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1. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Author

Mikropoulos, C., Selkirk, C.G. (Christina), Saya, S. (Sibel), Bancroft, E.K. (Elizabeth), Vertosick, E. (Emily), Dadaev, T. (Tokhir), Brendler, C. (Charles), Page, E. (Elizabeth), Dias, A. (Alexander), Evans, D.G. (D Gareth), Rothwell, J. (Jeanette), Maehle, L., Axcrona, K., Richardson, K. (Kate), Eccles, D. (Diana), Jensen, T. (Thomas), Osther, P.J. (Palle J), Van Asperen, C.J. (Christi J), Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Hart, R. (Rachel), Glover, W. (Wayne), Lam, J. (Jimmy), Taylor, L. (Louise), Salinas, M., Feliubadaló, L. (L.), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra S), Conner, T. (Tom), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Ausems, M.G.E.M. (Margreet), Teixeira, M.R. (Manuel R), Maia, S. (Sofia), Izatt, L. (Louise), Schmutzler, R. (Rita), Rhiem, K. (Kerstin), Foulkes, W.D. (William), Boshari, T. (Talia), Davidson, R. (Rosemarie), Ruijs, M.W.G. (Marielle), Helderman-van den Enden, A.T.J.M. (Apollonia), Andrews, L. (Lesley), Walker, L.J. (Lisa), Snape, K. (Katie), Henderson, A. (Alex), Jobson, I. (Irene), Lindeman, G.J. (Geoffrey), Liljegren, A. (Annelie), Harris, M. (Marion), Adank, M.A. (Muriel), Kirk, J. (Judy), Taylor, A. (Amy), Susman, R. (Rachel), Chen-Shtoyerman, R. (Rakefet), Pachter, N. (Nicholas), Spigelman, A., Side, L. (Lucy), Zgajnar, J. (Janez), Mora, J. (Josefina), Brewer, C. (C.), Gadea, N. (Neus), Brady, A. (A.), Gallagher, D. (David), Os, T.A.M. (Theo) van, Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Barwell, J. (Julian), James, P.A. (Paul A), Murphy, D.G. (Declan), Friedman, E. (Eitan), Nicolai, N. (Nicola), Greenhalgh, T. (Trisha), Obeid, E. (Elias), Murthy, A.C. (Adeline C.), Copakova, L. (Lucia), McGrath, J. (John), Teo, S.-H. (Soo-Hwang), Strom, S. (Sara), Kast, K. (Karin), Leongamornlert, D.A. (Daniel A), Chamberlain, A. (Anthony), Pope, J. (Jenny), Newlin, A.C. (Anna C), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Castro, E. (Elena), Dearnaley, D. (David), Eyfjord, J. (Jorunn), Falconer, A., Foster, C.S. (Christopher S), Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Lubinski, J. (Jan), Grindedal, E.M. (Eli Marie), McKinley, E.T. (Enid), Shackleton, K. (Kylie), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Tricker, K. (Karen), Moss, S. (Sue), Kote-Jarai, Z., Vickers, A.J. (Andrew), Lilja, H. (Hans), Helfand, B.T. (Brian T), Eeles, R.A. (Rosalind A.), Mikropoulos, C., Selkirk, C.G. (Christina), Saya, S. (Sibel), Bancroft, E.K. (Elizabeth), Vertosick, E. (Emily), Dadaev, T. (Tokhir), Brendler, C. (Charles), Page, E. (Elizabeth), Dias, A. (Alexander), Evans, D.G. (D Gareth), Rothwell, J. (Jeanette), Maehle, L., Axcrona, K., Richardson, K. (Kate), Eccles, D. (Diana), Jensen, T. (Thomas), Osther, P.J. (Palle J), Van Asperen, C.J. (Christi J), Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Hart, R. (Rachel), Glover, W. (Wayne), Lam, J. (Jimmy), Taylor, L. (Louise), Salinas, M., Feliubadaló, L. (L.), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra S), Conner, T. (Tom), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Ausems, M.G.E.M. (Margreet), Teixeira, M.R. (Manuel R), Maia, S. (Sofia), Izatt, L. (Louise), Schmutzler, R. (Rita), Rhiem, K. (Kerstin), Foulkes, W.D. (William), Boshari, T. (Talia), Davidson, R. (Rosemarie), Ruijs, M.W.G. (Marielle), Helderman-van den Enden, A.T.J.M. (Apollonia), Andrews, L. (Lesley), Walker, L.J. (Lisa), Snape, K. (Katie), Henderson, A. (Alex), Jobson, I. (Irene), Lindeman, G.J. (Geoffrey), Liljegren, A. (Annelie), Harris, M. (Marion), Adank, M.A. (Muriel), Kirk, J. (Judy), Taylor, A. (Amy), Susman, R. (Rachel), Chen-Shtoyerman, R. (Rakefet), Pachter, N. (Nicholas), Spigelman, A., Side, L. (Lucy), Zgajnar, J. (Janez), Mora, J. (Josefina), Brewer, C. (C.), Gadea, N. (Neus), Brady, A. (A.), Gallagher, D. (David), Os, T.A.M. (Theo) van, Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Barwell, J. (Julian), James, P.A. (Paul A), Murphy, D.G. (Declan), Friedman, E. (Eitan), Nicolai, N. (Nicola), Greenhalgh, T. (Trisha), Obeid, E. (Elias), Murthy, A.C. (Adeline C.), Copakova, L. (Lucia), McGrath, J. (John), Teo, S.-H. (Soo-Hwang), Strom, S. (Sara), Kast, K. (Karin), Leongamornlert, D.A. (Daniel A), Chamberlain, A. (Anthony), Pope, J. (Jenny), Newlin, A.C. (Anna C), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Castro, E. (Elena), Dearnaley, D. (David), Eyfjord, J. (Jorunn), Falconer, A., Foster, C.S. (Christopher S), Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Lubinski, J. (Jan), Grindedal, E.M. (Eli Marie), McKinley, E.T. (Enid), Shackleton, K. (Kylie), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Tricker, K. (Karen), Moss, S. (Sue), Kote-Jarai, Z., Vickers, A.J. (Andrew), Lilja, H. (Hans), Helfand, B.T. (Brian T), and Eeles, R.A. (Rosalind A.)

