Abstract

It has long been recognised that some very rare forms of cancer predisposition, such as retinoblastoma, are caused by inherited gene mutations [7]. It is only within the last decade or so, however, that rapid progress has been made in understanding the role that inherited mutations also play in determining a proportion of the more common cancers, including breast, colorectal and ovarian cancer [1,2,3,4,6,8,9,10]. Although there is still uncertainty about the precise contribution of inherited predisposition genes to the incidence of these cancers, the available evidence suggests that breast, colorectal and ovarian cancer have a number of common genetic features: • A small proportion of these cancers (about 5%) are caused by inherited gene mutations which, though comparatively rare, confer very high lifetime risks of developing cancer. In some cases these lifetime risks may be as high as 80%. • Cancers caused by these high-penetrance genes are likely to occur at an earlier age than sporadic cancers, and 15 – 20% of the cancers diagnosed in people under the age of 50 may be accounted for by these genetic mutations. • Carriers of known genetic mutations which confer high lifetime risks of developing breast, colorectal or ovarian cancer are also at a somewhat increased risk of developing certain other forms of cancer. • A further 10 – 20% of breast, colorectal and ovarian cancers may be caused by other inherited predisposition genes which are less penetrant but which confer some increased risk (more than 3 times the general population risk). These “medium risk”genes are only beginning to be identified.