Comparison with Stockholm3 for Prostate Cancer Diagnosis in a Swedish Population-based Screening Cohort

Author: Palsdottir, Thorgerdur, primary, Grönberg, Henrik, additional, Hilmisson, Arnaldur, additional, Eklund, Martin, additional, Nordström, Tobias, additional, and Vigneswaran, Hari T., additional
Published: 2023
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34. The ProBio trial: molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer

Author: Crippa, Alessio, De Laere, Bram, Discacciati, Andrea, Larsson, Berit, Connor, Jason T., Gabriel, Erin E., Thellenberg, Camilla, Jänes, Elin, Enblad, Gunilla, Ullen, Anders, Hjälm-Eriksson, Marie, Oldenburg, Jan, Ost, Piet, Lindberg, Johan, Eklund, Martin, and Grönberg, Henrik
Published: 2020
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35. Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia

Author: Österroos, Albin, Björklund, My, Eriksson, Anna, Lindberg, Johan, Nilsson, Christer, Mareschal, Sylvain, Rantalainen, Mattias, Grönberg, Henrik, and Lehmann, Sören
Published: 2020
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36. The economic burden of prostate cancer – a Swedish prevalence-based register study

Author: Hao, Shuang, Östensson, Ellinor, Eklund, Martin, Grönberg, Henrik, Nordström, Tobias, Heintz, Emelie, and Clements, Mark
Published: 2020
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37. Somatic Deletions in Hereditary Breast Cancers Implicate 13q21 as a Putative Novel Breast Cancer Susceptibility Locus

Author: Kainu, Tommi, Juo, Suh-Hang Hank, Desper, Richard, Schaffer, Alejandro A., Gillanders, Elizabeth, Rozenblum, Ester, Freas-Lutz, Diana, Weaver, Don, Stephan, Dietrich, Bailey-Wilson, Joan, Trikkonen, Mika, Syrjakoski, Kirsi, Kuukasjarvi, Tuula, Koivisto, Pasi, Karhu, Ritva, Holli, Kaija, Arason, Adalgeir, Johannesdottir, Gudrun, Bergthorsson, Jon Thor, Johannsdottir, Hrefna, Egilsson, Valgardur, Barkardottir, Rosa Bjork, Johannsson, Oskar, Haraldsson, Karin, Sandberg, Therese, Holmberg, Eva, Gronberg, Henrik, Olsson, Hakan, Borg, Ake, Vehmanen, Paula, Eerola, Hannaleena, Heikkila, Paivi, Pyrhonen, Seppo, and Nevanlinna, Heli
Published: 2000

38. Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Author: Darst, Burcu F, Shen, Jiayi, Madduri, Ravi K, Rodriguez, Alexis A, Xiao, Yukai, Sheng, Xin, Saunders, Edward J, Dadaev, Tokhir, Brook, Mark N, Hoffmann, Thomas J, Muir, Kenneth, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne, Wang, Ying, Schleutker, Johanna, MacInnis, Robert J, Cybulski, Cezary, Neal, David E, Nordestgaard, Børge G, Nielsen, Sune F, Batra, Jyotsna, Clements, Judith A, Cancer BioResource, Australian Prostate, Grönberg, Henrik, Pashayan, Nora, Travis, Ruth C, Park, Jong Y, Albanes, Demetrius, Weinstein, Stephanie, Mucci, Lorelei A, Hunter, David J, Penney, Kathryn L, Tangen, Catherine M, Hamilton, Robert J, Parent, Marie-Élise, Stanford, Janet L, Koutros, Stella, Wolk, Alicja, Sørensen, Karina D, Blot, William J, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Schaid, Daniel J, Thibodeau, Stephen N, West, Catharine M, Maier, Christiane, Kibel, Adam S, and Cancel-Tassin, Géraldine
Subjects: Male, Prostatic Neoplasms/genetics, Risk Factors, Humans, Black People/genetics, Genetic Predisposition to Disease, Multifactorial Inheritance/genetics, Genome-Wide Association Study
Abstract: Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
Published: 2023

39. AR and PI3K Genomic Profiling of Cell-free DNA Can Identify Poor Responders to Lutetium-177-PSMA Among Patients with Metastatic Castration-resistant Prostate Cancer

