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1. The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies

Author

Watts, Eleanor L, Perez‐Cornago, Aurora, Appleby, Paul N, Albanes, Demetrius, Ardanaz, Eva, Black, Amanda, Bueno‐de‐Mesquita, H Bas, Chan, June M, Chen, Chu, Chubb, SA Paul, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, English, Dallas R, Flicker, Leon, Freedman, Neal D, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Häggström, Christel, Haiman, Christopher, Hamdy, Freddie C, Hercberg, Serge, Holly, Jeff M, Huang, Jiaqi, Huang, Wen‐Yi, Johansson, Mattias, Kaaks, Rudolf, Kubo, Tatsuhiko, Lane, J Athene, Layne, Tracy M, Le Marchand, Loic, Martin, Richard M, Metter, E Jeffrey, Mikami, Kazuya, Milne, Roger L, Morris, Howard A, Mucci, Lorelei A, Neal, David E, Neuhouser, Marian L, Oliver, Steven E, Overvad, Kim, Ozasa, Kotaro, Pala, Valeria, Pernar, Claire H, Pollak, Michael, Rowlands, Mari‐Anne, Schaefer, Catherine A, Schenk, Jeannette M, Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Touvier, Mathilde, Trichopoulou, Antonia, Tsilidis, Konstantinos K, Van Den Eeden, Stephen K, Weinstein, Stephanie J, Wilkens, Lynne, Yeap, Bu B, Key, Timothy J, Allen, Naomi E, and Travis, Ruth C

Subjects
Cancer, Aging, Urologic Diseases, Adult, Aged, Aged, 80 and over, Anthropometry, Biomarkers, Tumor, Cross-Sectional Studies, Humans, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Male, Middle Aged, Neoplasms, Prospective Studies, Young Adult, IGFs, IGFBPs, pooled analysis, correlates, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Published
2019

2. Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma

Author

Porsbjerg, Celeste M., Menzies-Gow, Andrew N., Tran, Trung N., Murray, Ruth B., Unni, Bindhu, Audrey Ang, Shi Ling, Alacqua, Marianna, Al-Ahmad, Mona, Al-Lehebi, Riyad, Altraja, Alan, Belevskiy, Andrey S., Björnsdóttir, Unnur S., Bourdin, Arnaud, Busby, John, Canonica, G. Walter, Christoff, George C., Cosio, Borja G., Costello, Richard W., FitzGerald, J. Mark, Fonseca, João A., Hansen, Susanne, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Iwanaga, Takashi, Jackson, David J., Kocks, Janwillem W.H., Kallieri, Maria, Bruce Ko, Hsin-Kuo, Koh, Mariko Siyue, Larenas-Linnemann, Désirée, Lehtimäki, Lauri A., Loukides, Stelios, Lugogo, Njira, Maspero, Jorge, Papaioannou, Andriana I., Perez-de-Llano, Luis, Pitrez, Paulo Márcio, Popov, Todor A., Rasmussen, Linda M., Rhee, Chin Kook, Sadatsafavi, Mohsen, Schmid, Johannes, Siddiqui, Salman, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte, Upham, John W., Wang, Eileen, Wechsler, Michael E., Bulathsinhala, Lakmini, Carter, Victoria, Chaudhry, Isha, Eleangovan, Neva, Hosseini, Naeimeh, Rowlands, Mari-Anne, Price, David B., and van Boven, Job F.M.

