Genetics of breast and ovarian cancer

Studies of familial breast and ovarian cancer have traditionally been directed towards a single type of cancer, but recent evidence leads us to consider these two types of cancer together. The original evidence for a common hereditary basis for breast and ovarian cancer comes from the observation of large families with several cases of both types. The number of cancers in these families was too great to be explained by chance and none of the known environmental risk factors are sufficient to account for the clustering. Statistical analysis performed on a number of breast-ovary cancer families identified by Dr Henry Lynch and his colleagues led them to conclude that the clustering could be explained by the effect of a single dominant gene. Women with breast cancer are at increased risk of developing a second primary cancer of the ovary; and relatives of women with breast or ovarian cancer are at roughly double the risk for either tumour. The most convincing evidence, however, for a common predisposition for breast and ovarian cancer comes from genetic linkage studies. In a linkage study cancer susceptibility in a family is shown to be transmitted with a particular allele of genetic marker of known chromosomal location. A gene from chromosome region 17q12-q21, designated BRCA1, identified in 1990 by Dr Mary-Claire King and colleagues, predisposes to both cancer of the breast and the ovary.