DEVELOPMENT OF NETWORK DEVELOPMENT OF NETWORK OF CANCER FAMILY SYNDROME OF CANCER FAMILY SYNDROME

REGISTRIES IN EASTERN EUROPEREGISTRIES IN EASTERN EUROPE

Project co-ordinator: Project co-ordinator: Prof. Jan LubiProf. Jan Lubińńskiski

Hereditary Cancer Centre, Hereditary Cancer Centre, Pomeranian MedicPomeranian Medical Universityal University, Szczecin, Poland, Szczecin, Poland

NETWORK OF CANCER FAMILY SYNDROME NETWORK OF CANCER FAMILY SYNDROME REGISTERS IN EASTERN EUROPEREGISTERS IN EASTERN EUROPE

EU PROJECTEU PROJECT

PROJECT PARTICIPANTS:PROJECT PARTICIPANTS: Prof. P. Boesze Prof. P. Boesze (Hungary), (Hungary), Dr. P. Elsakov Dr. P. Elsakov (Lithuania), (Lithuania), Dr. L. Foretova Dr. L. Foretova (Czech Republic), (Czech Republic), Prof. J. Gardovskis Prof. J. Gardovskis (Latvia), (Latvia), Prof. N. Haites Prof. N. Haites (United Kingdom), (United Kingdom), Dr. G. Moeslein Dr. G. Moeslein (Germany), (Germany), Prof. H. Neumann Prof. H. Neumann (Germany), (Germany), Prof. B. Ponder Prof. B. Ponder (United Kingdom), (United Kingdom), Prof. H. Sobol Prof. H. Sobol (France), (France), Dr. H. Vasen Dr. H. Vasen (Netherlands), (Netherlands), Dr. W. Weber Dr. W. Weber (Switzerland), (Switzerland), J.-P. Mecklin J.-P. Mecklin (Finnland – subcontractor)(Finnland – subcontractor)

THE SCIENTIFIC OBJECTIVES THE SCIENTIFIC OBJECTIVES OF THE PROJECT INCLUDED:OF THE PROJECT INCLUDED:

1.1. Elaboration of standards for a model cancer family Elaboration of standards for a model cancer family syndrome (CFS) registries in Eastern Europesyndrome (CFS) registries in Eastern Europe

2.2. Registration of 2000 families with different types of CFS Registration of 2000 families with different types of CFS in populations of East European countries (Czech Republic, in populations of East European countries (Czech Republic, Hungary, Latvia, Lithuania, Poland)Hungary, Latvia, Lithuania, Poland)

3.3. Initiation of European collaborative studies with the use Initiation of European collaborative studies with the use of material collected by East European CFS registriesof material collected by East European CFS registries

RESULTS:RESULTS:Ad 1.Ad 1.

In the initial phase of the project, East European In the initial phase of the project, East European scientists visited Western centres in United Kingdom, scientists visited Western centres in United Kingdom, Germany, France and Netherlands and performed analyses Germany, France and Netherlands and performed analyses of existing situation in their countries. of existing situation in their countries.

On the basis of these and literature data, all of the On the basis of these and literature data, all of the project participants formulated diagnosis and conclusions project participants formulated diagnosis and conclusions concerning development of the model CFS registry in concerning development of the model CFS registry in Eastern Europe and described standards of a model Eastern Europe and described standards of a model organisational structure of Hereditary Cancer Centres in organisational structure of Hereditary Cancer Centres in Eastern Europe.Eastern Europe.

RESULTS:RESULTS:

Country CFS type

Czech Hungary Latvia Lithuania Poland TOTAL

Breast/ ovarian cancers 140 32 2 44 963 1181

HNPCC 54 12 57 13 284 420

Other or undefined CFS 66 22 1 3 1713 1805

Total 260 66 60 60 2960 3406

PARTICULAR ACHIEVEMENTSPARTICULAR ACHIEVEMENTS

Registration of ~1300 BRCA 1 mutation Registration of ~1300 BRCA 1 mutation carrierscarriers

1,253 mln of 1,45 mln of inhabitants 1,253 mln of 1,45 mln of inhabitants in West – Pomerania, Poland screenedin West – Pomerania, Poland screenedfor CFSfor CFS

TWÓJ STYL

RESULTS:RESULTS:Ad 3. Collaborative studies: A. Ongoing:Ad 3. Collaborative studies: A. Ongoing:

1.1. Clinical characteristics of families with FH gene constitutional mutations – Cybulski C., Clinical characteristics of families with FH gene constitutional mutations – Cybulski C., Mecklin J.P., Lubinski J.Mecklin J.P., Lubinski J.

2.2. Classification of hereditary cancers based on changes at protein level – Classification of hereditary cancers based on changes at protein level – Europroteome – Berlin – Lubinski J.Europroteome – Berlin – Lubinski J.

3.3. Modifying genes in patients with BRCA 1 constitutional mutations – Hamman U., Modifying genes in patients with BRCA 1 constitutional mutations – Hamman U., Goldgar D., Scott R.J., Gronwald J., Lubinski J.Goldgar D., Scott R.J., Gronwald J., Lubinski J.

4.4. Nature and frequency of MSH 6 gene mutations in Latvia – Irmejs A., Gardovskis J., Nature and frequency of MSH 6 gene mutations in Latvia – Irmejs A., Gardovskis J., Kurzawski G., Suchy J., Lubinski J.Kurzawski G., Suchy J., Lubinski J.

5.5. Family ascertainment and sample collection for identification of additional breast Family ascertainment and sample collection for identification of additional breast cancer susceptibility genes in the BRCAX study – Lubinski J., Goldgar D.cancer susceptibility genes in the BRCAX study – Lubinski J., Goldgar D.

