How Do I know If I Am at
Risk of Developing an
If, in your family there is/are:
1. Many cases of an uncommon or rare type of cancer
(like kidney cancer).
2. Members diagnosed with cancers at younger ages than
usual (like colon cancer in a 20 year old).
3. One or more members that have more than one type of
cancer (like a female relative with both breast and ovarian
4. One or more members with cancers in both of a pair
of organs simultaneously (both eyes, both kidneys,
5. More than one childhood cancer in siblings (like sarcoma
in both a brother and a sister).
6. A close relative, like a parent or sibling, with cancer.
7. A history of a particular cancer among relatives on the
same side of the family.
Inheritable Causes of Cancer
Inherited Risk: It’s in Your Genes
We now know that most, if not all, tumors arise from several
genetic mutations that have accumulated in one cell of the body
during the patient’s lifetime. Unfortunately, in some families,
several members can inherit a genetic mutation linked to cancer
and have an increased risk for certain forms of the disease from
birth. The NCI estimates that about 5% to 10% of all new cases of
cancer in the U.S. each year, which is approximately 50,000 cases,
are associated with an inherited mutation (( 48); see Table 4, p. 38).
Retinoblastoma is one of the first cancers documented to be
caused by an inherited, cancer-predisposing genetic mutation in
some individuals ( 49). Retinoblastoma is a cancer of the eye that
usually develops in early childhood, typically before the age of five.
Although it is a rare cancer, diagnosed in just 250 to 350 children in
the U.S. per year, analysis of retinoblastoma in the 1970s and
1980s revealed several of the tenets that underpin our current
understanding of all cancers. For example, research demonstrated
for the first time that mutations in a tumor suppressor gene, in this
case the RB1 gene, could initiate tumor formation. The important
American Association for Cancer Research
role that these findings played in advancing cancer research
highlights the need to study all cancers, even those that affect very
Cancers linked with inherited mutations in the tumor suppressor
genes BRCA1 and BRCA2 are much more prevalent than those
associated with RB1 mutations. They constitute about 5% to 10% of
breast cancer cases, such as Melanie A. Nix’s, and 10% to 15% of
ovarian cancer cases ( 50). A woman who has inherited a cancer-susceptibility mutation in one or both of these genes is about five
times more likely to develop breast cancer and more than 10 times
more likely to develop ovarian cancer compared with a woman who
does not have such a mutation ( 51). Men who inherit these mutations
are also at increased risk for developing breast cancer as well as
pancreatic cancer and an aggressive form of prostate cancer.
Currently there is no way to correct inherited cancer-susceptibility
mutations. However, the knowledge that an individual is in a high-risk category can encourage him/her to modify their behaviors to
reduce risk from other factors, such as the use of tobacco and
alcohol consumption; intensify participation in screening or early
detection programs; or under certain circumstances, consider the
options of taking a preventive medicine or having precautionary
surgery to remove organs that are at greatest risk for cancer, as
Melanie A. Nix did. At least some of these options are available to
all patients who know they have a cancer-associated mutation, but
additional research is needed to define the most comprehensive
strategies for cancer risk reduction in different patient populations.
Despite clear advances in our understanding of inherited cancer
risk, much remains to be learned. For example, although we know
that a family history of cancer is a sign that a person may have
inherited a cause of cancer (see Sidebar on How Do I Know If I
Am at Risk for Developing an Inherited Cancer?), in most cases
we do not know what the inherited genetic mutation is.
Furthermore, we need to understand the genetic underpinnings of
the inherited risk, which is one of many components contributing to
that having an affected first-degree
relative (parent, sibling or child) roughly
doubles an individual’s risk of
developing colorectal cancer?