Understanding the genome to this degree of detail demands a lot of work. The weight of each risk-modulating element is small, so thousands of samples are needed for the effect to show in the data.
To do the work for the study that has been published, the researchers created a consortium called CIMBA (The Consortium of Investigators of Modifiers of BRCA1/2) in 2006, made up of research groups from around the world. CIMBA, with data from more than 40,000 carriers of BRCA1 and BRCA2 mutations, has the largest number of samples from which mutation interactions with SNPs can be studied.
Up to now, CIMBA has managed to associate more than 25 SNPs with the risk of developing breast or ovarian cancer in carriers of BRCA1/2 mutations. The study led by CNIO researchers adds at least two more to the list.
To find them, the study's authors worked in two phases: they first analysed samples from 1,787 Spanish and Italian carriers of BRCA1/2 mutations, and managed to identify 36 potentially interesting SNPs; they later investigated their importance in a further 23,463 CIMBA samples. They thus discovered 11 SNPs that indicate risk, especially so in the case of two of them. Their influence is smallthe largest risk multiplier is just 1.12which is to say 12% on the base risk.
As Osorio explains: "The weight of each of these SNPs is very small, but with the 27 already described, the risk might increase or decrease for a woman who is a carrier of mutations."
KNOWING WHERE TO LOOK
The newly discovered SNPs are in two genes known as NEIL2 and OGG1, and not by chance. The researchers went straight to the place where they found them. This way of working distinguishes this study from others that look for BRCA1/2 risk modulators by brute force: analysing and comparing everything to everything.
What advantages does searching with a compass offer? As well as
|Contact: Nuria Noriega|
Centro Nacional de Investigaciones Oncologicas (CNIO)