Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS


CCPRB Berichtzusammenfassung

Project ID: 503465
Gefördert unter: FP6-LIFESCIHEALTH
Land: Sweden

Final Report Summary - CCPRB (Cancer Control using Populationbased Registries and Biobanks)

The project maintained some of Europe's largest biobanks and most well-controlled registries in regular networking meetings to share competences and resources. This promoted design and launching of over 200 joint international biobank studies and resulted in an overall quality improvement of such studies.

The biobank databases were linked with population registries for updating on vital status and estimation of population representativeness of data as well as with nationwide cancer registries to generate cancer incidences and tables with total number of prospectively occurring cancer cases in all participating biobanks. This provided objective data on usefulness of the different biobanks and formed the basis for planning of further joint work.

A statistical analysis centre provided a service with standardised and robust methods for study design, selection of random eligible controls, generation of study files and pick-up lists, third party code-keeping and statistical analysis of joint biobank-based studies. The analysis centre also advanced the methodology of biobank-based studies by exploring the statistical issues surrounding re-use of controls in case-cohort studies and estimation of absolute risk from nested case-control studies.

The quality assurance system, Good Biobanking Practise, has resulted in traceable quality of samples and greatly improved efficiency in management and coordination. As an example, the statistics in terms of numbers of samples stored as well as number of samples delivered greatly increased, resulting in a scientific output from CCPRB, with about 200 publications at the time of writing. Joint quality control methods were agreed upon and the CCPRB standard procedures for evaluating quality of DNA were prominently published.

The speed of development of quality standards and dissemination throughout the network was increased by the use of a joint Internet-based quality manual system. The proposed quality standards for building of population-based biobanks of liquid-based cervical cytology specimens were expected to greatly impact the building of a uniquely large infrastructure for molecular epidemiology in Europe.

As use of biobanks is critically dependent on accurate linkages with comprehensive and high-quality health data registries, cancer registration and the use of registry data is also being quality assured. Quality assurance systems for completeness and accuracy of cancer registration as well as for linkage of registry data, pathology data and biobank databases were established.

For streamlining the management of the biobank information, a joint CCPRB biobank laboratory information management system was purchased. The system was installed at the coordinator's institute, but as it is Internet-based, all the partners can use it in the same manner as if there had been separate installations for each partner. As the same configuration of the system is used, the databases are harmonised and overview and joint work is facilitated.

A comprehensive linkage of the Swedish cancer registry and multigeneration registry enabled a systematic assessment of familial risks for many cancers, including colorectal, prostate, cervical, bone and testicular cancers and non-Hodgkin lymphoma and childhood leukaemia. Cancer risks were also assessed in twins and in offspring of lung cancer parents with some mechanistic inferences. These data formed the basis for an epidemiologically focused and thus maximally efficient investigation of the genes determining genetic susceptibility of cancer.

These studies also discovered that there exists genetic determinants of survival in cancer, that are distinct from the genetic determinants that convey risk for cancer per se. The CCPRB network provided the required population-based samples with long-term follow-up that enabled a genome-wide scan to identify the specific genetic determinants of breast cancer survival.

A number of very large-scale association studies within the participating biobanks with familial or sporadic breast cancer and colon cancer were performed, evaluating candidate SNPs in signalling pathways, including the GH-IGF, metastasis, cell signalling and apoptosis pathways. Several whole-genome scans were also performed by CCPRB partners and resulted in identification of new cancer-causing genes in colorectal cancer.

A comprehensive linkage of maternity cohort biobanks with cancer registries identified a uniquely large study base (more than 1 000 cases and 2 000 000 controls) for studies of intrauterine exposures and risk of childhood leukaemia. A series of studies evaluating candidate exposures was completed. High-throughput technology platforms were streamlined to allow for ongoing screening for both antibodies as well as genomes of microbial agents.

Another major finding was the discovery of frequent recombination between TT virus genomes in maternal sera from childhood leukaemia index pregnancies. These recombinations result in fusion proteins being expressed, with the coding information for these proteins being derived from different viruses.

The work of an ethical advisory board greatly improved the ethical awareness of the entire network and a series of analyses of the ethical issues of practical relevance for the scientific work (e.g. on the implications of broad informed consent and the importance of the wording of the original informed consent when considering new biobank-based studies) was prominently published.

The first formal Graduate School in Biobank-based Epidemiology was established as a part of the European Programme in Public Health and Epidemiology, with the first students starting in autumn 2005 and completing their doctoral degrees in 2008. The second class of students was admitted to the Graduate School in Biobank-based Epidemiology in autumn of 2007. A series of open, internationally announced, CCPRB courses were given, including Introduction to Molecular Epidemiology, Good Laboratory Practice in Biobanking, Science of Registry Linkages, Biobanking Ethics, Longitudinal Studies, Meta-analysis, Genetic Epidemiology and a CCPRB Biobank Conference. Finally, the first practical hands-on textbook on best practise procedures in biobanking was written and was expected to be published in 2009 as a part of the Methods in Molecular Biology book series.

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