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4. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Author

Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon Y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Offman J., Kote-Jarai Z., and Eeles R.A.

Abstract

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHOD(S): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This

Published
2022

5. The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening

Author

Benafif, S, Ni Raghallaigh, H, McGrowder, E, Saunders, EJ, Brook, MN, Saya, S, Rageevakumar, R, Wakerell, S, James, D, Chamberlain, A, Taylor, N, Hogben, M, Benton, B, D'Mello, L, Myhill, K, Mikropoulos, C, Bowen-Perkins, H, Rafi, I, Ferris, M, Beattie, A, Kuganolipava, S, Sevenoaks, T, Bower, J, Kumar, P, Hazell, S, deSouza, NM, Antoniou, A, Bancroft, E, Kote-Jarai, Z, Eeles, R, Benafif, S, Ni Raghallaigh, H, McGrowder, E, Saunders, EJ, Brook, MN, Saya, S, Rageevakumar, R, Wakerell, S, James, D, Chamberlain, A, Taylor, N, Hogben, M, Benton, B, D'Mello, L, Myhill, K, Mikropoulos, C, Bowen-Perkins, H, Rafi, I, Ferris, M, Beattie, A, Kuganolipava, S, Sevenoaks, T, Bower, J, Kumar, P, Hazell, S, deSouza, NM, Antoniou, A, Bancroft, E, Kote-Jarai, Z, and Eeles, R

Abstract

OBJECTIVES: To assess the feasibility and uptake of a community-based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men. SUBJECTS AND METHODS: Healthy males aged 55-69 years were invited to participate via their general practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using a study specific assay. Genetic risk was based on genotyping 130 germline PCa risk single nucleotide polymorphisms (SNPs). A polygenic risk score (PRS) was calculated for each participant using the sum of weighted alleles for 130 SNPs. Study participants with a PRS lying above the 90th centile value were invited for PCa screening by prostate magnetic resonance imaging (MRI) and biopsy. RESULTS: Invitation letters were sent to 1434 men. The overall study uptake was 26% (375/1436) and 87% of responders were eligible for study entry. DNA genotyping data were available for 297 men and 25 were invited for screening. After exclusions due to medical comorbidity/invitations declined, 18 of 25 men (72%) underwent MRI and biopsy of the prostate. There were seven diagnoses of PCa (38.9%). All cancers were low-risk and were managed with active surveillance. CONCLUSION: The BARCODE1 Pilot has shown this community study in the UK to be feasible, with an overall uptake of 26%. The main BARCODE1 study is now open and will recruit 5000 men. The results of BARCODE1 will be important in defining the role of genetic profiling in targeted PCa population screening. Patient Summary What is the paper about? Very few prostate cancer screening programmes currently exist anywhere in the world. Our pilot study investigated if men in the UK would find it acceptable to have a genetic test based on a saliva sample to examin

Published
2022

10. 124 Could change in neoadjuvant chemotherapy regimen after 3 cycles lead to better outcomes in inoperable ovarian cancer?

Author

Adeleke, S, primary, Brown, N, additional, Choy, A, additional, Ahmed, Z, additional, Tsirekidze, A, additional, Ramachandran, V, additional, Ramanaidu, S, additional, Haslam, A, additional, Galante, J, additional, Shi, J, additional, George, S, additional, Davis, A, additional, Mikropoulos, C, additional, Waters, J, additional, Summers, J, additional, and Jyothirmayi, R, additional

Published
2021
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12. 414P Does adjuvant chemotherapy compared to surveillance improve recurrence free and overall survival in stage 3 rectal cancer patients?

Author

Adeleke, S.M., primary, George, S., additional, Galante, J.R., additional, Karova, M., additional, Dahal, L., additional, Choy, A., additional, Elwes, F., additional, Brown, N.F., additional, Summers, J., additional, Edwards, A.A., additional, Durve, M., additional, Mikropoulos, C., additional, Lees, K., additional, Hall, J., additional, Shah, R., additional, Hill, M., additional, Raman, R., additional, and Clarke, A., additional

Published
2021
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13. Prevalence of the HOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes

Author

Kote-Jarai, Z., Mikropoulos, C., Leongamornlert, D. A., Dadaev, T., Tymrakiewicz, M., Saunders, E. J., Jones, M., Jugurnauth-Little, S., Govindasami, K., Guy, M., Hamdy, F. C., Donovan, J. L., Neal, D. E., Lane, J. A., Dearnaley, D., Wilkinson, R. A., Sawyer, E. J., Morgan, A., Antoniou, A. C., Eeles, R. A., Hall, Per, Berchuck, Andrew, Dennis, Joe, Dunning, Alison M., Lee, Andrew, Dicks, Ed, Simard, Jacques, Tessier, Daniel C., Bacot, Francois, Vincent, Daniel, LaBoissière, Sylvie, Robidoux, Frederic, Bojesen, Stig E., Nielsen, Sune F., and Nordestgaard, Borge G.

Published
2015
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15. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Bancroft, EK, Page, EC, Brook, MN, Thomas, S, Taylor, N, Pope, J, McHugh, J, Jones, A-B, Karlsson, Q, Merson, S, Ong, KR, Hoffman, J, Huber, C, Maehle, L, Grindedal, EM, Stormorken, A, Evans, DG, Rothwell, J, Lalloo, F, Brady, AF, Bartlett, M, Snape, K, Hanson, H, James, P, McKinley, J, Mascarenhas, L, Syngal, S, Ukaegbu, C, Side, L, Thomas, T, Barwell, J, Teixeira, MR, Izatt, L, Suri, M, Macrae, FA, Poplawski, N, Chen-Shtoyerman, R, Ahmed, M, Musgrave, H, Nicolai, N, Greenhalgh, L, Brewer, C, Pachter, N, Spigelman, AD, Azzabi, A, Helfand, BT, Halliday, D, Buys, S, Cajal, TRY, Donaldson, A, Cooney, KA, Harris, M, McGrath, J, Davidson, R, Taylor, A, Cooke, P, Myhill, K, Hogben, M, Aaronson, NK, Ardern-Jones, A, Bangma, CH, Castro, E, Dearnaley, D, Dias, A, Dudderidge, T, Eccles, DM, Green, K, Eyfjord, J, Falconer, A, Foster, CS, Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lilja, H, Lindeman, GJ, Lubinski, J, Axcrona, K, Mikropoulos, C, Mitra, A, Moynihan, C, Raghallaigh, HN, Rennert, G, Collier, R, Offman, J, Kote-Jarai, Z, Eeles, RA, Bancroft, EK, Page, EC, Brook, MN, Thomas, S, Taylor, N, Pope, J, McHugh, J, Jones, A-B, Karlsson, Q, Merson, S, Ong, KR, Hoffman, J, Huber, C, Maehle, L, Grindedal, EM, Stormorken, A, Evans, DG, Rothwell, J, Lalloo, F, Brady, AF, Bartlett, M, Snape, K, Hanson, H, James, P, McKinley, J, Mascarenhas, L, Syngal, S, Ukaegbu, C, Side, L, Thomas, T, Barwell, J, Teixeira, MR, Izatt, L, Suri, M, Macrae, FA, Poplawski, N, Chen-Shtoyerman, R, Ahmed, M, Musgrave, H, Nicolai, N, Greenhalgh, L, Brewer, C, Pachter, N, Spigelman, AD, Azzabi, A, Helfand, BT, Halliday, D, Buys, S, Cajal, TRY, Donaldson, A, Cooney, KA, Harris, M, McGrath, J, Davidson, R, Taylor, A, Cooke, P, Myhill, K, Hogben, M, Aaronson, NK, Ardern-Jones, A, Bangma, CH, Castro, E, Dearnaley, D, Dias, A, Dudderidge, T, Eccles, DM, Green, K, Eyfjord, J, Falconer, A, Foster, CS, Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lilja, H, Lindeman, GJ, Lubinski, J, Axcrona, K, Mikropoulos, C, Mitra, A, Moynihan, C, Raghallaigh, HN, Rennert, G, Collier, R, Offman, J, Kote-Jarai, Z, and Eeles, RA