Author: Vanwelkenhuyzen, Jan, Van Bos, Eva, Van Bruwaene, Siska, Lesage, Karl, Maes, Alex, Üstmert, Sezgin, Lavent, Filip, Beels, Laurence, Grönberg, Henrik, Ost, Piet, Lindberg, Johan, and De Laere, Bram
Subjects: Cell-free DNA, Liquid biopsy, Biomarker, Circulating tumour DNA, Lutetium-177-PSMA, Metastatic castration-resistant prostate cancer
Abstract: UNLABELLED: Lutetium-177 prostate-specific membrane antigen radioligands (177Lu-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with 177Lu-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC (n = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of ≥50% during treatment. Among 46 patients who provided a blood sample for profiling before 177Lu-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p = 0.007) were independently associated with poor 177Lu-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted. PATIENT SUMMARY: We examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA. ispartof: Eur Urol Open Sci vol:53 pages:63-66 ispartof: location:Netherlands status: Published online
Published: 2023

40. Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry

Author: Darst, Burcu F., Shen, Jiayi, Madduri, Ravi K., Rodriguez, Alexis A., Xiao, Yukai, Sheng, Xin, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Hoffmann, Thomas J., Muir, Kenneth, Wan, Peggy, Marchand, Loic Le, Wilkens, Lynne, Wang, Ying, Schleutker, Johanna, MacInnis, Robert J., Cybulski, Cezary, Neal, David E., G. Nordestgaard, Børge, Nielsen, Sune F., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Travis, Ruth C., Park, Jong Y., Albanes, Demetrius, Weinstein, Stephanie, Mucci, Lorelei A., Hunter, David J., Penney, Kathryn L., Tangen, Catherine M., Hamilton, Robert J., Parent, Marie-Élise, Stanford, Janet L., Koutros, Stella, Wolk, Alicja, Sørensen, Karina D., Blot, William J., Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Schaid, Daniel J., Thibodeau, Stephen N., West, Catharine M., Maier, Christiane, Kibel, Adam S., Cancel-Tassin, Géraldine, Menegaux, Florence, John, Esther M., Grindedal, Eli Marie, Khaw, Kay-Tee, Ingles, Sue A., Vega, Ana, Rosenstein, Barry S., Teixeira, Manuel R., Kogevinas, Manolis, Cannon-Albright, Lisa, Huff, Chad, Multigner, Luc, Kaneva, Radka, Leach, Robin J., Brenner, Hermann, Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Neuhausen, Susan L., Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J., Carpten, John, Pandha, Hardev, De Ruyck, Kim, Xu, Jianfeng, Razack, Azad, Teo, Soo-Hwang, Newcomb, Lisa F., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Townsend, Paul A., Crawford, Dana C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Hu, Jennifer F., Berndt, Sonja I., Van Den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, Watya, Stephen, Gaziano, John M., Justice, Amy C., Conti, David V., and Haiman, Christopher A.
Subjects: Article
Abstract: Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS (269) ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS (269) . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS (269) had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS (269) constructed with fine-mapping.
Published: 2023

41. Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer

Author: Nordström, Tobias, Akre, Olof, Aly, Markus, Grönberg, Henrik, and Eklund, Martin
Published: 2018
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42. Data from Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer

Author: Klein, Robert J., primary, Halldén, Christer, primary, Cronin, Angel M., primary, Ploner, Alexander, primary, Wiklund, Fredrik, primary, Bjartell, Anders S., primary, Stattin, Pär, primary, Xu, Jianfeng, primary, Scardino, Peter T., primary, Offit, Kenneth, primary, Vickers, Andrew J., primary, Grönberg, Henrik, primary, and Lilja, Hans, primary
Published: 2023
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43. Supplementary Tables 1-6 from Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer

Author: Klein, Robert J., primary, Halldén, Christer, primary, Cronin, Angel M., primary, Ploner, Alexander, primary, Wiklund, Fredrik, primary, Bjartell, Anders S., primary, Stattin, Pär, primary, Xu, Jianfeng, primary, Scardino, Peter T., primary, Offit, Kenneth, primary, Vickers, Andrew J., primary, Grönberg, Henrik, primary, and Lilja, Hans, primary
Published: 2023
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44. PD38-11 THE STOCKHOLM3 PROSTATE CANCER SCREENING TRIAL (STHLM3): AN INTERIM ANALYSIS OF MORTALITY RESULTS AFTER 6.5 YEARS OF FOLLOW-UP

