The recent publicity surrounding Angelina Jolie’s decision to talk about her family history, her decision to have genetic testing and the prophylactic surgery she has had, has raised awareness of the potential benefits of analysing the breast cancer genes to give more accurate information on an individual’s personal risk of developing breast and ovarian cancer. However several key clinical issues require clarification.

Traditionally genetic testing has been offered to families in which there is a strong family history with several closely related individuals in a particular family having developed cancer. We know that different cancer types can occur in families; a well known pattern is breast cancer and ovarian cancer occurring in the same family; another well recognised pattern is bowel cancer and womb cancer.

Testing for the breast and ovarian cancer genes (BRCA1 and BRCA2) follows a two stage clinical process. In the first stage we take a blood sample from a lady in the family who has developed either breast or ovarian cancer, and then analyse the complete sequence of her BRCA1 and BRCA 2 genes. These genes are made up of the letters C, G, A and T arranged in a long and unique sequence. The BRCA1 gene is made up of 100,000 letters arranged in sequence, and a faulty gene is caused by a very subtle change in the sequence, often consisting of a single spelling mistake, which can be found anywhere in the entire sequence. Only if we manage to identify a spelling mistake in the blood sample of the individual with breast or ovarian cancer can we then move on to the second stage of the process, and determine whether a well relative in that same family has inherited the same spelling mistake. If she has the same mistake then she has inherited the faulty copy of the gene and is at significantly increased risk of developing breast or ovarian cancer at some time in her life. If she does not have that specific spelling mistake then she has inherited the good copy of the gene, and has the same risk of developing breast or ovarian cancer as anyone else of her age in the general population. We follow a similar two stage process in families with a strong history of bowel cancer, but look at the sequence of a different set of genes; those we know are involved in inherited bowel cancer. However we often see families with a strong history of breast and ovarian cancer, in which we cannot identify a fault in either BRCA1 or BRCA2.

Recently a new test has been introduced into the UK private sector by Myriad Genetics Inc, which examines the sequence of 25 genes from a single blood sample, thus allowing a much wider range of genes to be examined in any family. The early results (from 40,000 samples tested) suggest that we are able to identify faulty genes in many more families, allowing us to give a much more accurate estimate of an individual’s risk of developing different types of cancer, and therefore encouraging more targeted screening strategies. It is now even more important than before to ensure that everyone offered genetic testing is given accurate and understandable information about their own individual risk, and the clinical implications of the genetic test results for them.

Dr James Mackay is a Consultant Genetic Oncologist in the London Breast Clinic