Abstract

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This s

Published
2021

17. Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY)

Author

Bancroft, EK, Saya, S, Brown, E, Thomas, S, Taylor, N, Rothwell, J, Pope, J, Chamberlain, A, Page, E, Benafif, S, Hanson, H, Dias, A, Mikropoulos, C, Izatt, L, Side, L, Walker, L, Donaldson, A, Cook, JA, Barwell, J, Wiles, V, Limb, L, Eccles, DM, Leach, MO, Shanley, S, Gilbert, FJ, Gallagher, D, Rajashanker, B, Whitehouse, RW, Koh, D-M, Sohaib, SA, Evans, DG, Eeles, RA, Walker, LG, Bancroft, EK, Saya, S, Brown, E, Thomas, S, Taylor, N, Rothwell, J, Pope, J, Chamberlain, A, Page, E, Benafif, S, Hanson, H, Dias, A, Mikropoulos, C, Izatt, L, Side, L, Walker, L, Donaldson, A, Cook, JA, Barwell, J, Wiles, V, Limb, L, Eccles, DM, Leach, MO, Shanley, S, Gilbert, FJ, Gallagher, D, Rajashanker, B, Whitehouse, RW, Koh, D-M, Sohaib, SA, Evans, DG, Eeles, RA, and Walker, LG

Abstract

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

Published
2020

19. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

Author

Teixeira M.R., Rhiem K., Izatt L., Tripathi V., Cardoso M., Foulkes W.D., Aprikian A., van Randeraad H., Davidson R., Longmuir M., Ruijs M.W.G., Adank M., Williams R., Andrews L., Murphy D.G., Halliday D., Walker L., Liljegren A., Carlsson S., Azzabi A., Jobson I., Morton C., Shackleton K., Snape K., Hanson H., Harris M., Tischkowitz M., Taylor A., Kirk J., Susman R., Chen-Shtoyerman R., Spigelman A., Pachter N., Ahmed M., Ramon y Cajal T., Zgajnar J., Brewer C., Gadea N., Brady A.F., van Os T., Gallagher D., Johannsson O., Donaldson A., Barwell J., Nicolai N., Friedman E., Obeid E., Greenhalgh L., Murthy V., Copakova L., Saya S., McGrath J., Cooke P., Ronlund K., Richardson K., Henderson A., Teo S.H., Arun B., Kast K., Dias A., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Eccles D.M., Tricker K., Eyfjord J., Falconer A., Foster C., Gronberg H., Hamdy F.C., Stefansdottir V., Khoo V., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A., Moynihan C., Rennert G., Suri M., Wilson P., Dudderidge T., Offman J., Kote-Jarai Z., Vickers A., Lilja H., Eeles R.A., Helderman van den Enden A.T.J.M., Page E.C., Bancroft E.K., Brook M.N., Assel M., Hassan Al Battat M., Thomas S., Taylor N., Chamberlain A., Pope J., Raghallaigh H.N., Evans D.G., Rothwell J., Maehle L., Grindedal E.M., James P., Mascarenhas L., McKinley J., Side L., Thomas T., van Asperen C., Vasen H., Kiemeney L.A., Ringelberg J., Jensen T.D., Osther P.J.S., Helfand B.T., Genova E., Oldenburg R.A., Cybulski C., Wokolorczyk D., Ong K.-R., Huber C., Lam J., Taylor L., Salinas M., Feliubadalo L., Oosterwijk J.C., van Zelst-Stams W., Cook J., Rosario D.J., Domchek S., Powers J., Buys S., O'Toole K., Ausems M.G.E.M., Schmutzler R.K., Teixeira M.R., Rhiem K., Izatt L., Tripathi V., Cardoso M., Foulkes W.D., Aprikian A., van Randeraad H., Davidson R., Longmuir M., Ruijs M.W.G., Adank M., Williams R., Andrews L., Murphy D.G., Halliday D., Walker L., Liljegren A., Carlsson S., Azzabi A., Jobson I., Morton C., Shackleton K., Snape K., Hanson H., Harris M., Tischkowitz M., Taylor A., Kirk J., Susman R., Chen-Shtoyerman R., Spigelman A., Pachter N., Ahmed M., Ramon y Cajal T., Zgajnar J., Brewer C., Gadea N., Brady A.F., van Os T., Gallagher D., Johannsson O., Donaldson A., Barwell J., Nicolai N., Friedman E., Obeid E., Greenhalgh L., Murthy V., Copakova L., Saya S., McGrath J., Cooke P., Ronlund K., Richardson K., Henderson A., Teo S.H., Arun B., Kast K., Dias A., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Eccles D.M., Tricker K., Eyfjord J., Falconer A., Foster C., Gronberg H., Hamdy F.C., Stefansdottir V., Khoo V., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A., Moynihan C., Rennert G., Suri M., Wilson P., Dudderidge T., Offman J., Kote-Jarai Z., Vickers A., Lilja H., Eeles R.A., Helderman van den Enden A.T.J.M., Page E.C., Bancroft E.K., Brook M.N., Assel M., Hassan Al Battat M., Thomas S., Taylor N., Chamberlain A., Pope J., Raghallaigh H.N., Evans D.G., Rothwell J., Maehle L., Grindedal E.M., James P., Mascarenhas L., McKinley J., Side L., Thomas T., van Asperen C., Vasen H., Kiemeney L.A., Ringelberg J., Jensen T.D., Osther P.J.S., Helfand B.T., Genova E., Oldenburg R.A., Cybulski C., Wokolorczyk D., Ong K.-R., Huber C., Lam J., Taylor L., Salinas M., Feliubadalo L., Oosterwijk J.C., van Zelst-Stams W., Cook J., Rosario D.J., Domchek S., Powers J., Buys S., O'Toole K., Ausems M.G.E.M., and Schmutzler R.K.

Abstract

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. Objective(s): To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. Design, setting, and participants: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at