Abstract

Background:Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.Methods:PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.Results:1634 participants had 3/43 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.Conclusions:PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Published
2018
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2. Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

Author

Rietschel, L. (Liz), Streit, F. (Fabian), Zhu, G. (Gu), McAloney, K. (Kerrie), Frank, J. (Josef), Couvy-Duchesne, B. (Baptiste), Witt, S.H. (Stephanie H), Binz, T.M. (Tina M.), McGrath, J. (John), Hickie, I.B. (Ian), Hansell, N.K. (Narelle), Wright, M.J. (Margaret J.), Gillespie, N.A. (Nathan A.), Forstner, A.J. (Andreas), Schulze, T.G. (Thomas), Wüst, S. (Stefan), Nöthen, M.M. (Markus), Baumgartner, M.R. (Markus R.), Walker, B.R. (Brian), Crawford, A.A. (Andrew A.), Colodro-Conde, L. (Lucía), Medland, S.E. (Sarah), Martin, N.G. (Nicholas G.), Rietschel, M. (Marcella), Rietschel, L. (Liz), Streit, F. (Fabian), Zhu, G. (Gu), McAloney, K. (Kerrie), Frank, J. (Josef), Couvy-Duchesne, B. (Baptiste), Witt, S.H. (Stephanie H), Binz, T.M. (Tina M.), McGrath, J. (John), Hickie, I.B. (Ian), Hansell, N.K. (Narelle), Wright, M.J. (Margaret J.), Gillespie, N.A. (Nathan A.), Forstner, A.J. (Andreas), Schulze, T.G. (Thomas), Wüst, S. (Stefan), Nöthen, M.M. (Markus), Baumgartner, M.R. (Markus R.), Walker, B.R. (Brian), Crawford, A.A. (Andrew A.), Colodro-Conde, L. (Lucía), Medland, S.E. (Sarah), Martin, N.G. (Nicholas G.), and Rietschel, M. (Marcella)

Abstract

Hair cortisol concentration (HCC) is a promising measure of long-Term hypothalamus-pituitary-Adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.

Published
2017
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3. Hair cortisol in twins:heritability and genetic overlap with psychological variables and stress-system genes

