182 results on '"Martin, Richard M"'
Search Results
2. Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.
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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
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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.
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- 2021
3. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.
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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
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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
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- 2021
4. A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data
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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
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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.
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- 2020
5. Does testosterone mediate the relationship between vitamin D and prostate cancer progression? A systematic review and meta-analysis
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Robles, Luke A., Harrison, Sean, Tan, Vanessa Y., Beynon, Rhona, McAleenan, Alexandra, Higgins, Julian PT., Martin, Richard M., and Lewis, Sarah J.
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- 2022
- Full Text
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6. A collaborative analysis of individual participant data from 19 prospective studies assesses circulating vitamin D and prostate cancer risk
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Travis, Ruth C, Perez-Cornago, Aurora, Appleby, Paul N, Albanes, Demetrius, Joshu, Corinne E, Lutsey, Pamela L, Mondul, Alison M, Platz, Elizabeth A, Weinstein, Stephanie J, Layne, Tracy M, Helzlsouer, Kathy J, Visvanathan, Kala, Palli, Domenico, Peeters, Petra H, Bueno-de-Mesquita, Bas, Trichopoulou, Antonia, Gunter, Marc J, Tsilidis, Konstantinos K, Sánchez, Maria-Jose, Olsen, Anja, Brenner, Hermann, Schöttker, Ben, Perna, Laura, Holleczek, Bernd, Knekt, Paul, Rissanen, Harri, Yeap, Bu B, Flicker, Leon, Almeida, Osvaldo P, Wong, Yuen Yee Elizabeth, Chan, June M, Giovannucci, Edward L, Stampfer, Meir J, Ursin, Giske, Gislefoss, Randi E, Bjørge, Tone, Meyer, Haakon E, Blomhoff, Rune, Tsugane, Shoichiro, Sawada, Norie, English, Dallas R, Eyles, Darryl W, Heath, Alicia K, Williamson, Elizabeth J, Manjer, Jonas, Malm, Johan, Almquist, Martin, Marchand, Loic Le, Haiman, Christopher A, Wilkens, Lynne R, Schenk, Jeannette M, Tangen, Cathy M, Black, Amanda, Cook, Michael B, Huang, Wen-Yi, Ziegler, Regina G, Martin, Richard M, Hamdy, Freddie C, Donovan, Jenny L, Neal, David E, Touvier, Mathilde, Hercberg, Serge, Galan, Pilar, Deschasaux, Mélanie, Key, Timothy J, and Allen, Naomi E
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Clinical Trials and Supportive Activities ,Nutrition ,Cancer ,Prostate Cancer ,Urologic Diseases ,Prevention ,Aging ,Clinical Research ,Aged ,Case-Control Studies ,Cross-Sectional Studies ,Humans ,Male ,Middle Aged ,Odds Ratio ,Prospective Studies ,Prostatic Neoplasms ,Risk Assessment ,Risk Factors ,Vitamin D ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness (P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.
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- 2019
7. Prostate cancer–Exercise and Metformin Trial (Pre-EMpT): study protocol for a feasibility factorial randomized controlled trial in men with localised or locally advanced prostate cancer
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McGeagh, Lucy, Robles, Luke A., Persad, Raj, Rowe, Edward, Bahl, Amit, Aning, Jonathan, Koupparis, Anthony, Abrams, Paul, Perks, Claire, Holly, Jeffrey, Johnson, Lyndsey, Shiridzinomwa, Constance, Challapalli, Amarnath, Shingler, Ellie, Taylor, Hilary, Oxley, Jon, Sandu, Meda, Martin, Richard M., and Lane, J. Athene
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- 2022
- Full Text
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8. Optimising the use of the prostate- specific antigen blood test in asymptomatic men for early prostate cancer detection in primary care: report from a UK clinical consensus.
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Harding, Thomas A, Martin, Richard M, Merriel, Samuel WD, Jones, Robert, O'Sullivan, Joe M, Kirby, Mike, Olajide, Oluwabunmi, Norman, Alexander, Bhatt, Jaimin, Hulson, Oliver, Martins, Tanimola, Gnanapragasam, Vincent J, Aning, Jonathan, Burgess, Meg, Rosario, Derek J, Pashayan, Nora, Tesfai, Abel, Norori, Natalia, Rylance, Amy, and Seggie, Andrew
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EARLY detection of cancer ,PROSTATE cancer patients ,PRIMARY health care ,ASYMPTOMATIC patients ,PROSTATE-specific antigen - Abstract
Background: Screening is not recommended for prostate cancer in the UK. Asymptomatic men aged ≥50 years can request a prostate-specific antigen (PSA) test following counselling on potential harms and benefits. There are areas of clinical uncertainty among GPs, resulting in the content and quality of counselling varying. Aim: To produce a consensus that can influence guidelines for UK primary care on the optimal use of the PSA test in asymptomatic men for early prostate cancer detection. Design and setting: Prostate Cancer UK facilitated a RAND/UCLA consensus. Method: Statements covering five topics were developed with a subgroup of experts. A panel of 15 experts in prostate cancer scored (round one) statements on a scale of one (strongly disagree) to nine (strongly agree). Panellists met to discuss statements before rescoring (round two). A lived experience panel of seven men scored a subset of statements with outcomes fed into the main panel. Results: Of the initial 94 statements reviewed by the expert panel, a final 48/85 (56%) achieved consensus. In the absence of screening, there was consensus on proactive approaches to initiate discussions about the PSA test with men who were at higher-than-average risk. Conclusion: Improvements in the prostate cancer diagnostic pathway may have reduced some of the harms associated with PSA testing; however, several areas of uncertainty remain in relation to screening, including optimal PSA thresholds for referral and intervals for retesting. There is consensus on proactive approaches to testing in higher-than-average risk groups. This should prompt a review of current guidelines. [ABSTRACT FROM AUTHOR]
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- 2024
9. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
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Schumacher, Fredrick R, Al Olama, Ali Amin, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J, Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara, Goh, Chee, Brook, Mark N, Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Håkansson, Niclas, West, Catharine ML, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei A, Giovannucci, Edward, Andriole, Gerald L, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Beane Freeman, Laura E, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Stanford, Janet L, and Cybulski, Cezary
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Cancer ,Aging ,Prostate Cancer ,Genetics ,Urologic Diseases ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Case-Control Studies ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Prostatic Neoplasms ,Risk ,Profile Study ,Australian Prostate Cancer BioResource ,IMPACT Study ,Canary PASS Investigators ,Breast and Prostate Cancer Cohort Consortium ,PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium ,Cancer of the Prostate in Sweden ,Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci ,Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.
