BRCA1, BRCA2, Breast and ovarian cancer

To understand the genetics of breast cancer, we first need to explain some basic principles:

Our genetic information is contained in individual packages called chromosomes. We each have 46 chromosomes which are divided into 23 pairs: 22 pairs of autosomal chromosomes and one pair of sex chromosomes. We inherit one chromosome of each pair from our father (23) and one chromosome of each pair from our mother (23).

A chromosome consists of a single long strand of DNA containing our genetic code. A gene is a fragment of DNA, somewhere on the chromosome, that contains the code for a protein with a specific role. The information on each chromosome of the pair is the same, so we have two copies of each gene.

BRCA1 and BRCA2 are genes that code for a protein that normally protects the individual against developing cancer. Where there is an error or mutation in one or another of the genes, the risk of developing cancer is greatly increased. Abnormalities in BRCA1 and BRCA2 genes may also be inherited and the chance that an affected individual will pass on the abnormality to his / her child is 50%.

Female carriers of the BRCA1 or BRCA2 mutation have a significant risk of developing breast and ovarian cancer (Table). The risk of breast cancer is probably equal for the carriers of the BRCA1 or BRCA2 mutations, exceeding over 80%. The risk of developing ovarian cancer is significantly higher in female carriers of the BRCA1 mutation.

The cancer risk is likely elevated in male carriers of the mutations, although to a much lesser extent. Men seem to be at a particular risk of developing breast cancer if they are carrying the BRCA2 mutation.

This knowledge and the mode of transmission enable us to identify families that may be potential carriers. It includes families with a breast cancer diagnosis at a young age, a history of breast and ovarian cancer, bilateral breast cancer in one or more relatives, or male breast cancer in the family.

One can see that these are also the criteria used to identify families at risk of breast cancer.

Table: Risks associated with having a mutation in the BRCA1 or BRCA2 gene*

Female carrier  
Breast cancer 85% 86%
Contralateral breast cancer ** 60% 55%
Ovarian cancer 63% 27%
Male carrier  
Breast cancer possibly increased 7%
Cancer possibly increased possibly increased
Prostate cancer 33% 34%
Melanoma - 5%

* These risks are derived from studies of families with significant BRCA1 and BRCA2 mutations and can therefore be seen as a maximum.

** Breast cancer in the other breast of a woman with breast cancer


Patients often wonder if they may be the source of a particular mutation, but this is rarely the case. In almost all instances the mutation is derived from a parent. This explains why the mutation in a BRCA1 or BRCA2 gene can be detected in a large number of people from the same family suffering from breast or ovarian cancer. It also explains why a mutation is almost never detected in patients without a family history, even if they are diagnosed with cancer at a young age.

Mutations in the BRCA1 and BRCA2 genes can occur anywhere along the length of the gene and there are no ‘hot-spots’ or frequently recurring mutations. As a result of the large size of both genes, the molecular analysis is time consuming and intensive: it takes about 3 to 6 months per patient. The complexity of both genes also has a negative influence on the sensitivity of the analysis. The sensitivity depends on the types of mutations that occur in a given population and all forms of the mutation may not be detected using the same technique.

Although both genes can be completely analyzed, one needs to bear in mind that the result may be falsely negative: the particular abnormality of the BRCA1 or BRCA2 gene may not be identified by the technique used.