Published
2019

20. Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations

Author

Bancroft, EK, Saya, S, Page, EC, Myhill, K, Thomas, S, Pope, J, Chamberlain, A, Hart, R, Glover, W, Cook, J, Rosario, DJ, Helfand, BT, Selkirk, CH, Davidson, R, Longmuir, M, Eccles, DM, Gadea, N, Brewer, C, Barwell, J, Salinas, M, Greenhalgh, L, Tischkowitz, M, Henderson, A, Evans, DG, Buys, SS, Eeles, RA, Aaronson, NK, Eeles, R, Bancroft, E, Page, E, Kote-Jarai, Z, Ardern-Jones, A, Bangma, C, Castro, E, Dearnaley, D, Falconer, A, Foster, C, Gronberg, H, Hamdy, FC, Johannsson, OT, Khoo, V, Eccles, D, Lilja, H, Evans, G, Eyfjord, J, Lubinski, J, Maehle, L, Mikropoulos, C, Millner, A, Mitra, A, Offman, J, Moynihan, C, Rennert, G, Suri, M, Dias, A, Taylor, N, D'Mello, L, James, P, Mitchell, G, Shanley, S, Richardson, K, McKinley, J, Petelin, L, Murphy, M, Mascarenhas, L, Murphy, D, Lam, J, Taylor, L, Miller, C, Stapleton, A, Chong, M, Suthers, G, Poplawski, N, Tucker, K, Andrews, L, Duffy, J, Millard, R, Ward, R, Williams, R, Stricker, P, Kirk, J, Bowman, M, Patel, M, Harris, M, O'Connell, S, Hunt, C, Smyth, C, Frydenberg, M, Lindeman, G, Shackleton, K, Morton, C, Susman, R, McGaughran, J, Boon, M, Pachter, N, Townshend, S, Schofield, L, Nicholls, C, Spigelman, A, Gleeson, M, Amor, D, Burke, J, Patterson, B, Swindle, P, Scott, R, Foulkes, W, Boshari, T, Aprikian, A, Jensen, T, Bojeson, A, Osther, P, Skytte, A-B, Cruger, D, Tondering, MK, Gerdes, A-M, Schmutzler, R, Rhiem, K, Wihler, P, Kast, K, Griebsch, C, Johannsson, O, Stefansdottir, V, Murthy, V, Sarin, R, Awatagiri, K, Ghonge, S, Kowtal, P, Mulgund, G, Gallagher, D, Bambury, R, Farrell, M, Gallagher, F, Kiernan, I, Friedman, E, Chen-Shtoyerman, R, Basevitch, A, Leibovici, D, Melzer, E, Ben-Yehoshua, SJ, Nicolai, N, Radice, P, Valdagni, R, Magnani, T, Gay, S, Teo, SH, Tan, HM, Yoon, S-Y, Thong, MK, Vasen, H, Ringleberg, J, van Asperen, C, Kiemeney, B, van Zelst-Stams, W, Ausems, MGEM, van der Luijt, RB, van Os, T, Ruijs, MWG, Adank, MA, Oldenburg, RA, Helderman-van den Enden, APTJM, Caanen, BAH, Oosterwijk, JC, Moller, P, Brennhovd, B, Medvik, H, Hanslien, E, Grindedal, EM, Cybulski, C, Wokolorczyk, D, Teixeira, M, Maia, S, Peixoto, A, Henrique, R, Oliveira, J, Goncalves, N, Araujo, L, Seixas, M, Souto, JP, Nogueira, P, Copakova, L, Zgajnar, J, Krajc, M, Vrecar, A, Capella, G, Ramon y Cajal, T, Fisas, D, Mora, J, Esquena, S, Balmana, J, Morote, J, Liljegren, A, Hjalm-Eriksson, M, Ekdahl, K-J, Carlsson, S, George, A, Kemp, Z, Wiggins, J, Moss, C, Van As, N, Thompson, A, Ogden, C, Woodhouse, C, Kumar, P, Bulman, B, Rothwell, J, Tricker, K, Wise, G, Mercer, C, McBride, D, Costello, P, Pearce, A, Torokwa, A, Paterson, J, Clowes, V, Taylor, A, Newcombe, B, Walker, L, Halliday, D, Stayner, B, Fleming-Brown, D, Snape, K, Hanson, H, Hodgson, S, Brice, G, Homfray, T, Hammond, C, Kohut, K, Anjum, U, Dearing, A, Mencias, M, Potter, A, Renton, C, Searle, A, Hill, K, Goodman, S, Garcia, L, Devlin, G, Everest, S, Nadolski, M, Douglas, F, Jobson, I, Paez, E, Donaldson, A, Tomkins, S, Langman, C, Jacobs, C, Pichert, G, Shaw, A, Kulkarni, A, Tripathi, V, Rose, S, Compton, C, Watson, M, Reinholtz, C, Brady, A, Dorkins, H, Melville, A, Kosicka-Slawinska, M, Cummings, C, Kiesel, V, Bartlett, M, Randhawa, K, Ellery, N, Side, L, Male, A, Simon, K, Rees, K, Tidey, L, Gurasashvili, J, Nevitt, L, Ingram, S, Howell, A, Rosario, D, Catto, J, Howson, J, Ong, K-R, Chapman, C, Cole, T, Heaton, T, Hoffman, J, Burgess, L, Huber, C, Islam, F, Watt, C, Duncan, A, Kockelbergh, R, Mzazi, S, Dineen, A, Sattar, A, Kaemba, B, Sidat, Z, Patel, N, Siguake, K, Birt, A, Poultney, U, Umez-Eronini, N, Mom, J, Sutton, V, Cornford, P, Bermingham, N, Yesildag, P, Treherne, K, Griffiths, J, Cogley, L, Gott, H, Rubinstein, WS, Hulick, P, McGuire, M, Shevrin, D, Kaul, K, Weissman, S, Newlin, A, Vogel, K, Weiss, S, Hook, N, Buys, S, Goldgar, D, Conner, T, Venne, V, Stephenson, R, Dechet, C, Domchek, S, Powers, J, Rustgi, N, Strom, S, Arun, B, Davis, JW, Yamamura, Y, Obeid, E, Giri, V, Gross, L, Bealin, L, Cooney, K, Stoffel, E, Okoth, L, Bancroft, EK, Saya, S, Page, EC, Myhill, K, Thomas, S, Pope, J, Chamberlain, A, Hart, R, Glover, W, Cook, J, Rosario, DJ, Helfand, BT, Selkirk, CH, Davidson, R, Longmuir, M, Eccles, DM, Gadea, N, Brewer, C, Barwell, J, Salinas, M, Greenhalgh, L, Tischkowitz, M, Henderson, A, Evans, DG, Buys, SS, Eeles, RA, Aaronson, NK, Eeles, R, Bancroft, E, Page, E, Kote-Jarai, Z, Ardern-Jones, A, Bangma, C, Castro, E, Dearnaley, D, Falconer, A, Foster, C, Gronberg, H, Hamdy, FC, Johannsson, OT, Khoo, V, Eccles, D, Lilja, H, Evans, G, Eyfjord, J, Lubinski, J, Maehle, L, Mikropoulos, C, Millner, A, Mitra, A, Offman, J, Moynihan, C, Rennert, G, Suri, M, Dias, A, Taylor, N, D'Mello, L, James, P, Mitchell, G, Shanley, S, Richardson, K, McKinley, J, Petelin, L, Murphy, M, Mascarenhas, L, Murphy, D, Lam, J, Taylor, L, Miller, C, Stapleton, A, Chong, M, Suthers, G, Poplawski, N, Tucker, K, Andrews, L, Duffy, J, Millard, R, Ward, R, Williams, R, Stricker, P, Kirk, J, Bowman, M, Patel, M, Harris, M, O'Connell, S, Hunt, C, Smyth, C, Frydenberg, M, Lindeman, G, Shackleton, K, Morton, C, Susman, R, McGaughran, J, Boon, M, Pachter, N, Townshend, S, Schofield, L, Nicholls, C, Spigelman, A, Gleeson, M, Amor, D, Burke, J, Patterson, B, Swindle, P, Scott, R, Foulkes, W, Boshari, T, Aprikian, A, Jensen, T, Bojeson, A, Osther, P, Skytte, A-B, Cruger, D, Tondering, MK, Gerdes, A-M, Schmutzler, R, Rhiem, K, Wihler, P, Kast, K, Griebsch, C, Johannsson, O, Stefansdottir, V, Murthy, V, Sarin, R, Awatagiri, K, Ghonge, S, Kowtal, P, Mulgund, G, Gallagher, D, Bambury, R, Farrell, M, Gallagher, F, Kiernan, I, Friedman, E, Chen-Shtoyerman, R, Basevitch, A, Leibovici, D, Melzer, E, Ben-Yehoshua, SJ, Nicolai, N, Radice, P, Valdagni, R, Magnani, T, Gay, S, Teo, SH, Tan, HM, Yoon, S-Y, Thong, MK, Vasen, H, Ringleberg, J, van Asperen, C, Kiemeney, B, van Zelst-Stams, W, Ausems, MGEM, van der Luijt, RB, van Os, T, Ruijs, MWG, Adank, MA, Oldenburg, RA, Helderman-van den Enden, APTJM, Caanen, BAH, Oosterwijk, JC, Moller, P, Brennhovd, B, Medvik, H, Hanslien, E, Grindedal, EM, Cybulski, C, Wokolorczyk, D, Teixeira, M, Maia, S, Peixoto, A, Henrique, R, Oliveira, J, Goncalves, N, Araujo, L, Seixas, M, Souto, JP, Nogueira, P, Copakova, L, Zgajnar, J, Krajc, M, Vrecar, A, Capella, G, Ramon y Cajal, T, Fisas, D, Mora, J, Esquena, S, Balmana, J, Morote, J, Liljegren, A, Hjalm-Eriksson, M, Ekdahl, K-J, Carlsson, S, George, A, Kemp, Z, Wiggins, J, Moss, C, Van As, N, Thompson, A, Ogden, C, Woodhouse, C, Kumar, P, Bulman, B, Rothwell, J, Tricker, K, Wise, G, Mercer, C, McBride, D, Costello, P, Pearce, A, Torokwa, A, Paterson, J, Clowes, V, Taylor, A, Newcombe, B, Walker, L, Halliday, D, Stayner, B, Fleming-Brown, D, Snape, K, Hanson, H, Hodgson, S, Brice, G, Homfray, T, Hammond, C, Kohut, K, Anjum, U, Dearing, A, Mencias, M, Potter, A, Renton, C, Searle, A, Hill, K, Goodman, S, Garcia, L, Devlin, G, Everest, S, Nadolski, M, Douglas, F, Jobson, I, Paez, E, Donaldson, A, Tomkins, S, Langman, C, Jacobs, C, Pichert, G, Shaw, A, Kulkarni, A, Tripathi, V, Rose, S, Compton, C, Watson, M, Reinholtz, C, Brady, A, Dorkins, H, Melville, A, Kosicka-Slawinska, M, Cummings, C, Kiesel, V, Bartlett, M, Randhawa, K, Ellery, N, Side, L, Male, A, Simon, K, Rees, K, Tidey, L, Gurasashvili, J, Nevitt, L, Ingram, S, Howell, A, Rosario, D, Catto, J, Howson, J, Ong, K-R, Chapman, C, Cole, T, Heaton, T, Hoffman, J, Burgess, L, Huber, C, Islam, F, Watt, C, Duncan, A, Kockelbergh, R, Mzazi, S, Dineen, A, Sattar, A, Kaemba, B, Sidat, Z, Patel, N, Siguake, K, Birt, A, Poultney, U, Umez-Eronini, N, Mom, J, Sutton, V, Cornford, P, Bermingham, N, Yesildag, P, Treherne, K, Griffiths, J, Cogley, L, Gott, H, Rubinstein, WS, Hulick, P, McGuire, M, Shevrin, D, Kaul, K, Weissman, S, Newlin, A, Vogel, K, Weiss, S, Hook, N, Buys, S, Goldgar, D, Conner, T, Venne, V, Stephenson, R, Dechet, C, Domchek, S, Powers, J, Rustgi, N, Strom, S, Arun, B, Davis, JW, Yamamura, Y, Obeid, E, Giri, V, Gross, L, Bealin, L, Cooney, K, Stoffel, E, and Okoth, L