Published
2022
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13. Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma

Author

Meghoufel, Z, Cherifi, F, Boukra, A, Terki, F, Porsbjerg, Celeste, Menzies-Gow, Andrew, Tran, Trung, Murray, Ruth, Unni, Bindhu, Audrey Ang, Shi Ling, Alacqua, Marianna, Al-Ahmad, Mona, Al-Lehebi, Riyad, Altraja, Alan, Belevskiy, Andrey, Björnsdóttir, Unnur, Bourdin, Arnaud, Busby, John, Canonica, G. Walter, Christoff, George, Cosio, Borja, Costello, Richard, FitzGerald, J. Mark, Fonseca, João, Hansen, Susanne, Heaney, Liam, Heffler, Enrico, Hew, Mark, Iwanaga, Takashi, Jackson, David, Kocks, Janwillem W.H., Kallieri, Maria, Bruce Ko, Hsin-Kuo, Koh, Mariko Siyue, Larenas-Linnemann, Désirée, Lehtimäki, Lauri, Loukides, Stelios, Lugogo, Njira, Maspero, Jorge, Papaioannou, Andriana, Perez-de-Llano, Luis, Pitrez, Paulo Márcio, Popov, Todor, Rasmussen, Linda, Rhee, Chin Kook, Sadatsafavi, Mohsen, Schmid, Johannes, Siddiqui, Salman, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos, Ulrik, Charlotte, Upham, John, Wang, Eileen, Wechsler, Michael, Bulathsinhala, Lakmini, Carter, Victoria, Chaudhry, Isha, Eleangovan, Neva, Hosseini, Naeimeh, Rowlands, Mari-Anne, Price, David, van Boven, Job FM., Groningen Research Institute for Asthma and COPD (GRIAC), Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Severe asthma, Biological Products, [SDV]Life Sciences [q-bio], Medizin, Biologics access, Omalizumab, 3. Good health, Biologics eligibility, Biological Therapy, 03 medical and health sciences, BIOLOGICS, 0302 clinical medicine, Prescriptions, 030228 respiratory system, Immunology and Allergy, Humans, ASTHMA, 030212 general & internal medicine, Anti-Asthmatic Agents, ComputingMilieux_MISCELLANEOUS, SEVERE ASTHMA
Abstract

BackgroundRegulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine.ObjectiveTo compare global differences in ease of access to biologics.MethodsIn April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access.ResultsBiologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti–IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower.ConclusionsAlthough some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world.

Published
2022

14. 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

Author

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, .

Subjects
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.

Published
2020

16. The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies

Author

Watts, Eleanor L., Perez-Cornago, Aurora, Appleby, Paul N., Albanes, Demetrius, Ardanaz, Eva, Black, Amanda, Bueno-de-Mesquita, H. Bas, Chan, June M., Chen, Chu, Chubb, S. A. Paul, Cook, Michael B., Deschasaux, Melanie, Donovan, Jenny L., English, Dallas R., Flicker, Leon, Freedman, Neal D., Galan, Pilar, Giles, Graham G., Giovannucci, Edward L., Gunter, Marc J., Habel, Laurel A., Häggström, Christel, Haiman, Christopher, Hamdy, Freddie C., Hercberg, Serge, Holly, Jeff M., Huang, Jiaqi, Huang, Wen-Yi, Johansson, Mattias, Kaaks, Rudolf, Kubo, Tatsuhiko, Lane, J. Athene, Layne, Tracy M., Le Marchand, Loic, Martin, Richard M., Metter, E. Jeffrey, Mikami, Kazuya, Milne, Roger L., Morris, Howard A., Mucci, Lorelei A., Neal, David E., Neuhouser, Marian L., Oliver, Steven E., Overvad, Kim, Ozasa, Kotaro, Pala, Valeria, Pernar, Claire H., Pollak, Michael, Rowlands, Mari-Anne, Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Touvier, Mathilde, Trichopoulou, Antonia, Tsilidis, Konstantinos K., Van Den Eeden, Stephen K., Weinstein, Stephanie J., Wilkens, Lynne, Yeap, Bu B., Key, Timothy J., Allen, Naomi E., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Appleby, Paul N., Albanes, Demetrius, Ardanaz, Eva, Black, Amanda, Bueno-de-Mesquita, H. Bas, Chan, June M., Chen, Chu, Chubb, S. A. Paul, Cook, Michael B., Deschasaux, Melanie, Donovan, Jenny L., English, Dallas R., Flicker, Leon, Freedman, Neal D., Galan, Pilar, Giles, Graham G., Giovannucci, Edward L., Gunter, Marc J., Habel, Laurel A., Häggström, Christel, Haiman, Christopher, Hamdy, Freddie C., Hercberg, Serge, Holly, Jeff M., Huang, Jiaqi, Huang, Wen-Yi, Johansson, Mattias, Kaaks, Rudolf, Kubo, Tatsuhiko, Lane, J. Athene, Layne, Tracy M., Le Marchand, Loic, Martin, Richard M., Metter, E. Jeffrey, Mikami, Kazuya, Milne, Roger L., Morris, Howard A., Mucci, Lorelei A., Neal, David E., Neuhouser, Marian L., Oliver, Steven E., Overvad, Kim, Ozasa, Kotaro, Pala, Valeria, Pernar, Claire H., Pollak, Michael, Rowlands, Mari-Anne, Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Touvier, Mathilde, Trichopoulou, Antonia, Tsilidis, Konstantinos K., Van Den Eeden, Stephen K., Weinstein, Stephanie J., Wilkens, Lynne, Yeap, Bu B., Key, Timothy J., Allen, Naomi E., and Travis, Ruth C.