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- 2018
10. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
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Dadaev, Tokhir, Saunders, Edward J, Newcombe, Paul J, Anokian, Ezequiel, Leongamornlert, Daniel A, Brook, Mark N, Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R, Berndt, Sonja I, Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Tangen, Catherine M, Goodman, Phyllis, Thompson, Ian M, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine, Dunning, Alison M, Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Travis, Ruth C, Key, Tim J, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C, Rosenstein, Barry, Kerns, Sarah, Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, FitzGerald, Liesel M, Kibel, Adam S, Drake, Bettina F, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L, Stampfer, Meir, Park, Jong Y, and Sellers, Thomas A
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Genetics ,Aging ,Urologic Diseases ,Prostate Cancer ,Prevention ,Human Genome ,Cancer ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Algorithms ,Bayes Theorem ,Black People ,Chromosome Mapping ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Molecular Sequence Annotation ,Multivariate Analysis ,Polymorphism ,Single Nucleotide ,Prostatic Neoplasms ,Quantitative Trait Loci ,Risk ,White People ,PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium - Abstract
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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- 2018
11. A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk
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Travis, Ruth C, Appleby, Paul N, Martin, Richard M, Holly, Jeff MP, Albanes, Demetrius, Black, Amanda, Bueno-de-Mesquita, HB As, Chan, June M, Chen, Chu, Chirlaque, Maria-Dolores, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, Ferrucci, Luigi, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Hamdy, Freddie C, Helzlsouer, Kathy J, Hercberg, Serge, Hoover, Robert N, Janssen, Joseph AMJL, Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Metter, E Jeffrey, Mikami, Kazuya, Morris, Joan K, Neal, David E, Neuhouser, Marian L, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth A, Pollak, Michael, Price, Alison J, Roobol, Monique J, Schaefer, Catherine, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Touvier, Mathilde, Wald, Nicholas J, Weiss, Noel S, Ziegler, Regina G, Key, Timothy J, and Allen, Naomi E
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Aging ,Prostate Cancer ,Cancer ,Urologic Diseases ,Aged ,Humans ,Insulin-Like Growth Factor I ,Male ,Middle Aged ,Prostatic Neoplasms ,Risk Factors ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.
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- 2016
12. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies 1–3
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Key, Timothy J, Appleby, Paul N, Travis, Ruth C, Albanes, Demetrius, Alberg, Anthony J, Barricarte, Aurelio, Black, Amanda, Boeing, Heiner, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cook, Michael B, Donovan, Jenny L, Galan, Pilar, Gilbert, Rebecca, Giles, Graham G, Giovannucci, Edward, Goodman, Gary E, Goodman, Phyllis J, Gunter, Marc J, Hamdy, Freddie C, Heliövaara, Markku, Helzlsouer, Kathy J, Henderson, Brian E, Hercberg, Serge, Hoffman-Bolton, Judy, Hoover, Robert N, Johansson, Mattias, Khaw, Kay-Tee, King, Irena B, Knekt, Paul, Kolonel, Laurence N, Le Marchand, Loic, Männistö, Satu, Martin, Richard M, Meyer, Haakon E, Mondul, Alison M, Moy, Kristin A, Neal, David E, Neuhouser, Marian L, Palli, Domenico, Platz, Elizabeth A, Pouchieu, Camille, Rissanen, Harri, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Tjønneland, Anne, Touvier, Mathilde, Trichopoulou, Antonia, Weinstein, Stephanie J, Ziegler, Regina G, Zhou, Cindy Ke, Allen, Naomi E, Biomarkers, Endogenous Hormones Nutritional, and Group, Prostate Cancer Collaborative
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Urologic Diseases ,Nutrition ,Prostate Cancer ,Cancer ,Aging ,Clinical Research ,Adult ,Biomarkers ,Carotenoids ,Case-Control Studies ,Cohort Studies ,Cross-Sectional Studies ,Humans ,Lycopene ,Male ,Meta-Analysis as Topic ,Middle Aged ,Neoplasm Grading ,Neoplasm Staging ,Observational Studies as Topic ,Prospective Studies ,Prostate ,Prostatic Neoplasms ,Risk Factors ,Vitamin A ,alpha-Tocopherol ,prostate cancer ,carotenoids ,retinol ,tocopherols ,vitamin E ,vitamin A ,pooled analysis ,nested case-control study ,biomarkers ,Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group ,Engineering ,Medical and Health Sciences ,Nutrition & Dietetics ,Clinical sciences ,Nutrition and dietetics - Abstract
BackgroundIndividual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.ObjectiveThe objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.DesignPrincipal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.ResultsData were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.ConclusionsOverall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.