Abstract

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support t

Published
2019

21. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

Author

Page, EC, Bancroft, EK, Brook, MN, Assel, M, Al Battat, MH, Thomas, S, Taylor, N, Chamberlain, A, Pope, J, Ni Raghallaigh, H, Evans, DG, Rothwell, J, Maehle, L, Grindedal, EM, James, P, Mascarenhas, L, McKinley, J, Side, L, Thomas, T, van Asperen, C, Vasen, H, Kiemeney, LA, Ringelberg, J, Jensen, TD, Osther, PJS, Helfand, BT, Genova, E, Oldenburg, RA, Cybulski, C, Wokolorczyk, D, Ong, K-R, Huber, C, Lam, J, Taylor, L, Salinas, M, Feliubadalo, L, Oosterwijk, JC, van Zelst-Stams, W, Cook, J, Rosario, DJ, Domchek, S, Powers, J, Buys, S, O'Toole, K, Ausems, MGEM, Schmutzler, RK, Rhiem, K, Izatt, L, Tripathi, V, Teixeira, MR, Cardoso, M, Foulkes, WD, Aprikian, A, van Randeraad, H, Davidson, R, Longmuir, M, Ruijs, MWG, Helderman van den Enden, ATJM, Adank, M, Williams, R, Andrews, L, Murphy, DG, Halliday, D, Walker, L, Liljegren, A, Carlsson, S, Azzabi, A, Jobson, I, Morton, C, Shackleton, K, Snape, K, Hanson, H, Harris, M, Tischkowitz, M, Taylor, A, Kirk, J, Susman, R, Chen-Shtoyerman, R, Spigelman, A, Pachter, N, Ahmed, M, Ramon y Cajal, T, Zgajnar, J, Brewer, C, Gadea, N, Brady, AF, van Os, T, Gallagher, D, Johannsson, O, Donaldson, A, Barwell, J, Nicolai, N, Friedman, E, Obeid, E, Greenhalgh, L, Murthy, V, Copakova, L, Saya, S, McGrath, J, Cooke, P, Ronlund, K, Richardson, K, Henderson, A, Teo, SH, Arun, B, Kast, K, Dias, A, Aaronson, NK, Ardern-Jones, A, Bangma, CH, Castro, E, Dearnaley, D, Eccles, DM, Tricker, K, Eyfjord, J, Falconer, A, Foster, C, Gronberg, H, Hamdy, FC, Stefansdottir, V, Khoo, V, Lindeman, GJ, Lubinski, J, Axcrona, K, Mikropoulos, C, Mitra, A, Moynihan, C, Rennert, G, Suri, M, Wilson, P, Dudderidge, T, Offman, J, Kote-Jarai, Z, Vickers, A, Lilja, H, Eeles, RA, Page, EC, Bancroft, EK, Brook, MN, Assel, M, Al Battat, MH, Thomas, S, Taylor, N, Chamberlain, A, Pope, J, Ni Raghallaigh, H, Evans, DG, Rothwell, J, Maehle, L, Grindedal, EM, James, P, Mascarenhas, L, McKinley, J, Side, L, Thomas, T, van Asperen, C, Vasen, H, Kiemeney, LA, Ringelberg, J, Jensen, TD, Osther, PJS, Helfand, BT, Genova, E, Oldenburg, RA, Cybulski, C, Wokolorczyk, D, Ong, K-R, Huber, C, Lam, J, Taylor, L, Salinas, M, Feliubadalo, L, Oosterwijk, JC, van Zelst-Stams, W, Cook, J, Rosario, DJ, Domchek, S, Powers, J, Buys, S, O'Toole, K, Ausems, MGEM, Schmutzler, RK, Rhiem, K, Izatt, L, Tripathi, V, Teixeira, MR, Cardoso, M, Foulkes, WD, Aprikian, A, van Randeraad, H, Davidson, R, Longmuir, M, Ruijs, MWG, Helderman van den Enden, ATJM, Adank, M, Williams, R, Andrews, L, Murphy, DG, Halliday, D, Walker, L, Liljegren, A, Carlsson, S, Azzabi, A, Jobson, I, Morton, C, Shackleton, K, Snape, K, Hanson, H, Harris, M, Tischkowitz, M, Taylor, A, Kirk, J, Susman, R, Chen-Shtoyerman, R, Spigelman, A, Pachter, N, Ahmed, M, Ramon y Cajal, T, Zgajnar, J, Brewer, C, Gadea, N, Brady, AF, van Os, T, Gallagher, D, Johannsson, O, Donaldson, A, Barwell, J, Nicolai, N, Friedman, E, Obeid, E, Greenhalgh, L, Murthy, V, Copakova, L, Saya, S, McGrath, J, Cooke, P, Ronlund, K, Richardson, K, Henderson, A, Teo, SH, Arun, B, Kast, K, Dias, A, Aaronson, NK, Ardern-Jones, A, Bangma, CH, Castro, E, Dearnaley, D, Eccles, DM, Tricker, K, Eyfjord, J, Falconer, A, Foster, C, Gronberg, H, Hamdy, FC, Stefansdottir, V, Khoo, V, Lindeman, GJ, Lubinski, J, Axcrona, K, Mikropoulos, C, Mitra, A, Moynihan, C, Rennert, G, Suri, M, Wilson, P, Dudderidge, T, Offman, J, Kote-Jarai, Z, Vickers, A, Lilja, H, and Eeles, RA

