Risk Diversity

20Dec09

I have referred to different risks for the different positions of BRCA2 mutations, but I haven’t explained where I got this idea. It’s comes from a 2004 study done by Polish, Canadian, and American researchers. The study looked at cancer cases in 440 families with BRCA2 mutations. It finds further evidence of the Ovarian Cancer Cluster Region: a region in the BRCA2 gene where mutations are associated with a higher rate of ovarian cancer. This area is roughly in the middle of the gene sequence between nucleotides 3035 to 6629. If that makes no sense to the BRCA+ reader, you might want to pull out the Myriad Lab report you have. The mutation type normally starts with three or four numbers in the beginning. These numbers indicate the nucleotide where the mutation starts, its position within the gene. The rest of the mutation type indicates whether it was an insertion (ins), deletion (del), or substitution (>) and its change.

So what’s the big deal about the Ovarian Cancer Cluster Region (OCCR)? Well, 51% of families with mutations in that region have a history of ovarian cancer. But for mutations before and after this region, only 29% and 34%, respectively, of families have a history of ovarian cancer. There is a tradeoff here too. Mutations in the OCCR are found to have nearly half the risk of breast cancer compared to mutations outside of the OCCR according to an earlier study by Thomson et al.

My family has a mutation before OCCR and the risk of ovarian cancer for BRCA2 mutations was quoted by Myriad as up to 27% (based on a study from 1998!). I find it interesting, however, that the Myriad report made no mention of the OCCR. It was first discussed in 1997 by Gayther et al., so the information has been around for a while. Did Myriad take the mutation position in account when giving out stats? Anyone else want to share the info or numbers they got from Myriad? Do genetic counsellors go through this type of more detailed information?

Where I first heard of BRCA, I had no idea that the risks were so individualized. Knowing nothing of genetics, I assumed one defective gene is same as another. But apparently that is not true at all. Now I am eager to get my hands on much risk information as possible. Aren’t any decisions that I need to make inevitably going to be motivated by statistics? But are BRCA mutation carriers getting all information they need and want (without having to search university research libraries themselves)?

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