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- 2015
13. Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen
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Harrison, Sean, Tilling, Kate, Turner, Emma L., Martin, Richard M., Lennon, Rosie, Lane, J. Athene, Donovan, Jenny L., Hamdy, Freddie C., Neal, David E., Bosch, J. L. H. Ruud, and Jones, Hayley E.
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- 2020
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14. Leisure time television watching, computer use and risks of breast, colorectal and prostate cancer: A Mendelian randomisation analysis.
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Papadimitriou, Nikos, Kazmi, Nabila, Dimou, Niki, Tsilidis, Konstantinos K., Martin, Richard M., Lewis, Sarah J., Lynch, Brigid M., Hoffmeister, Michael, Sun-Seog Kweon, Li Li, Milne, Roger L., Sakoda, Lori C., Schoen, Robert E., Phipps, Amanda I., Figueiredo, Jane C., Peters, Ulrike, Dixon-Suen, Suzanne C., Gunter, Marc J., and Murphy, Neil
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COLORECTAL cancer ,PROSTATE cancer ,TELEVISION viewing ,LEISURE ,GENOME-wide association studies - Abstract
Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. Results: A 1-standard deviation (SD: 1.5h/day) increment in hours of television watching increased risk of breast cancer (OR per 1-SD: 1.15, 95% confidence interval [CI]: 1.05–1.26) and colorectal cancer (OR per 1-SD: 1.32, 95% CI: 1.16– 1.49) while there was little evidence of an association for prostate cancer risk (OR per 1-SD: 0.94, 95% CI: 0.84–1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1-SD: 1.08, 95% CI: 0.92–1.27; colorectal cancer, OR per 1-SD: 1.08, 95% CI: 0.90–1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk. Conclusions: Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Mendelian randomization does not support serum calcium in prostate cancer risk
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Yarmolinsky, James, Berryman, Katie, Langdon, Ryan, Bonilla, Carolina, PRACTICAL consortium, Davey Smith, George, Martin, Richard M., and Lewis, Sarah J.
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- 2018
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16. Prostate cancer survivors’ preferences on the delivery of diet and lifestyle advice: a pilot best-worst discrete choice experiment
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Robles, Luke A., Wright, Stuart J., Hackshaw-McGeagh, Lucy, Shingler, Ellie, Shiridzinomwa, Constance, Lane, J. Athene, Martin, Richard M., and Burden, Sorrel
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- 2020
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17. Developing new age-specific prostate-specific antigen thresholds for testing for prostate cancer
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Gilbert, Rebecca, Tilling, Kate, Martin, Richard M., Lane, J. Athene, Davis, Michael, Hamdy, Freddie C., Neal, David E., Donovan, Jenny L., and Metcalfe, Chris
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- 2018
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18. Does testosterone mediate the relationship between vitamin D and prostate cancer? A systematic review and meta-analysis protocol
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Robles, Luke A., Dawe, Karen, Martin, Richard M., Higgins, Julian P. T., and Lewis, Sarah J.
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- 2019
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19. Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis.
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Perez‐Cornago, Aurora, Smith‐Byrne, Karl, Hazelwood, Emma, Watling, Cody Z., Martin, Susan, Frayling, Timothy, Lewis, Sarah, Martin, Richard M., Yaghootkar, Hanieh, Travis, Ruth C., and Key, Timothy J.
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PROSTATE cancer ,DISEASE risk factors ,OBESITY ,BODY mass index ,AGE of onset - Abstract
Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two‐sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer. Methods: We examined the association of these genetically predicted adiposity‐related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). Results: In inverse‐variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61–1.19), 0.80 (0.53–1.23) and 0.97 (0.88–1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis
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Harrison, Sean, Lennon, Rosie, Holly, Jeff, Higgins, Julian P. T., Gardner, Mike, Perks, Claire, Gaunt, Tom, Tan, Vanessa, Borwick, Cath, Emmet, Pauline, Jeffreys, Mona, Northstone, Kate, Rinaldi, Sabina, Thomas, Stephen, Turner, Suzanne D., Pease, Anna, Vilenchick, Vicky, Martin, Richard M., and Lewis, Sarah J.
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- 2017
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21. The provision of dietary and physical activity advice for men diagnosed with prostate cancer: a qualitative study of the experiences and views of health care professionals, patients and partners
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Sutton, Eileen, Hackshaw-McGeagh, Lucy E., Aning, Jonathan, Bahl, Amit, Koupparis, Anthony, Persad, Raj, Martin, Richard M., and Lane, J. Athene
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- 2017
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22. Investigating the prostate specific antigen, body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful?