Abstract

BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at

Published
2019

24. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition (vol 118, pg 266, 2018)

Author

Mikropoulos, C., Selkirk, C.G.H., Saya, S., Bancroft, E., Vertosick, E., Dadaev, T., Brendler, C., Page, E., Dias, A., Evans, D.G., Rothwell, J., Maehle, L., Axcrona, K., Richardson, K., Eccles, D., Jensen, T., Osther, P.J., Asperen, C.J. van, Vasen, H., Kiemeney, L.A., Ringelberg, J., Cybulski, C., Wokolorczyk, D., Hart, R., Glover, W., Lam, J., Taylor, L., Salinas, M., Feliubadalo, L., Oldenburg, R., Cremers, R., Verhaegh, G., Zelst-Stams, W.A. van, Oosterwijk, J.C., Cook, J., Rosario, D.J., Buys, S.S., Conner, T., Domchek, S., Powers, J., Ausems, M.G.E.M., Teixeira, M.R., Maia, S., Izatt, L., Schmutzler, R., Rhiem, K., Foulkes, W.D., Boshari, T., Davidson, R., Ruijs, M., Helderman-van den Enden, A.T.J.M., Andrews, L., Walker, L., Snape, K., Henderson, A., Jobson, I., Lindeman, G.J., Liljegren, A., Harris, M., Adank, M.A., Kirk, J., Taylor, A., Susman, R., Chen-Shtoyerman, R., Pachter, N., Spigelman, A., Side, L., Zgajnar, J., Mora, J., Brewer, C., Gadea, N., Brady, A.F., Gallagher, D., Os, T. van, Donaldson, A., Stefansdottir, V., Barwell, J., James, P.A., Murphy, D., Friedman, E., Nicolai, N., Greenhalgh, L., Obeid, E., Murthy, V., Copakova, L., McGrath, J., Teo, S.H., Strom, S., Kast, K., Leongamornlert, D.A., Chamberlain, A., Pope, J., Newlin, A.C., Aaronson, N., Ardern-Jones, A., Bangma, C., Castro, E., Dearnaley, D., Eyfjord, J., Falconer, A., Foster, C.S., Gronberg, H., Hamdy, F.C., Johannsson, O., Khoo, V., Lubinski, J., Grindedal, E.M., McKinley, J., Shackleton, K., Mitra, A.V., Moynihan, C., Rennert, G., Suri, M., Tricker, K., Moss, S., Kote-Jarai, Z., Vickers, A., Lilja, H., Helfand, B.T., Eeles, R.A., and IMPACT Study Collaborators

Published
2018

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

Author

Mikropoulos, C., Selkirk, C.G.H., Saya, S., Bancroft, E., Vertosick, E., Dadaev, T., Brendler, C., Page, E., Dias, A., Evans, D.G., Rothwell, J., Maehle, L., Axcrona, K., Richardson, K., Eccles, D., Jensen, T., Osther, P.J., Asperen, C.J. van, Vasen, H., Kiemeney, L.A., Ringelberg, J., Cybulski, C., Wokolorczyk, D., Hart, R., Glover, W., Lam, J., Taylor, L., Salinas, M., Feliubadalo, L., Oldenburg, R., Cremers, R., Verhaegh, G., Zelst-Stams, W.A. van, Oosterwijk, J.C., Cook, J., Rosario, D.J., Buys, S.S., Conner, T., Domchek, S., Powers, J., Ausems, M.G.E.M., Teixeira, M.R., Maia, S., Izatt, L., Schmutzler, R., Rhiem, K., Foulkes, W.D., Boshari, T., Davidson, R., Ruijs, M., Helderman-van den Enden, A.T.J.M., Andrews, L., Walker, L., Snape, K., Henderson, A., Jobson, I., Lindeman, G.J., Liljegren, A., Harris, M., Adank, M.A., Kirk, J., Taylor, A., Susman, R., Chen-Shtoyerman, R., Pachter, N., Spigelman, A., Side, L., Zgajnar, J., Mora, J., Brewer, C., Gadea, N., Brady, A.F., Gallagher, D., Os, T. van, Donaldson, A., Stefansdottir, V., Barwell, J., James, P.A., Murphy, D., Friedman, E., Nicolai, N., Greenhalgh, L., Obeid, E., Murthy, V., Copakova, L., McGrath, J., Teo, S.H., Strom, S., Kast, K., Leongamornlert, D.A., Chamberlain, A., Pope, J., Newlin, A.C., Aaronson, N., Ardern-Jones, A., Bangma, C., Castro, E., Dearnaley, D., Eyfjord, J., Falconer, A., Foster, C.S., Gronberg, H., Hamdy, F.C., Johannsson, O., Khoo, V., Lubinski, J., Grindedal, E.M., McKinley, J., Shackleton, K., Mitra, A.V., Moynihan, C., Rennert, G., Suri, M., Tricker, K., Moss, S., Kote-Jarai, Z., Vickers, A., Lilja, H., Helfand, B.T., Eeles, R.A., and IMPACT Study Collaborators

Subjects
predictive model, prostate cancer, BRCA1, urologic and male genital diseases, genetic predisposition, BRCA2, PSA velocity
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 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml(-1), 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