Author: Micoli, Chiara, primary, Crippa, Alessio, additional, Discacciati, Andrea, additional, Palsdottir, Thorgerdur, additional, Vigneswaran, Hari, additional, Aly, Markus, additional, Adolfsson, Jan, additional, Lindberg, Johan, additional, Wiklund, Peter, additional, Thompson, James, additional, Brandberg, Yvonne, additional, Clements, Mark, additional, Egevad, Lars, additional, Grönberg, Henrik, additional, Nordström, Tobias, additional, and Eklund, Martin, additional
Published: 2023
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45. PD15-04 PREDICTION OF PROSTATE CANCER SPECIFIC MORTALITY IN MEN UNDERGOING RADIOTHERAPY WITH OR WITHOUT HORMONAL TREATMENT, RISK STRATIFICATION BASED ON CLINICAL CHARACTERISTICS AND PSA TREATMENT RESPONSE

Author: Falagario, Ugo, primary, Bogdanovic, Darko, additional, Björnebo, Lars, additional, Abbadi, Ahmad, additional, Valdman, Alexander, additional, Eklund, Martin, additional, Nordström, Tobias, additional, Aly, Markus, additional, Grönberg, Henrik, additional, Wiklund, Peter, additional, and Lantz, Anna, additional
Published: 2023
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46. MP17-06 VALIDATION OF EAU RISK GROUPS FOR BIOCHEMICAL RECURRENCE AFTER RADIOTHERAPY AND RADICAL PROSTATECTOMY FOR PREDICTION OF PROSTATE CANCER MORTALITY

Author: Falagario, Ugo, primary, Bogdanovic, Darko, additional, Björnebo, Lars, additional, Abbadi, Ahmad, additional, Valdman, Alexander, additional, Eklund, Martin, additional, Nordström, Tobias, additional, Aly, Markus, additional, Grönberg, Henrik, additional, Lantz, Anna, additional, and Wiklund, Peter, additional
Published: 2023
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47. PD39-02 THE CAPIO S:T GORAN MODEL FOR PROSTATE CANCER DIAGNOSIS USING STOCKHOLM3, MAGNETIC RESONANCE IMAGING AND TARGETED BIOPSIES

