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Collaborative Oncological Gene-environment Study

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Genetics, lifestyle and environment in cancer risk

A better understanding of what factors contribute to the risk of certain types of cancer can help in developing both predictive tools and intervention strategies.

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The 'Collaborative oncological gene-environment study' (COGS) project is working to more precisely define the individual risk of disease by taking into account all possible influencing factors. Researchers have five major objectives: to identify genetic variation underlying increased risk for breast, ovarian and prostate cancer; to assess interaction between genetic loci and known or suspected environmental/lifestyle risk factors; to assess whether the link between genetic factors, environmental/lifestyle risk factors and cancer risk is stronger for certain tumour subtypes; to develop comprehensive risk models for these cancers; and to investigate the efficacy and cost-effectiveness of using these risk models in prevention strategies. Statistical analyses are being used to identify genetic loci through a multi-step procedure, with resulting genotyping results forming the basis for subsequent project activities. Initial work in this EU-funded project has focused on identifying the 200 000 single nucleotide polymorphisms (SNPs) that will be put on the Illumina iSelect chip, to be generated by one of the consortium partners. SNPs, the most common type of genetic variation found in the same biological species, offer information on how genetic make-up is linked to disease development and therapeutic responses. Datasets have been made up from existing genetic association studies (GWASs) in breast, prostate and ovarian cancer. These will be used to derive estimated genotypes for all subjects. During the first year of the project, efforts went into quantifying and organising the DNA received from partners all over the world. Actual genotyping has been scheduled to begin when the chip is delivered. Negotiations have been conducted for the purchase of an iCOGS chip for SNP selection and genotyping. The first cancer chip of its kind, this achievement allows for genotyping across all consortia and provides a means of eliminating candidate SNPs at each locus. Thanks to advances in methods of data generation, 55 loci (18 loci for breast cancer, 27 for prostate, 6 for ovarian, 4 implicated in various other cancers) have already been examined. Data mining of data released by the 1000 Genomes Project and the Hapmap project have made it possible to compare numbers of the common variants identified. In work investigating gene-environment interactions placing individuals at risk for cancer, study questionnaires have been uploaded onto the websites of project partners. These links are also provided on the COGS website. Variables for all the risk factors have been coded, with more detailed variables having been defined for more in-depth analysis in subsets to be carried out at a later stage. As work continues, consortium partners continue to lay the foundations for planned studies in order to fulfil project objectives. COGS researchers expect that as new discoveries are made and environmental/lifestyle factors are identified, the project will succeed in offering explanations for individual variations in disease risk. The results of this project will also lead to enhanced knowledge of the biological processes underlying carcinogenesis. This is important for guiding new therapeutic strategies, as well as for developing tests for risk prediction.

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