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Harrison, Sean, Tilling, Kate, Turner, Emma L., Lane, J. Athene, Simpkin, Andrew, Davis, Michael, Donovan, Jenny, Hamdy, Freddie C., Neal, David E., and Martin, Richard M.
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- 2016
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23. Impact of PSA testing on secondary care costs in England and Wales: estimates from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).
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Thorn, Joanna C., Turner, Emma L., Walsh, Eleanor I., Donovan, Jenny L., Neal, David E., Hamdy, Freddie C., Martin, Richard M., and Noble, Sian M.
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SECONDARY care (Medicine) ,MEDICAL care costs ,PROSTATE-specific antigen ,PROSTATE cancer ,PROSTATE cancer patients ,WATCHFUL waiting ,UROLOGISTS - Abstract
Background: Screening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers. Methods: The Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50–69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation. Results: In the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million. Conclusions: Introducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs. [ABSTRACT FROM AUTHOR]
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- 2023
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24. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer:a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
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Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, and consortium, The PRACTICAL
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Cancer och onkologi ,prospective analysis ,Epidemiology ,General Medicine ,prostate cancer ,aggressive prostate cancer ,Cancer and Oncology ,Mendelian randomization ,international consortia ,Insulin-like growth factor-I ,ICEP ,Bristol Population Health Science Institute - Abstract
Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
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- 2022
25. Validation of the Hospital Episode Statistics Outpatient Dataset in England
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Thorn, Joanna C., Turner, Emma, Hounsome, Luke, Walsh, Eleanor, Donovan, Jenny L., Verne, Julia, Neal, David E., Hamdy, Freddie C., Martin, Richard M., and Noble, Sian M.
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- 2016
- Full Text
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26. A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality
- Author
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Hackshaw-McGeagh, Lucy E., Perry, Rachel E., Leach, Verity A., Qandil, Sara, Jeffreys, Mona, Martin, Richard M., and Lane, J. Athene
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- 2015
- Full Text
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27. The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium
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Davies, Neil M., Gaunt, Tom R., Lewis, Sarah J., Holly, Jeff, Donovan, Jenny L., Hamdy, Freddie C., Kemp, John P., Eeles, Rosalind, Easton, Doug, Kote-Jarai, Zsofia, Al Olama, Ali Amin, Benlloch, Sara, Muir, Kenneth, Giles, Graham G., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher A., Schleutker, Johanna, Nordestgaard, Børge G., Travis, Ruth C., Neal, David, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L., Blot, William J., Thibodeau, Stephen, Maier, Christiane, Kibel, Adam S., Cybulski, Cezary, Cannon-Albright, Lisa, Brenner, Hermann, Park, Jong, Kaneva, Radka, Batra, Jyotsna, Teixeira, Manuel R., Pandha, Hardev, Lathrop, Mark, Smith, George Davey, Martin, Richard M., and PRACTICAL consortium
- Published
- 2015
- Full Text
- View/download PDF
28. Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study
- Author
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Burton, Anya, Martin, Richard M., Holly, Jeff, Lane, J. Athene, Donovan, Jenny L., Hamdy, Freddie C., Neal, David E., and Tilling, Kate
- Published
- 2013
29. Insulin-like growth factors (IGFs) and IGF-binding proteins in active monitoring of localized prostate cancer: a population-based observational study
- Author
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Rowlands, Mari-Anne, Tilling, Kate, Holly, Jeff M. P., Metcalfe, Chris, Gunnell, David, Lane, Athene, Davis, Michael, Donovan, Jenny, Hamdy, Freddie, Neal, David E., and Martin, Richard M.
- Published
- 2013
30. Associations of circulating retinol, vitamin E, and 1,25-dihydroxyvitamin D with prostate cancer diagnosis, stage, and grade
- Author
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Gilbert, Rebecca, Metcalfe, Chris, Fraser, William D., Donovan, Jenny, Hamdy, Freddie, Neal, David E., Lane, J. Athene, and Martin, Richard M.
- Published
- 2012
31. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis.
- Author
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Watts, Eleanor L, Perez-Cornago, Aurora, Fensom, Georgina K, Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D, Gunter, Marc J, Holmes, Michael V, Martin, Richard M, Tsilidis, Konstantinos K, Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, H Bas, Cohn, Barbara A, Deschasaux-Tanguy, Melanie, Dimou, Niki L, Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D, and Giles, Graham G
- Subjects
SOMATOMEDIN ,PROSTATE cancer ,RANDOMIZATION (Statistics) ,SOMATOMEDIN C ,INSULIN-like growth factor-binding proteins ,ANDROGEN receptors ,LONGITUDINAL method ,LINKAGE disequilibrium - Abstract
Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case–control study
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Gilbert, Rebecca, Bonilla, Carolina, Metcalfe, Chris, Lewis, Sarah, Evans, David M., Fraser, William D., Kemp, John P., Donovan, Jenny L., Hamdy, Freddie C., Neal, David E., Lane, J. Athene, Smith, George Davey, Lathrop, Mark, and Martin, Richard M.