Author: Palsdottir, Thorgerdur, primary, Grönberg, Henrik, additional, Vigneswaran, Hari, additional, and Söderbäck, Harald, additional
Published: 2023
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48. Supplementary Table 1 from Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Author: Fehringer, Gordon, primary, Kraft, Peter, primary, Pharoah, Paul D., primary, Eeles, Rosalind A., primary, Chatterjee, Nilanjan, primary, Schumacher, Fredrick R., primary, Schildkraut, Joellen M., primary, Lindström, Sara, primary, Brennan, Paul, primary, Bickeböller, Heike, primary, Houlston, Richard S., primary, Landi, Maria Teresa, primary, Caporaso, Neil, primary, Risch, Angela, primary, Amin Al Olama, Ali, primary, Berndt, Sonja I., primary, Giovannucci, Edward L., primary, Grönberg, Henrik, primary, Kote-Jarai, Zsofia, primary, Ma, Jing, primary, Muir, Kenneth, primary, Stampfer, Meir J., primary, Stevens, Victoria L., primary, Wiklund, Fredrik, primary, Willett, Walter C., primary, Goode, Ellen L., primary, Permuth, Jennifer B., primary, Risch, Harvey A., primary, Reid, Brett M., primary, Bezieau, Stephane, primary, Brenner, Hermann, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Hudson, Thomas J., primary, Kocarnik, Jonathan K., primary, Newcomb, Polly A., primary, Schoen, Robert E., primary, Slattery, Martha L., primary, White, Emily, primary, Adank, Muriel A., primary, Ahsan, Habibul, primary, Aittomäki, Kristiina, primary, Baglietto, Laura, primary, Blomquist, Carl, primary, Canzian, Federico, primary, Czene, Kamila, primary, dos-Santos-Silva, Isabel, primary, Eliassen, A. Heather, primary, Figueroa, Jonine D., primary, Flesch-Janys, Dieter, primary, Fletcher, Olivia, primary, Garcia-Closas, Montserrat, primary, Gaudet, Mia M., primary, Johnson, Nichola, primary, Hall, Per, primary, Hazra, Aditi, primary, Hein, Rebecca, primary, Hofman, Albert, primary, Hopper, John L., primary, Irwanto, Astrid, primary, Johansson, Mattias, primary, Kaaks, Rudolf, primary, Kibriya, Muhammad G., primary, Lichtner, Peter, primary, Liu, Jianjun, primary, Lund, Eiliv, primary, Makalic, Enes, primary, Meindl, Alfons, primary, Müller-Myhsok, Bertram, primary, Muranen, Taru A., primary, Nevanlinna, Heli, primary, Peeters, Petra H., primary, Peto, Julian, primary, Prentice, Ross L., primary, Rahman, Nazneen, primary, Sanchez, Maria Jose, primary, Schmidt, Daniel F., primary, Schmutzler, Rita K., primary, Southey, Melissa C., primary, Tamimi, Rulla, primary, Travis, Ruth C., primary, Turnbull, Clare, primary, Uitterlinden, Andre G., primary, Wang, Zhaoming, primary, Whittemore, Alice S., primary, Yang, Xiaohong R., primary, Zheng, Wei, primary, Buchanan, Daniel D., primary, Casey, Graham, primary, Conti, David V., primary, Edlund, Christopher K., primary, Gallinger, Steven, primary, Haile, Robert W., primary, Jenkins, Mark, primary, Le Marchand, Loïc, primary, Li, Li, primary, Lindor, Noralene M., primary, Schmit, Stephanie L., primary, Thibodeau, Stephen N., primary, Woods, Michael O., primary, Rafnar, Thorunn, primary, Gudmundsson, Julius, primary, Stacey, Simon N., primary, Stefansson, Kari, primary, Sulem, Patrick, primary, Chen, Y. Ann, primary, Tyrer, Jonathan P., primary, Christiani, David C., primary, Wei, Yongyue, primary, Shen, Hongbing, primary, Hu, Zhibin, primary, Shu, Xiao-Ou, primary, Shiraishi, Kouya, primary, Takahashi, Atsushi, primary, Bossé, Yohan, primary, Obeidat, Ma'en, primary, Nickle, David, primary, Timens, Wim, primary, Freedman, Matthew L., primary, Li, Qiyuan, primary, Seminara, Daniela, primary, Chanock, Stephen J., primary, Gong, Jian, primary, Peters, Ulrike, primary, Gruber, Stephen B., primary, Amos, Christopher I., primary, Sellers, Thomas A., primary, Easton, Douglas F., primary, Hunter, David J., primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, and Hung, Rayjean J., primary
Published: 2023
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49. Data from Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Author: Fehringer, Gordon, primary, Kraft, Peter, primary, Pharoah, Paul D., primary, Eeles, Rosalind A., primary, Chatterjee, Nilanjan, primary, Schumacher, Fredrick R., primary, Schildkraut, Joellen M., primary, Lindström, Sara, primary, Brennan, Paul, primary, Bickeböller, Heike, primary, Houlston, Richard S., primary, Landi, Maria Teresa, primary, Caporaso, Neil, primary, Risch, Angela, primary, Amin Al Olama, Ali, primary, Berndt, Sonja I., primary, Giovannucci, Edward L., primary, Grönberg, Henrik, primary, Kote-Jarai, Zsofia, primary, Ma, Jing, primary, Muir, Kenneth, primary, Stampfer, Meir J., primary, Stevens, Victoria L., primary, Wiklund, Fredrik, primary, Willett, Walter C., primary, Goode, Ellen L., primary, Permuth, Jennifer B., primary, Risch, Harvey A., primary, Reid, Brett M., primary, Bezieau, Stephane, primary, Brenner, Hermann, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Hudson, Thomas J., primary, Kocarnik, Jonathan K., primary, Newcomb, Polly A., primary, Schoen, Robert E., primary, Slattery, Martha L., primary, White, Emily, primary, Adank, Muriel A., primary, Ahsan, Habibul, primary, Aittomäki, Kristiina, primary, Baglietto, Laura, primary, Blomquist, Carl, primary, Canzian, Federico, primary, Czene, Kamila, primary, dos-Santos-Silva, Isabel, primary, Eliassen, A. Heather, primary, Figueroa, Jonine D., primary, Flesch-Janys, Dieter, primary, Fletcher, Olivia, primary, Garcia-Closas, Montserrat, primary, Gaudet, Mia M., primary, Johnson, Nichola, primary, Hall, Per, primary, Hazra, Aditi, primary, Hein, Rebecca, primary, Hofman, Albert, primary, Hopper, John L., primary, Irwanto, Astrid, primary, Johansson, Mattias, primary, Kaaks, Rudolf, primary, Kibriya, Muhammad G., primary, Lichtner, Peter, primary, Liu, Jianjun, primary, Lund, Eiliv, primary, Makalic, Enes, primary, Meindl, Alfons, primary, Müller-Myhsok, Bertram, primary, Muranen, Taru A., primary, Nevanlinna, Heli, primary, Peeters, Petra H., primary, Peto, Julian, primary, Prentice, Ross L., primary, Rahman, Nazneen, primary, Sanchez, Maria Jose, primary, Schmidt, Daniel F., primary, Schmutzler, Rita K., primary, Southey, Melissa C., primary, Tamimi, Rulla, primary, Travis, Ruth C., primary, Turnbull, Clare, primary, Uitterlinden, Andre G., primary, Wang, Zhaoming, primary, Whittemore, Alice S., primary, Yang, Xiaohong R., primary, Zheng, Wei, primary, Buchanan, Daniel D., primary, Casey, Graham, primary, Conti, David V., primary, Edlund, Christopher K., primary, Gallinger, Steven, primary, Haile, Robert W., primary, Jenkins, Mark, primary, Le Marchand, Loïc, primary, Li, Li, primary, Lindor, Noralene M., primary, Schmit, Stephanie L., primary, Thibodeau, Stephen N., primary, Woods, Michael O., primary, Rafnar, Thorunn, primary, Gudmundsson, Julius, primary, Stacey, Simon N., primary, Stefansson, Kari, primary, Sulem, Patrick, primary, Chen, Y. Ann, primary, Tyrer, Jonathan P., primary, Christiani, David C., primary, Wei, Yongyue, primary, Shen, Hongbing, primary, Hu, Zhibin, primary, Shu, Xiao-Ou, primary, Shiraishi, Kouya, primary, Takahashi, Atsushi, primary, Bossé, Yohan, primary, Obeidat, Ma'en, primary, Nickle, David, primary, Timens, Wim, primary, Freedman, Matthew L., primary, Li, Qiyuan, primary, Seminara, Daniela, primary, Chanock, Stephen J., primary, Gong, Jian, primary, Peters, Ulrike, primary, Gruber, Stephen B., primary, Amos, Christopher I., primary, Sellers, Thomas A., primary, Easton, Douglas F., primary, Hunter, David J., primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, and Hung, Rayjean J., primary
Published: 2023
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50. Supplementary Table 3 from Refining the Prostate Cancer Genetic Association within the JAZF1 Gene on Chromosome 7p15.2

