New genetic variants may increase susceptibility to breast, prostate and ovarian cancers

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  a  total  of  12  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 (http://www.cnio.es/es/news/docs/maria-­‐ blasco-­‐nature-­‐genetics-­‐17mar13-­‐es.pdf).

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.

Source: European Collaborative Oncological Gen-­‐Environmental Study