Author

Rietschel, L. (Liz), Streit, F. (Fabian), Zhu, G. (Gu), McAlone, K. (Kerrie), Frank, J. (Josef), Couvy-Duchesne, B. (Baptiste), Witt, S. H. (Stephanie H.), Binz, T. M. (Tina M.), McGrath, J. (John), Hickie, I. B. (Ian B.), Hansel, N. K. (Narelle K.), Wright, M. J. (Margaret J.), Gillespie, N. A. (Nathan A.), Forstner, A. J. (Andreas J.), Schulze, T. G. (Thomas G.), Wüst, S. (Stefan), Nöthen, M. M. (Markus M.), Baumgartner, M. R. (Markus R.), Walker, B. R. (Brian R.), Crawford, A. A. (Andrew A.), Colodro-Conde, L. (Lucía), Medland, S. E. (Sarah E.), Martin, N. G. (Nicholas G.), Rietschel, M. (Marcella), Rietschel, L. (Liz), Streit, F. (Fabian), Zhu, G. (Gu), McAlone, K. (Kerrie), Frank, J. (Josef), Couvy-Duchesne, B. (Baptiste), Witt, S. H. (Stephanie H.), Binz, T. M. (Tina M.), McGrath, J. (John), Hickie, I. B. (Ian B.), Hansel, N. K. (Narelle K.), Wright, M. J. (Margaret J.), Gillespie, N. A. (Nathan A.), Forstner, A. J. (Andreas J.), Schulze, T. G. (Thomas G.), Wüst, S. (Stefan), Nöthen, M. M. (Markus M.), Baumgartner, M. R. (Markus R.), Walker, B. R. (Brian R.), Crawford, A. A. (Andrew A.), Colodro-Conde, L. (Lucía), Medland, S. E. (Sarah E.), Martin, N. G. (Nicholas G.), and Rietschel, M. (Marcella)

Abstract

Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables., Consortia CORtisolNETwork (CORNET) Consortium Jennifer L. Bolton21 Caroline Hayward23 Nese Direk24,25 Anna Anderson21 Jennifer Huffman23 James F. Wilson26 Harry Campbell26 Igor Rudan26 Alan Wright23 Nicholas Hastie23 Sarah H. Wild26 Fleur P. Velders24 Albert Hofman24 Andre G. Uitterlinden24,27 Jari Lahti28 Katri Räikkönen28 Eero Kajantie29 Elisabeth Widen30 Aarno Palotie30,31 Johan G. Eriksson29,32,33,34,35 Marika Kaakinen36 Marjo-Riitta Järvelin36,37,38,39 Nicholas J. Timpson40 George Davey Smith40 Susan M. Ring41 David M. Evans40 Beate St Pourcain41 Toshiko Tanaka42 Yuri Milaneschi42,43 Stefania Bandinelli44 Luigi Ferrucci42 Pim van der Harst45,46,47 Judith GM Rosmalen48 Stephen JL Bakker49 Niek Verweij45 Robin PF Dullaart49 Anubha Mahajan50 Cecilia M. Lindgren50 Andrew Morris50 Lars Lind51 Erik Ingelsson51 Laura N. Anderson52 Craig E. Pennell53 Stephen J. Lye52 Stephen G. Matthews54 Joel Eriksson55 Dan Mellstrom55 Claes Ohlsson55 Jackie F. Price26 Mark WJ Strachan21 Rebecca M. Reynolds21 Henning Tiemeier24,56,57 Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (PGC) Stephan Ripke58,59,60 Manuel Mattheisen61,62,63 Abdel Abdellaoui64 Mark J. Adams65 Esben Agerbo66,8,67 Tracy M. Air68 Till FM Andlauer69,70 Silviu-Alin Bacanu71 Marie Bækvad-Hansen67,72 Aartjan TF Beekman43 David A. Bennett73 Klaus Berger74 Tim B. Bigdeli71,11 Jonas Bybjerg-Grauholm67,72 Enda M. Byrne5 Na Cai75 Enrique Castelao76 Toni-Kim Clarke65 Jonathan RI Coleman77 Converge Consortium78 Nick Craddock79 Udo Dannlowski80,81 Gareth Davies82 Gail Davies83 Eco. J. C. de Geus64,84 Philip De Jager85 Ian J. Deary83 Franziska Degenhardt12,13 Erin C. Dunn86,87,88 Erik A. Ehli82 Thalia C. Eley77 Valentina Escott-Price89 Tõnu Esko58,90,91,92 Hilary K. Finucane93,94 Michael Gill95 Scott D. Gordon96 Jakob Grove61,62,67,97 Lynsey S. Hall65,98 Thomas F. Hansen99,100 Christine Søholm Hansen67,72 Thomas F. Hansen101 Andrew C. Heath102 Anjali K. Henders5 Stefan Herms12,13,15 Per Hoffman

Published
2017

4. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: Results from the initial screening round of the IMPACT study