Abstract

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Published
2019
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17. Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial

Author

Walsh, Eleanor I., Turner, Emma L., Lane, J. Athene, Donovan, Jenny L., Neal, David E., Hamdy, Freddie C., Martin, Richard M., Metcalfe, Chris, Sterne, Jonathan, Noble, Sian, Hill, Elizabeth, Ng, Siaw Yein, Williams, Naomi J, Down, Elizabeth A, Walsh, Eleanor, Thorn, Joanna, Davies, Charlotte, Hughes, Laura, Rowlands, Mari Anne, Bell, Lindsey, Ben-Shlomo, Yoav, Oliver, Steven E, Brindle, Peter, Evans, Simon, Baum, Michael, Albertsen, Peter, Roberts, Tracy, Robinson, Mary, Adolfsson, Jan, Dearnaley, David, Zeitman, Anthony, Schröder, Fritz, Peters, Tim, Holding, Peter, Lennon, Teresa, Bonnington, Sue, Mason, Malcolm, Oxley, Jon D, Holmberg, Lars, Pickard, Robert, Thompson, Simon, Menon, Usha, Reid, Colette, McFarlane, Jon, Bahl, Amit, Koupparis, Anthony, Tazewell, Marta, and Hatton-Brown, Genevieve

Subjects
Randomised controlled trial, Prostate cancer, Prostate specific antigen testing, Centre for Surgical Research, Screening, BRTC, BTC (Bristol Trials Centre), PSA testing
Abstract

BackgroundSocio-demographic characteristics are associated with participating in cancer screening and trials. We compared the characteristics of those responding with those not responding to a single invitation for PSA testing for prostate cancer as part of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).MethodsAge, rurality and deprivation among 197,763 men from 271 cluster-randomised primary care centres in the UK were compared between those responding (n=90,300) and not responding (n=100,953) to a prostate cancer testing invitation.Results There was little difference in age between responders and non-responders. Responders were slightly more likely to come from urban rather than rural areas and were slightly less deprived than those who did not respond. ConclusionThese data indicate similarities in age and only minor differences in deprivation and urban location between responders and non-responders. These differences were smaller, but in the same direction as observed in other screening trials.

Published
2016

18. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

Author

Bonilla, Carolina, Lewis, Sarah J, Rowlands, Mari-Anne, Gaunt, Tom R, Davey Smith, George, Gunnell, David, Palmer, Tom, Donovan, Jenny L, Hamdy, Freddie C, Neal, David E, Eeles, Rosalind, Easton, Doug, Kote-Jarai, Zsofia, Al Olama, Ali Amin, Benlloch, Sara, Muir, Kenneth, Giles, Graham G, Wiklund, Fredrik, Grönberg, Henrik, Haiman, Christopher A, Schleutker, Johanna, Nordestgaard, Børge G, Travis, Ruth C, 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, PRACTICAL consortium, Lathrop, Mark, Martin, Richard M, Holly, Jeff MP, Easton, Douglas [0000-0003-2444-3247], Khaw, Kay-Tee [0000-0002-8802-2903], and Apollo - University of Cambridge Repository