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

Author

Izatt L., Davidson R., Ruijs M., Helderman-Van Den Enden A.T., Andrews L., Walker L., Snape K., Henderson A., Jobson I., Lindeman G.J., Liljegren A., Harris M., Adank M.A., Kirk J., Taylor A., Susman R., Chen-Shtoyerman R., Pachter N., Spigelman A., Side L., Zgajnar J., Mora J., Brewer C., Gadea N., Brady A.F., Gallagher D., Van Os T., Donaldson A., Stefansdottir V., Barwell J., James P.A., Murphy D., Friedman E., Nicolai N., Greenhalgh L., Obeid E., Murthy V., Copakova L., McGrath J., Teo S.-H., Strom S., Kast K., Leongamornlert D.A., Chamberlain A., Pope J., Newlin A.C., Aaronson N., Ardern-Jones A., Bangma C., Castro E., Dearnaley D., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lubinski J., Grindedal E.M., McKinley J., Shackleton K., Mitra A.V., Moynihan C., Rennert G., Suri M., Tricker K., Moss S., Kote-Jarai Z., Vickers A., Lilja H., Helfand B.T., Eeles R.A., Mikropoulos C., Selkirk C.G.H., Saya S., Bancroft E., Vertosick E., Dadaev T., Brendler C., Page E., Dias A., Evans D.G., Rothwell J., Maehle L., Axcrona K., Richardson K., Eccles D., Jensen T., Osther P.J., Van Asperen C.J., Vasen H., Kiemeney L.A., Ringelberg J., Cybulski C., Wokolorczyk D., Hart R., Glover W., Lam J., Taylor L., Salinas M., Feliubadalo L., Oldenburg R., Cremers R., Verhaegh G., Van Zelst-Stams W.A., Oosterwijk J.C., Cook J., Rosario D.J., Buys S.S., Conner T., Domchek S., Powers J., Ausems M.G., Teixeira M.R., Maia S., Schmutzler R., Rhiem K., Foulkes W.D., Boshari T., Izatt L., Davidson R., Ruijs M., Helderman-Van Den Enden A.T., Andrews L., Walker L., Snape K., Henderson A., Jobson I., Lindeman G.J., Liljegren A., Harris M., Adank M.A., Kirk J., Taylor A., Susman R., Chen-Shtoyerman R., Pachter N., Spigelman A., Side L., Zgajnar J., Mora J., Brewer C., Gadea N., Brady A.F., Gallagher D., Van Os T., Donaldson A., Stefansdottir V., Barwell J., James P.A., Murphy D., Friedman E., Nicolai N., Greenhalgh L., Obeid E., Murthy V., Copakova L., McGrath J., Teo S.-H., Strom S., Kast K., Leongamornlert D.A., Chamberlain A., Pope J., Newlin A.C., Aaronson N., Ardern-Jones A., Bangma C., Castro E., Dearnaley D., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lubinski J., Grindedal E.M., McKinley J., Shackleton K., Mitra A.V., Moynihan C., Rennert G., Suri M., Tricker K., Moss S., Kote-Jarai Z., Vickers A., Lilja H., Helfand B.T., Eeles R.A., Mikropoulos C., Selkirk C.G.H., Saya S., Bancroft E., Vertosick E., Dadaev T., Brendler C., Page E., Dias A., Evans D.G., Rothwell J., Maehle L., Axcrona K., Richardson K., Eccles D., Jensen T., Osther P.J., Van Asperen C.J., Vasen H., Kiemeney L.A., Ringelberg J., Cybulski C., Wokolorczyk D., Hart R., Glover W., Lam J., Taylor L., Salinas M., Feliubadalo L., Oldenburg R., Cremers R., Verhaegh G., Van Zelst-Stams W.A., Oosterwijk J.C., Cook J., Rosario D.J., Buys S.S., Conner T., Domchek S., Powers J., Ausems M.G., Teixeira M.R., Maia S., Schmutzler R., Rhiem K., Foulkes W.D., and Boshari T.

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. Method(s):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. Result(s):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. Conclusion(s):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

30. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition (vol 118, pg 266, 2018)

Author

Mikropoulos, C, Selkirk, CGH, Saya, S, Bancroft, E, Vertosick, E, Dadaev, T, Brendler, C, Page, E, Dias, A, Evans, DG, Rothwell, J, Maehle, L, Axcrona, K, Richardson, K, Eccles, D, Jensen, T, Osther, PJ, van Asperen, CJ, Vasen, H, Kiemeney, LA, Ringelberg, J, Cybulski, C, Wokolorczyk, D, Hart, R, Glover, W, Lam, J, Taylor, L, Salinas, M, Feliubadalo, L, Oldenburg, R, Cremers, R, Verhaegh, G, van Zelst-Stams, WA, Oosterwijk, JC, Cook, J, Rosario, DJ, Buys, SS, Conner, T, Domchek, S, Powers, J, Ausems, MGEM, Teixeira, MR, Maia, S, Izatt, L, Schmutzler, R, Rhiem, K, Foulkes, WD, Boshari, T, Davidson, R, Ruijs, M, Helderman-van den Enden, ATJM, Andrews, L, Walker, L, Snape, K, Henderson, A, Jobson, I, Lindeman, GJ, Liljegren, A, Harris, M, Adank, MA, Kirk, J, Taylor, A, Susman, R, Chen-Shtoyerman, R, Pachter, N, Spigelman, A, Side, L, Zgajnar, J, Mora, J, Brewer, C, Gadea, N, Brady, AF, Gallagher, D, van Os, T, Donaldson, A, Stefansdottir, V, Barwell, J, James, PA, Murphy, D, Friedman, E, Nicolai, N, Greenhalgh, L, Obeid, E, Murthy, V, Copakova, L, McGrath, J, Teo, S-H, Strom, S, Kast, K, Leongamornlert, DA, Chamberlain, A, Pope, J, Newlin, AC, Aaronson, N, Ardern-Jones, A, Bangma, C, Castro, E, Dearnaley, D, Eyfjord, J, Falconer, A, Foster, CS, Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lubinski, J, Grindedal, EM, McKinley, J, Shackleton, K, Mitra, AV, Moynihan, C, Rennert, G, Suri, M, Tricker, K, Moss, S, Kote-Jarai, Z, Vickers, A, Lilja, H, Helfand, BT, Eeles, RA, Mikropoulos, C, Selkirk, CGH, Saya, S, Bancroft, E, Vertosick, E, Dadaev, T, Brendler, C, Page, E, Dias, A, Evans, DG, Rothwell, J, Maehle, L, Axcrona, K, Richardson, K, Eccles, D, Jensen, T, Osther, PJ, van Asperen, CJ, Vasen, H, Kiemeney, LA, Ringelberg, J, Cybulski, C, Wokolorczyk, D, Hart, R, Glover, W, Lam, J, Taylor, L, Salinas, M, Feliubadalo, L, Oldenburg, R, Cremers, R, Verhaegh, G, van Zelst-Stams, WA, Oosterwijk, JC, Cook, J, Rosario, DJ, Buys, SS, Conner, T, Domchek, S, Powers, J, Ausems, MGEM, Teixeira, MR, Maia, S, Izatt, L, Schmutzler, R, Rhiem, K, Foulkes, WD, Boshari, T, Davidson, R, Ruijs, M, Helderman-van den Enden, ATJM, Andrews, L, Walker, L, Snape, K, Henderson, A, Jobson, I, Lindeman, GJ, Liljegren, A, Harris, M, Adank, MA, Kirk, J, Taylor, A, Susman, R, Chen-Shtoyerman, R, Pachter, N, Spigelman, A, Side, L, Zgajnar, J, Mora, J, Brewer, C, Gadea, N, Brady, AF, Gallagher, D, van Os, T, Donaldson, A, Stefansdottir, V, Barwell, J, James, PA, Murphy, D, Friedman, E, Nicolai, N, Greenhalgh, L, Obeid, E, Murthy, V, Copakova, L, McGrath, J, Teo, S-H, Strom, S, Kast, K, Leongamornlert, DA, Chamberlain, A, Pope, J, Newlin, AC, Aaronson, N, Ardern-Jones, A, Bangma, C, Castro, E, Dearnaley, D, Eyfjord, J, Falconer, A, Foster, CS, Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lubinski, J, Grindedal, EM, McKinley, J, Shackleton, K, Mitra, AV, Moynihan, C, Rennert, G, Suri, M, Tricker, K, Moss, S, Kote-Jarai, Z, Vickers, A, Lilja, H, Helfand, BT, and Eeles, RA

Abstract

This corrects the article DOI: 10.1038/bjc.2017.429.

