The study, that CNIO has in large part coordinated and participated in, is based on massive genotyping and subsequent analysis of the genome of thousands of individuals, which makes this the largest cancer genotyping analysis to date
The results, published today in 13 articles, allow us to identify new regions of the genome associated with an increased susceptibility to developing breast, prostate and ovarian cancer
Furthermore, the study identifies genomic variants that, despite contributing very little to cancer development, could in combination explain the appearance of the disease in many patients
These results could be key for the screening and later follow-up of those patients who have a greater risk of developing cancer
The European Collaborative Oncological Gen-Environmental Study (COGS) project, whose main goal is to decipher the complex genetic bases of breast, prostate and ovarian cancers, publishes today a total of 13 research articles in several prestigious journals, including Nature Genetics, Nature Communications, The American Journal of Human Genetics and PLOS Genetics. Using mass sequencing techniques, the study has identified up to 80 new regions of the genome associated with an increased susceptibility to developing breast, prostate and ovarian cancers.
The conclusions are drawn from the collaborative work of more than 50 groups around the world, who carried out their genotyping in four different centres and whose work was coordinated by Javier Benítez, Director of the Human Cancer Genetics Programme at the Spanish National Cancer Research Centre (CNIO).
In order to identify those genetic ‘errors’ or genetic variants that might increase the risk of suffering from cancer among the general population, the project’s researchers genotyped more than 200,000 SNPs—single–nucleotide polymorphisms or genome letter changes—selected from the genome of 100,000 breast, prostate and ovarian cancer patients, as well as from 100,000 control cases without cancer.
Thanks to the massive genotyping of these individuals, the authors of the different studies published today have identified 41 new genes or regions of the genome that may be susceptible to contributing to the development of breast cancer, 23 new ones for prostate cancer and 4 for ovarian cancer.
“Specifically, the 41 new genes identified for breast cancer increase to almost 70 the number of genes that indicate a high probability of developing this illness when mutated,” explains Benítez, adding that: “these data indicate that up to 5% of the general population may have a high risk of suffering from this illness at some point in their lives”.
Amongst all of the genes identified, there are some that could help cancerous cells to spread throughout the body, others would favour the uncontrolled growth of cells and still others would help by removing the brakes that stop cells from growing.
The authors of the study have also identified TERT as the gene susceptible to breast and ovarian cancer. This finding can add up to the recent study published in Nature Genetics, led by researchers Carlos López-Otín, from the University Institute of Oncology at the University of Oviedo, Elias Campo, from the Hospital Clínic /University of Barcelona, and Maria A. Blasco, the Director of CNIO, which relates the role of telomeres and their protective function of the genetic material with the development of chronic lymphocytic leukaemia.
GENETIC HETEROGENEITY AS A CAUSE OF CANCER
According to researchers, a big surprise to come out of the study is the identification of thousands of additional genes than those described to date that, to a lesser extent, make someone more susceptible to cancer.
“In the case of breast cancer, we have discovered up to 1,000 genes that increase the risk of suffering the illness only very slightly, but when accumulated, they could explain its appearance in some patients,” explains Benítez.
These results show the enormous complexity of cancer. One example would be hereditary breast cancer, which correlates in most cases with mutations in the BRCA1 and BRCA2 genes. These tumours, however, could be explained by the accumulation of multiple mutations in genes that when appearing alone slightly increase the risk of developing cancer. “These genes would explain why many families have these types of hereditary cancers without the presence of mutations in the BRCA genes,” clarifies Benítez.
Benítez concludes: “Every tumour is born with its own distinct genetic history, so if we identify those individuals whose genetic characteristics confer them a greater probability of developing cancer, we will be able to provide them with more adequate follow-up and thus reduce the appearance of the disease or diagnose it in its initial phases.”
The collaborative effort of thousands of national and international scientists has opened new perspectives for cancer research, offering new clues to the understanding of the molecular pathways in cancer cells. These studies could also expand the possibilities in the search for new therapeutic treatments against cancer.
The CNIO, in addition to coordinating the genotyping of tumours, has also taken part in the genotyping of breast cancer studies —via the National Genotyping Centre-Instituto de Salud Carlos III (CeGen-ISCIII), in collaboration with Anna González-Neira, Head of the Human Genotyping- CEGEN Core Unit – as well as in the corresponding data analysis with the help of Ana Osorio from the Human Genetics Group and Roger Milne from the Genetic and Molecular Epidemiology Group. This work has been made possible thanks to the collaboration of the Monte Naranco hospital in Oviedo and the La Paz hospital in Madrid.