- Published
- 2015
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33. A cross-sectional analysis of the association between diet and insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2, and IGFBP-3 in men in the United Kingdom
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Young, Nicholas J., Metcalfe, Chris, Gunnell, David, Rowlands, Mari-Anne, Lane, J. Athene, Gilbert, Rebecca, Avery, Kerry N. L., Davis, Michael, Neal, David E., Hamdy, Freddie C., Donovan, Jenny, Martin, Richard M., and Holly, Jeff M. P.
- Published
- 2012
34. Predictors of 25-hydroxyvitamin D and its association with risk factors for prostate cancer: evidence from the Prostate testing for cancer and Treatment study
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Gilbert, Rebecca, Martin, Richard M., Fraser, William D., Lewis, Sarah, Donovan, Jenny, Hamdy, Freddie, Neal, David E., Lane, J. Athene, and Metcalfe, Chris
- Published
- 2012
35. Serum insulin-like growth factors and mortality in localised and advanced clinically detected prostate cancer
- Author
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Rowlands, Mari-Anne, Holly, Jeff M. P., Hamdy, Freddie, Phillips, Joshua, Goodwin, Louise, Marsden, Gemma, Gunnell, David, Donovan, Jenny, Neal, David E., and Martin, Richard M.
- Published
- 2012
36. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis
- Author
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Gilbert, Rebecca, Martin, Richard M., Beynon, Rebecca, Harris, Ross, Savovic, Jelena, Zuccolo, Luisa, Bekkering, Geertruida E., Fraser, William D., Sterne, Jonathan A. C., and Metcalfe, Chris
- Published
- 2011
37. The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: evidence from the ProtecT (Prostate testing for cancer and Treatment) study
- Author
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Rowlands, Mari-Anne, Holly, Jeff M. P., Gunnell, David, Gilbert, Rebecca, Donovan, Jenny, Lane, J. Athene, Marsden, Gemma, Collin, Simon M., Hamdy, Freddie, Neal, David E., and Martin, Richard M.
- Published
- 2010
38. Blood pressure and risk of prostate cancer: cohort Norway (CONOR)
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Martin, Richard M., Vatten, Lars, Gunnell, David, and Romundstad, Pål
- Published
- 2010
39. The Association of Atopic Diseases with Breast, Prostate, and Colorectal Cancers: A Meta-Analysis
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Vojtechova, Petra and Martin, Richard M.
- Published
- 2009
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40. Components of the Metabolic Syndrome and Risk of Prostate Cancer: The HUNT 2 Cohort, Norway
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Martin, Richard M., Vatten, Lars, Gunnell, David, Romundstad, Pål, and Nilsen, Tom I. L.
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- 2009
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41. Childhood Stature and Adult Cancer Risk: The Boyd Orr Cohort
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Whitley, Elise, Martin, Richard M., Smith, George Davey, Holly, Jeff M. P., and Gunnell, David
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- 2009
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42. Cost-Effectiveness Analysis of Prostate Cancer Screening in the UK: A Decision Model Analysis Based on the CAP Trial.
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Keeney, Edna, Sanghera, Sabina, Martin, Richard M., Gulati, Roman, Wiklund, Fredrik, Walsh, Eleanor I., Donovan, Jenny L., Hamdy, Freddie, Neal, David E., Lane, J. Athene, Turner, Emma L., Thom, Howard, and Clements, Mark S.
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EARLY detection of cancer ,DECISION making ,PROSTATE cancer ,COST effectiveness ,MAGNETIC resonance imaging - Abstract
Background and Objective: Most guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK. Methods: We used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective. Results: All screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies. Conclusions: Of the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
43. Screening asymptomatic men for prostate cancer: A comparison of international guidelines on prostate-specific antigen testing.
- Author
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Jackson, Sherena D, de la Rue, May R, Greenslade, Thomas PL, John, Anna M, Wahid, Shahida, Martin, Richard M, Williams, Naomi J, and Turner, Emma L
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MEN'S health ,JUDGMENT (Psychology) ,LIFE expectancy ,SYSTEMATIC reviews ,EARLY detection of cancer ,MEDICAL protocols ,DECISION making ,INTERNATIONAL agencies ,PROSTATE-specific antigen ,MEDLINE ,PROSTATE tumors ,SYMPTOMS - Abstract
Objective: To summarise and compare the key recommendations on prostate-specific antigen (PSA)-based screening for prostate cancer, and so highlight where more evidence is required to facilitate consistent recommendations. Methods: The Medline database and websites of 18 national screening organisations and professional associations were searched between January 2010 and November 2020 to identify screening guidelines published in English, considering recent clinical trials. Results: Population-based PSA testing of asymptomatic men is not widely recommended. Guidelines emphasize shared patient-clinician decision making. For 'average-risk' men choosing to be screened, the recommended age varies from 50–55 to 70 years, alongside consideration of life expectancy (ranging from 7–15 years). Screening intervals, when specified, are biennial (most common), annual, or determined from baseline PSA. The earliest age for screening high-risk men (frequently defined as of African descent or with a family history of prostate cancer) is 40 years, but recommendations often defer to clinical judgement. Conclusions: Population screening of asymptomatic men is not widely recommended. Instead, balancing the potential harms and benefits of PSA testing is endorsed. Variation between guidelines stems from differing interpretations of key trials and could lead to clinician-dependent screening views. The development of clinical decision aids and international consensus on guidelines may help reduce national and international variation on how men are counselled. [ABSTRACT FROM AUTHOR]
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- 2022
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44. Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.
