The Center for Medical Genetics has established strong collaborative partnerships in the area of prostate cancer research with outstanding researchers both within the NorthShore University HealthSystem (NorthShore) system and in the broader genetics research community.
The IMPACT Study of Men with BRCA1 and BRCA2 Mutations and Mutation-Negative Controls
Investigators
Study Principal Investigator: Rosalind Eeles, M.A., Ph.D. (Institute of Cancer Research/Royal M.A.rsden NHS Trust, United Kingdom)
NorthShore Principal Investigator: Wendy S. Rubinstein, M.D., Ph.D.
Capsule
Men who carry inherited mutations in the BRCA1 or BRCA2 genes are at increased risk of developing prostate cancer. A blood test measuring Prostate Specific Antigen (PSA) is currently the best method to screen for prostate cancer in the general population. However, the effectiveness of using PSA for screening in the BRCA1 and BRCA2 high-risk population is unknown. The overall study goal is to determine the usefulness of available screening methods in men at high risk and to determine new and more effective ways of screening for prostate cancer. Furthermore, we hope to gain a better understanding of the biological process of prostate cancer in BRCA1 and BRCA2 mutation carriers.
The NorthShore Center for Medical Genetics is collaborating with the Institute of Cancer Research and Royal M.A.rsden Hospital NHS Foundation Trust in the United Kingdom as well as other sites both nationally and internationally. The IMPACT study is one of the research initiatives of the NorthShore Center for Prostate Health.
“IMPACT” stands for:
Identification of Men with a genetic predisposition to ProstAte Cancer:
Targeted Screening in BRCA1/2 mutation carriers and controls
The goal of the international study is to enroll 500 men with BRCA1 mutations, 350 men with BRCA2 mutations and an additional 850 men who have tested negative for known BRCA1 or BRCA2 familial mutations. At NorthShore University HealthSystem, we seek to enroll and study 100 participants.
Study Participant Recruitment & Eligibility
Recruitment open
In order to participate in the IMPACT study, you must be a M.A.le age 40 to 69 years who has a known BRCA1 or BRCA2 mutation in your family.
If you choose to participate you will be asked to come in for an annual visit for 5 years for a blood draw to measure PSA levels and to donate a sample of urine. If your PSA level is found to be raised, a prostate biopsy would be suggested with the potential to discover the occurrence of prostate cancer.
If you have had genetic testing for the BRCA1 or BRCA2 mutation in your family, you M.A.y be eligible whether your test was positive or negative for a mutation. If you do not know your BRCA1 or BRCA2 mutation status, you M.A.y still be eligible to participate. You would be asked to undergo genetic testing for the BRCA1 or BRCA2 mutation that was found in your family. The costs of genetic counseling and genetic testing are covered by the study. You M.A.y choose whether or not to learn the results of your genetic test.
If you are interested in participating in the IMPACT study, please call us for more specific inforM.A.tion at 847-570-4652.
Outcomes
At the time our center entered the study, over 200 men had already been enrolled in the study internationally. The IMPACT pilot results suggest that the PSA screen is effective in BRCA carriers. BRCA carriers with an elevated PSA were more likely than controls to actually have prostate cancer found at biopsy, and they are less likely to undergo a biopsy for an unfounded reason.
Early results suggest that prostate cancer in BRCA1 and BRCA2 carriers M.A.y be more aggressive and carry a poorer prognosis. Mutation carriers appear to be more likely than controls to have high Gleason scores (a pathology grading system) of 8, 9, or 10, reflecting more aggressive behavior of prostate cancer.
Publications
Whitaker HC, Kote-Jarai Z, Ross-Adams H, Warren AY, Burge J, George A, Bancroft E, Jhavar S, Leongamornlert D, Tymrakiewicz M, Saunders E, Page E, Mitra A, Mitchell G, LindeM.A.n GJ, Evans DG, Blanco I, Mercer C, Rubinstein WS, Clowes V, Douglas F, Hodgson S, Walker L, Donaldson A, Izatt L, Dorkins H, M.A.le A, Tucker K, Stapleton A, Lam J, Kirk J, Lilja H, Easton D; IMPACT Study Steering Committee; IMPACT Study Collaborators; UK GPCS Collaborators, Cooper C, Eeles R, Neal DE. The rs10993994 Risk Allele for Prostate Cancer Results in Clinically Relevant Changes in Microseminoprotein-Beta Expression in Tissue and Urine. PLoS ONE, 2010; 5(10): e13363.
Mitra A, Fisher C, Foster CS, Jameson C, Barbachano Y, Bartlett J, Bancroft E, Doherty R, Kote-Jari Z, Peock S, Easton D, The IMPACT and EMBRACE Collaborators and Eeles R. Prostate cancer in M.A.le BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype. British Journal of Cancer. 2008; 98(2): 502-507.
Mitra AR, Bancroft EK, Eeles RA, on behalf of the IMPACT Steering Committee and Collaborators. A review of targeted screening for prostate cancer: introducing the IMPACT Study. British Journal of Urology International. 2007; 99: 1350-1355.
Morgan S, Lubinski J, M.A.nguolu E, Luleci G, Doherty R, Christie M, Craven P, Bancroft E, Mitra A, Zieba K, Eeles R, on behalf of the IMPACT steering committee and IMPACT collaborators. IMPACT and AIDIT: Strengthening Research Ties in Eastern Europe. Hereditary Cancer in Clinical Practice. 2006; 4(2): 111-112.
Edwards SM, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, Jackson R, Southgate C, Singh R, Falconer A, Dearnaley DP, Ardern-Jones A, Murkin A, Dowe A, Kelly J, Williams S, Oram R, Stevens M, Teare DM, Ponder BAJ, Gayther SA, The Cancer Research UK/British Prostate Group UK Familial Prostate Study Collaborators, British Association of Urological Surgeons Section of Oncology, Easton DF, Eeles, RA. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. America Journal of HuM.A.n Genetics. 2003; 72:1-12.
Eeles RA, The UK Familial Prostate Study Co-ordinating Group & the CRC/BPG UK Familial Prostate Cancer Study Collaborators. Genetic predisposition to prostate cancer. Prostate Cancer and Prostatic Disease. 1999; 2: 9-15.