Abstract
IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international collaboration investigating the utility of targeted prostate-specific antigen (PSA) screening for men at increased risk of prostate cancer due to inherited predisposition. Although the majority of prostate cancer occurs sporadically, it is recognized that family history plays a role in a significant number of cases: a family history either of prostate cancer alone [1], or of other cancers including breast and ovarian cancer [2]. Evidence of the link between single genes and prostate cancer risk is strongest for the BRCA1 and BRCA2 genes [3-5], with BRCA2 in particular thought to lead to a relative risk of 4.65 (95% CI 3.48-6.22). This relative risk may be as high as 7.33 in men under the age of 65 years. Population prostate cancer screening remains controversial because of the potential for detection of clinically insignificant disease in young men and the risk of over-treatment. There is increasing interest and concern in European countries about whether prostate cancer screening should be offered to the general population and whether this would lead to a reduction in mortality from prostate cancer. IMPACT raises the hypothesis that targeting screening at the men in the population who are known to have an increased risk of the disease might improve the effectiveness of prostate cancer screening. Beginning with a pilot of 100 patients, the IMPACT study ultimately aims to recruit a total of 850 carriers of mutations in BRCA1 and BRCA2 and 850 controls (men shown not to carry familial BRCA1/2 mutations by predictive genetic testing). Recruitment will be open for five years, followed by five years of follow-up. In 2005, a project known as AIDIT (Advancing International co-operation and Developing Infrastructure for Targeted screening of prostate cancer in men with genetic predisposition) was awarded funding through the EC Framework 6 Programme as part of an endeavour to reduce research fragmentation and duplication, and to facilitate research collaboration across Europe. IMPACT currently includes collaborators from 24 countries. AIDIT's aim is to expand the IMPACT consortium within the associated candidate countries (ACCs) and new member states of the EU. The expansion of IMPACT is likely to benefit both the study and the research teams: a higher number of collaborating centres will allow access to a larger number of men at risk, making it possible to recruit as many carriers as are needed for the study, particularly in populations likely to harbour founder mutations; and for all collaborators - both new and existing - it is hoped that participation in AIDIT and IMPACT will foster an environment of ongoing interaction and learning.
Highlights
IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international collaboration investigating the utility of targeted prostate-specific antigen (PSA) screening for men at increased risk of prostate cancer due to inherited predisposition
Evidence of the link between single genes and prostate cancer risk is strongest for the BRCA1 and BRCA2 genes [3,4,5], with BRCA2 in particular thought to lead to a relative risk of 4.65 (95%CI 3.48-6.22)
IMPACT raises the hypothesis that targeting screening at the men in the population who are known to have an increased risk of the disease might improve the effectiveness of prostate cancer screening
Summary
IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international collaboration investigating the utility of targeted prostate-specific antigen (PSA) screening for men at increased risk of prostate cancer due to inherited predisposition. Evidence of the link between single genes and prostate cancer risk is strongest for the BRCA1 and BRCA2 genes [3,4,5], with BRCA2 in particular thought to lead to a relative risk of 4.65 (95%CI 3.48-6.22). This relative risk may be as high as 7.33 in men under the age of 65 years. IMPACT raises the hypothesis that targeting screening at the men in the population who are known to have an increased risk of the disease might improve the effectiveness of prostate cancer screening. R Doherty, J Lubinski, E Manguoglu, G Luleci, M Christie, P Craven, E Bancroft, A Mitra, S Morgan, R Eeles on behalf of the IMPACT steering committee and collaborators
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