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Watts, Eleanor L., Perez‐Cornago, Aurora, Fensom, Georgina K., Smith‐Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno‐de‐Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., and Giles, Graham G.
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PROSTATE cancer ,CONSORTIA ,TESTOSTERONE ,BLOOD collection ,OLDER men ,LOGISTIC regression analysis - Abstract
Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone‐binding globulin (SHBG) with aggressive, overall and early‐onset prostate cancer. In blood‐based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse‐variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08‐1.40). In blood‐based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02‐1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08‐1.34; blood‐based: 1.03, 1.01‐1.05) and early‐onset prostate cancer (MR: 1.37, 1.09‐1.73; blood‐based: 1.08, 0.98‐1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood‐based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups. [ABSTRACT FROM AUTHOR]
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- 2022
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45. Cluster randomised triAl of PSA testing for Prostate cancer (CAP) Study: 15 year Statistical Analysis Plan:Version 1.0 13th January 2021
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Metcalfe, Chris, Sterne, Jonathan A C, and Martin, Richard M
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Statistical analysis plan ,Prostate cancer ,Randomized controlled trial ,PSA test ,Screening ,CAP Study - Abstract
This is the date-stamped pre-specified Statistical Analysis Plan (version 1.0) for the second analysis of the CAP outcomes, conducted once median 15 years clinical outcomes data have accumulated.
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- 2021
46. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
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Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, and Lu, Yong-Jie
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Male ,Urologic Diseases ,Aging ,Quantitative Trait Loci ,Medical and Health Sciences ,Risk Factors ,Clinical Research ,Odds Ratio ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Neoplasm Invasiveness ,Genetic Predisposition to Disease ,Aetiology ,Cancer ,Prevention ,Prostate Cancer ,Racial Groups ,Human Genome ,Prostatic Neoplasms ,Molecular Sequence Annotation ,Genomics ,Middle Aged ,Biological Sciences ,Phenotype ,Good Health and Well Being ,Genetic Loci ,Software ,Genome-Wide Association Study ,Statistical Distributions ,Developmental Biology - Abstract
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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- 2021
47. Functional and quality of life outcomes of localised prostate cancer treatments (Prostate Testing for Cancer and Treatment [ProtecT] study).
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Lane, Janet Athene, Donovan, Jenny L., Young, Grace J., Davis, Michael, Walsh, Eleanor I., Avery, Kerry N.L., Blazeby, Jane M., Mason, Malcolm D., Martin, Richard M., Peters, Tim J., Turner, Emma L., Wade, Julia, Bollina, Prasad, Catto, James W.F., Doherty, Alan, Gillatt, David, Gnanapragasam, Vincent, Hughes, Owen, Kockelbergh, Roger, and Kynaston, Howard
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PROSTATE cancer ,CANCER treatment ,PATIENT reported outcome measures ,RADICAL prostatectomy ,QUALITY of life ,FECAL incontinence - Abstract
Objective: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision‐making. Patients and Methods: Men aged 50–69 years diagnosed with localised prostate cancer by prostate‐specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external‐beam radiotherapy (EBRT) with concurrent androgen‐deprivation therapy (ADT) and 77 low‐dose‐rate brachytherapy (BT, not a randomised treatment). Patient‐reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results: Treatment‐received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion: Treatment decision‐making for localised prostate cancer can be informed by these 6‐year functional and QoL outcomes. [ABSTRACT FROM AUTHOR]
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- 2022
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48. Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received