Author

Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Castro, E. (Elena), Lilja, H. (Hans), Vickers, A.J. (Andrew), Sjoberg, D. (Daniel), Assel, M. (Matthias), Foster, C.S. (Christopher), Mitchell, G. (Gillian), Drew, K. (Kate), Maehle, L., Axcrona, K., Evans, D.G. (Gareth), Bulman, B., Eccles, D. (Diana), McBride, D. (Donna), Asperen, C.J. (Christi) van, Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), Bojesen, S.E. (Stig), Skytte, A.-B. (Anne-Bine), Lam, J. (Jimmy), Taylor, L. (Lorne), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Blanco, I. (Ignacio), Salinas, M., Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra), Conner, T. (Tom), Ausems, M.G.E.M. (Margreet), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Teixeira, P.J., Maia, S. (Sofia), Foulkes, W.D. (William), Taherian, N. (Nassim), Ruijs, M.W.G. (Marielle), Enden, A.T.H.-V. (Apollonia T. Helderman-Van) den, Izatt, L. (Louise), Davidson, R. (Rosemarie), Adank, M.A. (Muriel), Walker, L.J. (Lisa), Schmutzler, R.K. (Rita), Tucker, K. (Kathryn), Kirk, J. (Judy), Hodgson, S.V. (Shirley), Harris, M. (Marion), Douglas, F. (Fiona), Lindeman, G.J. (Geoffrey), Zgajnar, J. (Janez), Tischkowitz, M. (Marc), Clowes, V., Susman, R. (Rachel), Ramon Y Cajal, T., Patcher, N. (Nicholas), Gadea, N. (Neus), Spigelman, A., Os, T.A.M. (Theo) van, Liljegren, A. (Annelie), Side, L. (Lucy), Brewer, C. (Carole), Brady, A.F. (Angela), Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Friedman, E. (Eitan), Chen-Shtoyerman, R. (Rakefet), Amor, D. (David), Copakova, L. (Lucia), Barwell, J. (Julian), Giri, V.N. (Veda), Murthy, A.C. (Adeline C.), Nicolai, N. (Nicola), Teo, S.-H. (Soo-Hwang), Greenhalgh, T. (Trisha), Strom, S., Henderson, A. (Alex), McGrath, J. (John), Gallagher, D. (David), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Dearnaley, D. (David), Costello, A. (Anthony), Eyfjord, J., Rothwell, J. (Jeanette), Falconer, A., Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Kote-Jarai, Z., Lubinski, J. (Jan), Melia, J., McKinley, E.T. (Enid), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Wilson, P., Killick, S.R., Moss, S.M. (Sue), Eeles, R. (Rosalind), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Castro, E. (Elena), Lilja, H. (Hans), Vickers, A.J. (Andrew), Sjoberg, D. (Daniel), Assel, M. (Matthias), Foster, C.S. (Christopher), Mitchell, G. (Gillian), Drew, K. (Kate), Maehle, L., Axcrona, K., Evans, D.G. (Gareth), Bulman, B., Eccles, D. (Diana), McBride, D. (Donna), Asperen, C.J. (Christi) van, Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), Bojesen, S.E. (Stig), Skytte, A.-B. (Anne-Bine), Lam, J. (Jimmy), Taylor, L. (Lorne), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Blanco, I. (Ignacio), Salinas, M., Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra), Conner, T. (Tom), Ausems, M.G.E.M. (Margreet), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Teixeira, P.J., Maia, S. (Sofia), Foulkes, W.D. (William), Taherian, N. (Nassim), Ruijs, M.W.G. (Marielle), Enden, A.T.H.-V. (Apollonia T. Helderman-Van) den, Izatt, L. (Louise), Davidson, R. (Rosemarie), Adank, M.A. (Muriel), Walker, L.J. (Lisa), Schmutzler, R.K. (Rita), Tucker, K. (Kathryn), Kirk, J. (Judy), Hodgson, S.V. (Shirley), Harris, M. (Marion), Douglas, F. (Fiona), Lindeman, G.J. (Geoffrey), Zgajnar, J. (Janez), Tischkowitz, M. (Marc), Clowes, V., Susman, R. (Rachel), Ramon Y Cajal, T., Patcher, N. (Nicholas), Gadea, N. (Neus), Spigelman, A., Os, T.A.M. (Theo) van, Liljegren, A. (Annelie), Side, L. (Lucy), Brewer, C. (Carole), Brady, A.F. (Angela), Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Friedman, E. (Eitan), Chen-Shtoyerman, R. (Rakefet), Amor, D. (David), Copakova, L. (Lucia), Barwell, J. (Julian), Giri, V.N. (Veda), Murthy, A.C. (Adeline C.), Nicolai, N. (Nicola), Teo, S.-H. (Soo-Hwang), Greenhalgh, T. (Trisha), Strom, S., Henderson, A. (Alex), McGrath, J. (John), Gallagher, D. (David), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Dearnaley, D. (David), Costello, A. (Anthony), Eyfjord, J., Rothwell, J. (Jeanette), Falconer, A., Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Kote-Jarai, Z., Lubinski, J. (Jan), Melia, J., McKinley, E.T. (Enid), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Wilson, P., Killick, S.R., Moss, S.M. (Sue), and Eeles, R. (Rosalind)

Abstract

Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high

Published
2014
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