6.6. Average risk of breast and ovarian cancer associated with mutations in BRCA1 and Average risk of breast and ovarian cancer associated with mutations in BRCA1 and BRCA2 detected in case series unselected for family history - Pharoah P., Ponder B., BRCA2 detected in case series unselected for family history - Pharoah P., Ponder B., Narod S., Gronwald J., Lubinski J.Narod S., Gronwald J., Lubinski J.

RESULTS:RESULTS:Ad 3. Collaborative studies: A. Ongoing:Ad 3. Collaborative studies: A. Ongoing:

7.7. Nuclear pedigree criteria of suspected HNPCC – Kladny J., Moeslein G., Lubinski J.Nuclear pedigree criteria of suspected HNPCC – Kladny J., Moeslein G., Lubinski J.

8.8. Founder mutations in the BRCA 1 gene in west Belarusian breast-ovarian cancer Founder mutations in the BRCA 1 gene in west Belarusian breast-ovarian cancer families – Oszurek O., Lubinski J.families – Oszurek O., Lubinski J.

9.9. Germline MSH 2 and MLH 1 mutational spectrum in HNPCC families from Poland and Germline MSH 2 and MLH 1 mutational spectrum in HNPCC families from Poland and Baltic states – Kurzawski G., Elsakov P., Gardovskis J., Irmejs A., Moeslein G., Baltic states – Kurzawski G., Elsakov P., Gardovskis J., Irmejs A., Moeslein G., Lubinski J.Lubinski J.

10.10. Concerted Action Polyp Prevention 2. A randomised controlled trial of colorectal Concerted Action Polyp Prevention 2. A randomised controlled trial of colorectal polyp and cancer prevention using aspirin in carriers of HNPCC – Lubinski J., Elsakov polyp and cancer prevention using aspirin in carriers of HNPCC – Lubinski J., Elsakov P., Burn J.P., Burn J.

11.11. Stem Cell Therapeutics – Excellence Centre - Dembinska-Kiec A., Lubinski J.Stem Cell Therapeutics – Excellence Centre - Dembinska-Kiec A., Lubinski J.

12.12. Centre of Excellence in Molecular Bio-Medicine – Witt M., Lubinski J.Centre of Excellence in Molecular Bio-Medicine – Witt M., Lubinski J.

13.13. Excellence Centre for Hereditary Cancers (Network of Excellence) – Lubinski J., Excellence Centre for Hereditary Cancers (Network of Excellence) – Lubinski J., Elsakov P., Foretova L., Gardovskis J., Haites N., Ponder B., Moeslein G., Neumann Elsakov P., Foretova L., Gardovskis J., Haites N., Ponder B., Moeslein G., Neumann H., Sobol H., Mecklin J.-P., Vasen H., Weber W.H., Sobol H., Mecklin J.-P., Vasen H., Weber W.

RESULTS:RESULTS:Ad 3. Collaborative studies: B. Proposed:Ad 3. Collaborative studies: B. Proposed:1.1. Letters of Expression of Interest for 6th Framework Programme Letters of Expression of Interest for 6th Framework Programme

(European Commission):(European Commission):-- Identification of Men with a genetic predisposition to prostate cancer and their treatment – Identification of Men with a genetic predisposition to prostate cancer and their treatment –

Eeles R.Eeles R.

-- Assessment of the therapeutic response in breast cancer - Sobol H.Assessment of the therapeutic response in breast cancer - Sobol H.

-- Clinical management of familial breast cancer (Network of Excellence) – Eccles D. Clinical management of familial breast cancer (Network of Excellence) – Eccles D.

-- Prevention of hereditary endometrial cancer – Vasen H.Prevention of hereditary endometrial cancer – Vasen H.

-- Colorectal cancer genetics: insight into cause and prevention (Network of Excellence) - Colorectal cancer genetics: insight into cause and prevention (Network of Excellence) - Burn J.Burn J.

-- Public health systems in combating hereditary cancers (Network of Excellence) – Lubinski Public health systems in combating hereditary cancers (Network of Excellence) – Lubinski J.J.

RESULTS:RESULTS:

Ad 3. Collaborative studies: B. Proposed:Ad 3. Collaborative studies: B. Proposed:2.2. Modifying genes in patients with mutations within HNPCC genes – Modifying genes in patients with mutations within HNPCC genes –

Scott R.J., Irmejs A., Kurzawski G., Marlicz K., Lubinski J.Scott R.J., Irmejs A., Kurzawski G., Marlicz K., Lubinski J.3.3. Incidence of BRCA 2 constitutional mutations in families with Incidence of BRCA 2 constitutional mutations in families with

aggregation of stomach and ovarian cancers – Jakubowska A., aggregation of stomach and ovarian cancers – Jakubowska A., Starzynska T., Lubinski J., Caldas C.Starzynska T., Lubinski J., Caldas C.

4.4. Clinical characteristics of familial pancreatic cancers – Nej K., Clinical characteristics of familial pancreatic cancers – Nej K., Starzynska T., Marlicz K., Lubinski J., Moeslein G.Starzynska T., Marlicz K., Lubinski J., Moeslein G.

WELCOME TO DEVELOP WELCOME TO DEVELOP COLLABORATIVE STUDIES COLLABORATIVE STUDIES

WITH PARTICIPATION WITH PARTICIPATION OF EAST EUROPEAN OF EAST EUROPEAN

REGISTRIESREGISTRIES !

EUROPEAN REGISTRYEUROPEAN REGISTRY

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