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Neal, David E., Metcalfe, Chris, Donovan, Jenny L., Lane, J. Athene, Davis, Michael, Young, Grace J., Dutton, Susan J., Walsh, Eleanor I., Martin, Richard M., Peters, Tim. J., Turner, Emma L., Mason, Malcolm, Bryant, Richard, Bollina, Prasad, Catto, James, Doherty, Alan, Gillatt, David, Gnanapragasam, Vincent, Holding, Peter, Hughes, Owen, Kockelbergh, Roger, Kynaston, Howard, Oxley, Jon, Paul, Alan, Paez, Edgar, Rosario, Derek J., Rowe, Edward, Staffurth, John, Altman, Doug G., Hamdy, Freddie C., Peters, Tim J., Doble, Andrew, Powell, Philip, Prescott, Stephen, Rosario, Derek, Anderson, John B., Aning, Jonathan, Durkan, Garett, Koupparis, Anthony, Leung, Hing, Mariappan, Param, McNeill, Alan, Persad, Raj, Schwaibold, Hartwig, Tulloch, David, Wallace, Michael, Bonnington, Susan, Bradshaw, Lynne, Cooper, Deborah, Elliott, Emma, Herbert, Phillipa, Howson, Joanne, Jones, Amanda, Lennon, Teresa, Lyons, Norma, Moody, Hilary, Plumb, Claire, O'Sullivan, Tricia, Salter, Elizabeth, Thompson, Pauline, Tidball, Sarah, Blaikie, Jan, Gray, Catherine, Adam, Tonia, Askew, Sarah, Atkinson, Sharon, Baynes, Tim, Brain, Carole, Breen, Viv, Brunt, Sarah, Bryne, Sean, Bythem, Jo, Clarke, Jenny, Cloete, Jenny, Dark, Susan, Davis, Gill, Rue, Rachael De La, Denizot, Jane, Dewhurst, Elspeth, Dimes, Anna, Dixon, Nicola, Ebbs, Penny, Emmerson, Ingrid, Ferguson, Jill, Gadd, Ali, Geoghegan, Lisa, Grant, Alison, Grant, Collette, Godfrey, Rosemary, Goodwin, Louise, Hall, Susie, Hart, Liz, Harvey, Andrew, Hoult, Chloe, Hawkins, Sarah, Holling, Sharon, Innes, Alastair, Kilner, Sue, Marshall, Fiona, Mellen, Louise, Moore, Andrea, Napier, Sally, Needham, Julie, Pearse, Kevin, Pisa, Anna, Rees, Mark, Richards, Ellie, Robson, Lindsay, Roxburgh, Janet, Samuel, Nikki, Sharkey, Irene, Slater, Michael, Smith, Donna, Taggart, Pippa, Taylor, Helen, Taylor, Vicky, Thomas, Ayesha, Tomkies, Briony, Trewick, Nicola, Ward, Claire, Walker, Christy, Williams, Ayesha, Woodhouse, Colin, Wyber, Elizabeth, Bahl, Amit, Benson, Richard, Beresford, Mark, Ferguson, Catherine, Graham, John, Herbert, Chris, Howard, Grahame, James, Nick, Kirkbride, Peter, Law, Alastair, Loughrey, Carmel, McClaren, Duncan, Patterson, Helen, Pedley, Ian, Roberts, Trevor, Robinson, Angus, Russell, Simon, Symonds, Paul, Thanvi, Narottam, Vasanthan, Subramaniam, Wilson, Paula, Robinson, Mary, Bhattarai, Selina, Deshmukh, Neeta, Dormer, John, Fernando, Malee, Goepel, John, Griffiths, David, Grigor, Ken, Mayer, Nick, Varma, Murali, Warren, Anne, Appleby, Helen, Ash, Dominic, Aston, Dean, Bolton, Steven, Chalmers, Graham, Conway, John, Early, Nick, Geater, Tony, Goddall, Lynda, Heymann, Claire, Hicks, Deborah, Jones, Liza, Lamb, Susan, Lambert, Geoff, Lawrence, Gill, Lewis, Geraint, Lilley, John, MacLeod, Aileen, Massey, Pauline, McQueen, Alison, Moore, Rollo, Penketh, Lynda, Potterton, Janet, Roberts, Neil, Showler, Helen, Shuttleworth, Pam, Slade, Stephen, Steele, Alasdair, Swinscoe, James, Tiffany, Marie, Townley, John, Treeby, Jo, Weston, Michael, Wilkinson, Joyce, Williams, Lorraine, Wills, Lucy, Woodley, Owain, Yarrow, Sue, Brindle, Lucy, Davies, Linda, Dedman, Dan, Down, Elizabeth, Khazragui, Hanan, Noble, Sian, Taylor, Hilary, Tazewell, Marta, Wade, Julia, Walsh, Eleanor, Baker, Susan, Bellis-Sheldon, Elizabeth, Bougard, Chantal, Bowtell, Joanne, Brewer, Catherine, Burton, Chris, Charlton, Jennie, Christoforou, Nicholas, Clark, Rebecca, Coull, Susan, Croker, Christine, Currer, Rosemary, Daisey, Claire, Delaney, Gill, Donohue, Rose, Drew, Jane, Farmer, Rebecca, Fry, Susan, Haddow, Jean, Hale, Alex, Halpin, Susan, Harris, Belle, Hattrick, Barbara, Holmes, Sharon, Hunt, Helen, Jackson, Vicky, Johnson, Donna, Le Butt, Mandy, Leworthy, Jo, Liddiatt, Tanya, Martin, Alex, Mauree, Jainee, Moore, Susan, Moulam, Gill, Mutch, Jackie, Parker, Kathleen, Pawsey, Christopher, Purdie, Michelle, Robson, Teresa, Smith, Lynne, Stenton, Carole, Steuart-Feilding, Tom, Stott, Beth, Sully, Chris, Sutton, Caroline, Torrington, Carol, Wilkins, Zoe, Williams, Sharon, Wilson, Andrea, Weaver, Ashleigh, Albertsen, Peter, Adolfsson, Jan, Baum, Michael, McFarlane, Jon, Reid, Colette, Turner, Emma, Zietman, Anthony, Hill, Elizabeth, Ng, Siaw Yein, Williams, Naomi, Toole, Jessica, Davies, Charlotte, Hughes, Laura, Rowlands, Mari-Anne, Bell, Lindsey, Harrison, Sean, Mauree, Jainnee, Grant, Adrian, Roberts, Ian, Ashby, Deborah, Cowan, Richard, Fayers, Peter, Mellon, Killian, N’Dow, James, O’Brien, Tim, Sokhal, Michael, Dearnaley, David, Schröder, Fritz, Roberts, Tracy, and for the ProtecT Study Group, .