Published
2018

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

Author

Mikropoulos, C, Selkirk, CGH, Saya, S, Bancroft, E, Vertosick, E, Dadaev, T, Brendler, C, Page, E, Dias, A, Evans, DG, Rothwell, J, Maehle, L, Axcrona, K, Richardson, K, Eccles, D, Jensen, T, Osther, PJ, van Asperen, CJ, Vasen, H, Kiemeney, LA, Ringelberg, J, Cybulski, C, Wokolorczyk, D, Hart, R, Glover, W, Lam, J (Jan), Taylor, L, Salinas, M, Feliubadalo, L, Oldenburg, Rogier, Cremers, R, Verhaegh, G, van Zelst-Stams, WA, Oosterwijk, JC, Cook, J, Rosario, DJ, Buys, SS, Conner, T, Domchek, S, Powers, J, Ausems, M, Teixeira, MR, Maia, S, Izatt, L, Schmutzler, R, Rhiem, K, Foulkes, WD, Boshari, T, Davidson, R, Ruijs, M, Helderman-van d Enden, A, Andrews, L, Walker, L, Snape, K, Henderson, A, Jobson, I, Lindeman, GJ, Liljegren, A, Harris, M, Adank, MA (Muriel), Kirk, J, Taylor, A, Susman, R, Chen-Shtoyerman, R, Pachter, N, Spigelman, A, Side, L, Zgajnar, J, Mora, J, Brewer, C, Gadea, N, Brady, AF, Gallagher, D, Van Os, T, Donaldson, A, Stefansdottir, V, Barwell, J, James, PA, Murphy, D, Friedman, E, Nicolai, N, Greenhalgh, L, Obeid, E, Murthy, V, Copakova, L, McGrath, J, Teo, SH, Strom, S, Kast, K, Leongamornlert, DA, Chamberlain, A, Pope, J, Newlin, AC, Aaronson, N, Ardern-Jones, A, Bangma, C.H., Castro, E, Dearnaley, D, Eyfjord, J, Falconer, A, Foster, CS (Christopher), Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lubinski, J, Grindedal, EM, McKinley, J, Shackleton, K, Mitra, AV, Moynihan, C, Rennert, G, Suri, M, Tricker, K, Moss, S, Kote-Jarai, Z, Vickers, A, Lilja, H, Helfand, BT, Eeles, RA, Mikropoulos, C, Selkirk, CGH, Saya, S, Bancroft, E, Vertosick, E, Dadaev, T, Brendler, C, Page, E, Dias, A, Evans, DG, Rothwell, J, Maehle, L, Axcrona, K, Richardson, K, Eccles, D, Jensen, T, Osther, PJ, van Asperen, CJ, Vasen, H, Kiemeney, LA, Ringelberg, J, Cybulski, C, Wokolorczyk, D, Hart, R, Glover, W, Lam, J (Jan), Taylor, L, Salinas, M, Feliubadalo, L, Oldenburg, Rogier, Cremers, R, Verhaegh, G, van Zelst-Stams, WA, Oosterwijk, JC, Cook, J, Rosario, DJ, Buys, SS, Conner, T, Domchek, S, Powers, J, Ausems, M, Teixeira, MR, Maia, S, Izatt, L, Schmutzler, R, Rhiem, K, Foulkes, WD, Boshari, T, Davidson, R, Ruijs, M, Helderman-van d Enden, A, Andrews, L, Walker, L, Snape, K, Henderson, A, Jobson, I, Lindeman, GJ, Liljegren, A, Harris, M, Adank, MA (Muriel), Kirk, J, Taylor, A, Susman, R, Chen-Shtoyerman, R, Pachter, N, Spigelman, A, Side, L, Zgajnar, J, Mora, J, Brewer, C, Gadea, N, Brady, AF, Gallagher, D, Van Os, T, Donaldson, A, Stefansdottir, V, Barwell, J, James, PA, Murphy, D, Friedman, E, Nicolai, N, Greenhalgh, L, Obeid, E, Murthy, V, Copakova, L, McGrath, J, Teo, SH, Strom, S, Kast, K, Leongamornlert, DA, Chamberlain, A, Pope, J, Newlin, AC, Aaronson, N, Ardern-Jones, A, Bangma, C.H., Castro, E, Dearnaley, D, Eyfjord, J, Falconer, A, Foster, CS (Christopher), Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lubinski, J, Grindedal, EM, McKinley, J, Shackleton, K, Mitra, AV, Moynihan, C, Rennert, G, Suri, M, Tricker, K, Moss, S, Kote-Jarai, Z, Vickers, A, Lilja, H, Helfand, BT, and Eeles, RA

Published
2018

32. Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls

Author

Saya, S, Killick, E, Thomas, S, Taylor, N, Bancroft, EK, Rothwell, J, Benafif, S, Dias, A, Mikropoulos, C, Pope, J, Chamberlain, A, Gunapala, R, SIGNIFY Study Steering Committee, Izatt, L, Side, L, Walker, L, Tomkins, S, Cook, J, Barwell, J, Wiles, V, Limb, L, Eccles, D, Leach, MO, Shanley, S, Gilbert, FJ, Hanson, H, Gallagher, D, Rajashanker, B, Whitehouse, RW, Koh, D-M, Sohaib, SA, Evans, DG, Eeles, RA, Gilbert, Fiona [0000-0002-0124-9962], and Apollo - University of Cambridge Repository

Subjects
Li Fraumeni syndrome, Whole body MRI, Screening, TP53 mutation carriers, Controls
Abstract

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.

Published
2017

33. Clinical utility of complex multi-platform profiling in metastatic cancer patients

Author

Garcia Foncillas, J., primary, Aftimos, P.G., additional, Barthelemy, P., additional, Bellmunt, J., additional, Berchem, G., additional, Camps, C., additional, de las Peñas, R., additional, Finzel, A., additional, Hervonen, J.P., additional, Joensuu, T., additional, Kong, A., additional, Mackay, J., additional, Mikropoulos, C., additional, Mokbel, K., additional, Mouysset, J.-L., additional, Perren, T.-J., additional, Guitti, G., additional, and Laes, J.-F., additional

Published
2018
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36. The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer

Author

Castro, E, Mikropoulos, C, Bancroft, EK, Dadaev, T, Goh, C, Taylor, N, Saunders, E, Borley, N, Keating, D, Page, EC, Saya, S, Hazell, S, Livni, N, deSouza, N, Neal, D, Hamdy, FC, Kumar, P, Antoniou, AC, Kote-Jarai, Z, Eeles, RA, Castro, E, Mikropoulos, C, Bancroft, EK, Dadaev, T, Goh, C, Taylor, N, Saunders, E, Borley, N, Keating, D, Page, EC, Saya, S, Hazell, S, Livni, N, deSouza, N, Neal, D, Hamdy, FC, Kumar, P, Antoniou, AC, Kote-Jarai, Z, and Eeles, RA

Abstract

BACKGROUND: A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. PATIENTS AND METHODS: A total of 100 men aged 40-69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. RESULTS: Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). CONCLUSION: The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progre

Published
2016

39. The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers

Author

Cremers, R.G.H.M. (Ruben), Eeles, R. (Rosalind), Bancroft, E.K. (Elizabeth), Ringelberg-Borsboom, J. (Janneke), Vasen, H. (Hans), Asperen, C.J. (Christi) van, Schalken, J.A. (Jack), Verhaegh, G. (Gerald), Kiemeney, L.A.L.M. (Bart), Aaronson, N.K. (Neil), Ardem-Jones, A., Bangma, C.H. (Chris), Castro, E. (Elena), Dearnaley, D. (David), Eccles, D. (Diana), Evans, D.G. (Gareth), Eyfjord, J., Falconer, A., Foster, C.S. (Christopher), Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johansson, O., Khoo, V., Kote-Jarai, Z., Lilja, H. (Hans), Lubinski, J. (Jan), Maehle, L., Melia, J., Mikropoulos, C., Mitchell, G. (Gillian), Mitra, A. (Anita), Moss, S.M. (Sue), Moynihan, C., Page, E. (Elizabeth), Rennert, G. (Gad), Suri, M. (Mohnish), Wilson, P., Cremers, R.G.H.M. (Ruben), Eeles, R. (Rosalind), Bancroft, E.K. (Elizabeth), Ringelberg-Borsboom, J. (Janneke), Vasen, H. (Hans), Asperen, C.J. (Christi) van, Schalken, J.A. (Jack), Verhaegh, G. (Gerald), Kiemeney, L.A.L.M. (Bart), Aaronson, N.K. (Neil), Ardem-Jones, A., Bangma, C.H. (Chris), Castro, E. (Elena), Dearnaley, D. (David), Eccles, D. (Diana), Evans, D.G. (Gareth), Eyfjord, J., Falconer, A., Foster, C.S. (Christopher), Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johansson, O., Khoo, V., Kote-Jarai, Z., Lilja, H. (Hans), Lubinski, J. (Jan), Maehle, L., Melia, J., Mikropoulos, C., Mitchell, G. (Gillian), Mitra, A. (Anita), Moss, S.M. (Sue), Moynihan, C., Page, E. (Elizabeth), Rennert, G. (Gad), Suri, M. (Mohnish), and Wilson, P.