Subjects
Male, Prostatic Neoplasms, ALSPAC, Mendelian Randomization Analysis, Middle Aged, prostate cancer, insulin-like growth factor-binding proteins, Polymorphism, Single Nucleotide, PRACTICAL, United Kingdom, UKHLS, Insulin-Like Growth Factor Binding Proteins, single nucleotide polymorphisms, IGFBP3, Somatomedins, insulin-like growth factors, Case-Control Studies, Mendelian randomization, Humans, ProtecT, Longitudinal Studies, Neoplasm Grading, Aged, Genome-Wide Association Study, Neoplasm Staging
Abstract

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker.

Published
2016

19. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization:genetic variants as instruments for circulating levels

Author

Bonilla, Carolina, Lewis, Sarah, Rowlands, Mari-Anne, Gaunt, Tom, Davey Smith, George, Gunnell, David, Palmer, Tom, Donovan, Jenny, Hamdy, Freddie C, Neal, David E, 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, 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, The PRACTICAL, Consortium, Lathrop, Mark, Martin, Richard, and Holly, Jeffrey

Subjects
insulin-like growth factor-binding proteins, ALSPAC, prostate cancer, PRACTICAL, UKHLS, single nucleotide polymorphisms, Insulin-like growth factors, Centre for Surgical Research, IGFBP3, Mendelian randomization, ProtecT, ICEP
Abstract

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N∼900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs high (≥ 7) Gleason grade, localised vs advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/ml) on risk of high vs low grade disease as 1.14 (95% CI 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. This article is protected by copyright. All rights reserved.

Published
2016

21. Insulin-like growth factors (IGFs) and IGF-binding proteins in active monitoring of localized prostate cancer: a population-based observational study

Author

Rowlands, Mari-Anne, primary, Tilling, Kate, additional, Holly, Jeff M. P., additional, Metcalfe, Chris, additional, Gunnell, David, additional, Lane, Athene, additional, Davis, Michael, additional, Donovan, Jenny, additional, Hamdy, Freddie, additional, Neal, David E., additional, and Martin, Richard M., additional

Published
2012
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24. Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.

Author

Bonilla C, Lewis SJ, Rowlands MA, Gaunt TR, Davey Smith G, Gunnell D, Palmer T, Donovan JL, Hamdy FC, Neal DE, Eeles R, Easton D, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Wiklund F, Grönberg H, Haiman CA, Schleutker J, Nordestgaard BG, Travis RC, Pashayan N, Khaw KT, Stanford JL, Blot WJ, Thibodeau S, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Brenner H, Park J, Kaneva R, Batra J, Teixeira MR, Pandha H, Lathrop M, Martin RM, and Holly JM

Subjects
Aged, Case-Control Studies, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Mendelian Randomization Analysis methods, Middle Aged, Neoplasm Grading, Neoplasm Staging, Polymorphism, Single Nucleotide, Prostatic Neoplasms epidemiology, Prostatic Neoplasms pathology, United Kingdom epidemiology, Insulin-Like Growth Factor Binding Proteins genetics, Insulin-Like Growth Factor Binding Proteins metabolism, Prostatic Neoplasms blood, Prostatic Neoplasms genetics, Somatomedins genetics, Somatomedins metabolism
Abstract

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker., (© 2016 UICC.)

Published
2016
Full Text
View/download PDF

25. Metabolic imbalance and prostate cancer progression.

Author

Burton AJ, Tilling KM, Holly JM, Hamdy FC, Rowlands MA, Donovan JL, and Martin RM

Abstract

There is substantial evidence implicating environmental factors in the progression of prostate cancer. The metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly, or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocyte-derived peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells, providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations are made.

Published
2010

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