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Male ,medicine.medical_specialty ,Time Factors ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Urinary incontinence ,Active monitoring ,BTC (Bristol Trials Centre) ,Metastasis ,law.invention ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,ProtecT trial ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,External beam radiotherapy ,Watchful Waiting ,Aged ,Prostatectomy ,Disease progression ,Radiotherapy ,business.industry ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,Radical prostatectomy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Propensity score matching ,Cohort ,Disease Progression ,BRTC ,medicine.symptom ,Sexual function ,business ,Literatur Kommentiert - Abstract
Background: The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective: To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, Setting, and Participants: This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention: Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. Outcome Measurements and Statistical Analysis: Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and Limitations: According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa. Conclusions: Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient Summary: More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common.
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- 2020
49. Effect of green tea and lycopene on the insulin-like growth factor system:the ProDiet randomized controlled trial
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Biernacka, Kalina M., Holly, Jeff M.P., Martin, Richard M., Frankow, Aleksandra, Bull, Caroline J., Hamdy, Freddie C., Donovan, Jenny L., Neal, David E., Metcalfe, Chris, and Lane, Athene
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Male ,green tea ,Pilot Projects ,BTC (Bristol Trials Centre) ,Insulin-Like Growth Factor II ,Humans ,insulin-like growth factor-I ,Insulin-Like Growth Factor I ,Aged ,Tea ,insulin-like growth factor binding protein-3 ,Prostatic Neoplasms ,IGFBP-3 ,Middle Aged ,prostate cancer ,lycopene ,IGF-I ,Insulin-Like Growth Factor Binding Protein 3 ,Gene Expression Regulation ,Centre for Surgical Research ,Dietary Supplements ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,BRTC ,ICEP ,diet ,Research Paper ,Follow-Up Studies - Abstract
Supplemental Digital Content is available in the text., Whether prostate cancer (PCa) may be preventable by dietary interventions can be assessed in randomized trials using intermediate biomarkers of cancer risk or progression. We investigated whether lycopene or green tea modify circulating insulin-like growth factor (IGF) peptides in men at increased risk of PCa. Participants (aged 50–69 years) in one centre in the UK wide PCa testing and treatment trial (ProtecT) with prostate specific antigen between 2.0 and 2.95 ng/ml or negative biopsies, were randomized to daily lycopene (n = 44 assigned 15 mg capsules/day; 44 assigned a lycopene-rich diet; 45 assigned placebo) and green tea (n = 45 assigned 600 mg/day epigallocatechin gallate; 45 assigned green tea drink; 43 assigned placebo) for 6 months. The interventions significantly elevated the primary outcomes, serum epigallocatechin gallate and lycopene at 6 months of follow-up. We report here an exploratory analysis in which serum IGF-I, IGF-II, IGF binding protein (BP)-2 and IGFBP-3 were measured at baseline and 6 months of postintervention. A total of 133 men were randomized (34% of eligible men approached) and 130 had follow-up IGF peptides (98%). In intention-to-treat analyses, there was only weak evidence that lycopene or green tea influenced some aspects of serum IGF-I, IGF-II, IGFBP-2 or IGFBP-3. In men randomized to lycopene supplements, IGFBP-2 was nonsignificantly (50.9 ng/ml; 95% confidence interval: −51.2–152.9, P = 0.3) higher in comparison to placebo, whereas in men randomized to green tea supplements, IGFBP-3 was nonsignificantly (205.2 ng/ml; 95% confidence interval: −583.3–172.9, P = 0.3) lower than with placebo. In this small, pilot randomized controlled trial, there was little evidence that lycopene or green tea interventions influenced serum levels of IGF-I, IGF-II, IGFBBP-3 and IGFBP-2. However, the effects were imprecisely estimates and some observed trends may justify larger trials.
- Published
- 2019
50. Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.
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Hayes, Bryony L., Robinson, Timothy, Kar, Siddhartha, Ruth, Katherine S., Tsilidis, Konstantinos K., Frayling, Timothy, Murray, Anna, Martin, Richard M., Lawlor, Deborah A., and Richmond, Rebecca C.
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SEX hormones ,PROSTATE cancer ,BIOAVAILABILITY ,BREAST cancer ,GENOME-wide association studies ,BREAST ,DISEASE risk factors - Abstract
Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10
−8 ) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for: I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI:0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI: 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI:1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI:-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI: -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for: I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI: 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI: 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates. Author summary: Although previous studies have demonstrated that morning-preference chronotype is associated with reduced breast and prostate cancer risk, the role of sex hormones in this relationship has yet to be elucidated. In this study we use genetic variants strongly associated with morning-preference chronotype, total testosterone, bioavailable testosterone, sex-hormone binding globulin and oestradiol to explore the potential of these sex hormones to act as either mediators or confounders of this relationship. The findings of this study implicate testosterone as a potential mediator of the relationship between chronotype and both prostate and breast cancer risk, although results were inconsistent between methods. As such, further studies are warranted to better understand the mechanisms underlying this relationship in order to inform the development of sleep-based intervention studies that may help to reduce breast and prostate cancer risk in high-risk populations. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
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