The main aims of the European COGS project are directed towards the study of the genetic and environmental factors that predispose people to the appearance of breast, prostate and ovarian cancers, the most common forms of cancer in developing countries, and towards how society might benefit from such results.
The European COGS project is the result of the collaboration between four international consortiums: BCAC, whose aim is to study breast cancer; PRACTICAL, which researches genetic alterations associated with prostate cancer; OCAC, whose aim is to study ovarian cancer, and CIMBA, which studies BRCA1 and BRCA2 modifications.
The results generated by COGS help to understand the biological processes that are involved in carcinogenesis and might also help the development of new therapeutic tools as well as predictive risk tests for the disease.
The project is member of a local communication network called CommHERE, an initiative funded by the European Commission. The goal of CommHERE is to disseminate among the society the health research results developed under the funding of the 7th Framework Programme of the EC.
Referencia del artículo destacado:
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, Schmidt MK, Chang-Claude J, Bojesen SE, Bolla MK, Wang Q, Dicks E, Lee A, Turnbull C, Rahman N; Breast and Ovarian Cancer Susceptibility Collaboration, Fletcher O, Peto J, Gibson L, Dos Santos Silva I, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Czene K, Irwanto A, Liu J, Waisfisz Q, Meijers-Heijboer H, Adank M; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), van der Luijt RB, Hein R, Dahmen N, Beckman L, Meindl A, Schmutzler RK, Müller-Myhsok B, Lichtner P,Hopper JL, Southey MC, Makalic E, Schmidt DF, Uitterlinden AG, Hofman A, Hunter DJ, Chanock SJ, Vincent D, Bacot F, Tessier DC, Canisius S, Wessels LF, Haiman CA, Shah M, Luben R, Brown J, Luccarini C, Schoof N, Humphreys K, Li J, Nordestgaard BG, Nielsen SF, Flyger H, Couch FJ, Wang X, Vachon C, Stevens KN, Lambrechts D, Moisse M, Paridaens R, Christiaens MR, Rudolph A, Nickels S, Flesch-Janys D, Johnson N, Aitken Z, Aaltonen K, Heikkinen T, Broeks A, Veer LJ, van der Schoot CE, Guénel P, Truong T, Laurent-Puig P, Menegaux F, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Zamora MP, Perez JI, Pita G, Alonso MR, Cox A, Brock IW, Cross SS, Reed MW, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Henderson BE, Schumacher F, Le Marchand L, Andrulis IL, Knight JA, Glendon G, Mulligan AM; kConFab Investigators; stralian Ovarian Cancer Study Group, Lindblom A, Margolin S, Hooning MJ, Hollestelle A, van den Ouweland AM, Jager A, Bui QM, Stone J, Dite GS, Apicella C, Tsimiklis H, Giles GG, Severi G, Baglietto L, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Brenner H, Müller H, Arndt V, Stegmaier C, Swerdlow A, Ashworth A, Orr N, Jones M, Figueroa J, Lissowska J, Brinton L, Goldberg MS, Labrèche F, Dumont M, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Brauch H, Hamann U, Brüning T; GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, Radice P, Peterlongo P, Manoukian S, Bonanni B, Devilee P, Tollenaar RA, Seynaeve C, van Asperen CJ, Jakubowska A, Lubinski J, Jaworska K, Durda K, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Bogdanova NV, Antonenkova NN, Dörk T, Kristensen VN, Anton-Culver H, Slager S, Toland AE, Edge S, Fostira F, Kang D, Yoo KY, Noh DY, Matsuo K, Ito H, Iwata H, Sueta A, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Shu XO, Lu W, Gao YT, Cai H, Teo SH, Yip CH, Phuah SY, Cornes BK, Hartman M, Miao H, Lim WY, Sng JH, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Shen CY, Hsiung CN, Wu PE, Ding SL, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Blot WJ, Signorello LB, Cai Q, Zheng W, Deming-Halverson S, Shrubsole M, Long J, Simard J, Garcia-Closas M, Pharoah PD, Chenevix-Trench G, Dunning AM, Benitez J, Easton DF. Nature Genetics (2013). doi: 10.1038/ng.2563