Author: Prokunina-Olsson, Ludmila, primary, Fu, Yi-Ping, primary, Tang, Wei, primary, Jacobs, Kevin B., primary, Hayes, Richard B., primary, Kraft, Peter, primary, Berndt, Sonja I., primary, Wacholder, Sholom, primary, Yu, Kai, primary, Hutchinson, Amy, primary, Spencer Feigelson, Heather, primary, Thun, Michael J., primary, Diver, W. Ryan, primary, Albanes, Demetrius, primary, Virtamo, Jarmo, primary, Weinstein, Stephanie, primary, Schumacher, Fredrick R., primary, Cancel-Tassin, Geraldine, primary, Cussenot, Olivier, primary, Valeri, Antoine, primary, Andriole, Gerald L., primary, Crawford, E. David, primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, Kolonel, Laurence, primary, Le Marchand, Loic, primary, Siddiq, Afshan, primary, Riboli, Elio, primary, Travis, Ruth, primary, Kaaks, Rudolf, primary, Isaacs, William B., primary, Isaacs, Sarah D., primary, Grönberg, Henrik, primary, Wiklund, Fredrik, primary, Xu, Jianfeng, primary, Vatten, Lars J., primary, Hveem, Kristian, primary, Kumle, Merethe, primary, Tucker, Margaret, primary, Hoover, Robert N., primary, Fraumeni, Joseph F., primary, Hunter, David J., primary, Thomas, Gilles, primary, Chatterjee, Nilanjan, primary, Chanock, Stephen J., primary, and Yeager, Meredith, primary
Published: 2023
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