Inherited forms of common cancers

Inherited forms of the common cancers, notably breast, ovary
and bowel, constitute a small proportion of all cases, but their
identification is important because of the high risk of
malignancy associated with inherited mutations in cancer
predisposing genes. Identification of such families can be
difficult, as tumours often vary in the site of origin, and the risk
and type of malignancy may vary with sex. For example, in
HNPCC, females have a higher risk of uterine cancer than
bowel cancer. In breast or breast–ovary cancer families, most
males carrying the predisposing mutations will manifest no
signs of doing so, but their daughters will be at 50% risk of
inheriting a mutation, associated with an 80% risk of
developing breast cancer. With the exception of familial
adenomatosis polyposis (FAP, see below), where the sheer
number of polyps or systemic manifestations may lead to the
correct diagnosis, pathological examination of most common
tumours does not usually help in determining whether or not a
particular malignancy is due to an inherited gene mutation,
since morphological changes are seldom specific or invariable.
Determining the probability that any particular malignancy is
inherited requires an accurate analysis of a three-generation
family tree. Factors of importance are the number of people
with a malignancy on both maternal and paternal sides of the
family, the types of cancer that have occurred, the relationship
of affected people to each other, the age at which the cancer
occurred, and whether or not a family member has developed
two or more cancers. A positive family history becomes more
significant in ethnic groups where a particular cancer is rare. In
other ethnic groups there may be a particularly high
population incidence of particular mutations, such as the
BRCA1 and BRCA2 mutations occurring in people of Jewish
Ashkenazi origin.