Abstract

Objective: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. Materials and methods: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level≥3.0. ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate biopsies and (2) as an indicator for prostate biopsies among men with an elevated P

Published
2015
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40. The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers

Author

Cremers, R, Eeles, RA, Bancroft, EK, Ringelberg, J, Vasen, HF, van Asperen, CJ, Schalken, JA, Verhaegh, GW, Kiemeney, LA, Aaronson, N, Ardem-Jones, A, Bangma, C.H., Castro, E, Dearnaley, D, Eccles, D, Evans, DGR, Eyfjord, J, Falconer, A, Foster, CS (Christopher), Gronberg, H, Hamdy, FC, Johansson, O, Khoo, V, Kote-Jarai, Z, Lija, H, Lubinski, J, Maehle, L, Melia, J, Mikropoulos, C, Mitchell, G, Mitra, AV, Moss, S, Moynihan, C, Page, EC, Rennert, G, Suri, M, Wilson, P, Cremers, R, Eeles, RA, Bancroft, EK, Ringelberg, J, Vasen, HF, van Asperen, CJ, Schalken, JA, Verhaegh, GW, Kiemeney, LA, Aaronson, N, Ardem-Jones, A, Bangma, C.H., Castro, E, Dearnaley, D, Eccles, D, Evans, DGR, Eyfjord, J, Falconer, A, Foster, CS (Christopher), Gronberg, H, Hamdy, FC, Johansson, O, Khoo, V, Kote-Jarai, Z, Lija, H, Lubinski, J, Maehle, L, Melia, J, Mikropoulos, C, Mitchell, G, Mitra, AV, Moss, S, Moynihan, C, Page, EC, Rennert, G, Suri, M, and Wilson, P

Published
2015

43. 2574 Prostate-Specific Antigen velocity as a predictive biomarker in a prospective prostate cancer screening study of men with genetic predisposition

Author

Selkirk, C., primary, Mikropoulos, C., additional, Saya, S., additional, Bancroft, E., additional, Dadaev, T., additional, Brendler, C., additional, Page, E., additional, Leongamornlert, D., additional, Taylor, N., additional, Saunders, E., additional, Cieza-Borrela, C., additional, Teixeira Dias, A.E., additional, Moss, S., additional, Kote-Jarai, Z., additional, Helfand, B., additional, and Eeles, R., additional

Published
2015
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44. Prevalence of theHOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes

Author

Kote-Jarai, Z., primary, Mikropoulos, C., additional, Leongamornlert, D.A., additional, Dadaev, T., additional, Tymrakiewicz, M., additional, Saunders, E.J., additional, Jones, M., additional, Jugurnauth-Little, S., additional, Govindasami, K., additional, Guy, M., additional, Hamdy, F.C., additional, Donovan, J.L., additional, Neal, D.E., additional, Lane, J.A., additional, Dearnaley, D., additional, Wilkinson, R.A., additional, Sawyer, E.J., additional, Morgan, A., additional, Antoniou, A.C., additional, Eeles, R.A., additional, Hall, Per, additional, Berchuck, Andrew, additional, Dennis, Joe, additional, Dunning, Alison M., additional, Lee, Andrew, additional, Dicks, Ed, additional, Simard, Jacques, additional, Tessier, Daniel C., additional, Bacot, Francois, additional, Vincent, Daniel, additional, LaBoissière, Sylvie, additional, Robidoux, Frederic, additional, Bojesen, Stig E., additional, Nielsen, Sune F., additional, and Nordestgaard, Borge G., additional

Published
2015
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45. Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer

Author

Gibson, G, Saunders, EJ, Dadaev, T, Leongamornlert, DA, Jugurnauth-Little, S, Tymrakiewicz, M, Wiklund, F, Al Olama, AA, Benlloch, S, Neal, DE, Hamdy, FC, Donovan, JL, Giles, GG, Severi, G, Gronberg, H, Aly, M, Haiman, CA, Schumacher, F, Henderson, BE, Lindstrom, S, Kraft, P, Hunter, DJ, Gapstur, S, Chanock, S, Berndt, SI, Albanes, D, Andriole, G, Schleutker, J, Weischer, M, Nordestgaard, BG, Canzian, F, Campa, D, Riboli, E, Key, TJ, Travis, RC, Ingles, SA, John, EM, Hayes, RB, Pharoah, P, Khaw, K-T, Stanford, JL, Ostrander, EA, Signorello, LB, Thibodeau, SN, Schaid, D, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, JY, Kaneva, R, Batra, J, Clements, JA, Teixeira, MR, Xu, J, Mikropoulos, C, Goh, C, Govindasami, K, Guy, M, Wilkinson, RA, Sawyer, EJ, Morgan, A, Easton, DF, Muir, K, Eeles, RA, Kote-Jarai, Z, Gibson, G, Saunders, EJ, Dadaev, T, Leongamornlert, DA, Jugurnauth-Little, S, Tymrakiewicz, M, Wiklund, F, Al Olama, AA, Benlloch, S, Neal, DE, Hamdy, FC, Donovan, JL, Giles, GG, Severi, G, Gronberg, H, Aly, M, Haiman, CA, Schumacher, F, Henderson, BE, Lindstrom, S, Kraft, P, Hunter, DJ, Gapstur, S, Chanock, S, Berndt, SI, Albanes, D, Andriole, G, Schleutker, J, Weischer, M, Nordestgaard, BG, Canzian, F, Campa, D, Riboli, E, Key, TJ, Travis, RC, Ingles, SA, John, EM, Hayes, RB, Pharoah, P, Khaw, K-T, Stanford, JL, Ostrander, EA, Signorello, LB, Thibodeau, SN, Schaid, D, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, JY, Kaneva, R, Batra, J, Clements, JA, Teixeira, MR, Xu, J, Mikropoulos, C, Goh, C, Govindasami, K, Guy, M, Wilkinson, RA, Sawyer, EJ, Morgan, A, Easton, DF, Muir, K, Eeles, RA, and Kote-Jarai, Z

Abstract

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Published
2014

46. Prevalence of Hoxb13G84E Germline Mutation in Uk Prostate Cancer Cases; Correlation with Tumour Characteristics and Outcomes

Author

Mikropoulos, C., primary, Dadaev, T., additional, Tymrakiewicz, M., additional, Leongamornlert, D., additional, Saunders, E., additional, Little, S.J., additional, Govindasami, K., additional, Guy, M., additional, Wilkinson, R., additional, Morgan, A., additional, Donovan, J., additional, Neal, D., additional, Hamdy, F., additional, Antoniou, A., additional, Eeles, R., additional, and Kote-Jarai, Z., additional

Published
2014
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