Inherited Syndromes Link Cancers
by Elizabeth Whittington
Cure magazine, Summer Issue 2006
IN ADDITION to treatment-related risks, some survivors discover
they have a genetic syndrome that may lead to a second cancer.
Scientists are finding that It may not be where cancer strikes
that's Important, but what's causing It in the first place.
THE MOST well-known genetic mutations. BRCA1 and BRCA2, can
signify an increased risk of developing not only breast cancer
in men and women, but also ovarian cancer. Coupled with a
55 to 85 percent lifetime risk for breast cancer, individuals
with the BRCA1 mutation have a 40 to 60 percent lifetime risk
for developing a second breast cancer.
Li-Fraumeni syndrome, rare genetic disorder often caused
by a mutated p53 gene, can increase the risk for breast cancer,
sarcoma, leukemia, brain tumors and other cancers. Studies
have shown that people with the inherited mutation have at
least an 85 percent chance of developing cancer during their
lifetime. A study of 200 people with inherited Li-Fraumeni
syndrome found that 15 percent developed a second cancer,
4 percent had a third cancer and 2 percent had four cancers.
Childhood cancer survivors were found to be at highest risk
for second cancers.
The inactivation of a tumor-suppressor gene called von Hippel-Lindau
(VHL) may cause upto 85 percent of all kidney cancers. A person
is born with two copies of every gene, so both VHL genes must
be inactive or mutated before tumors form.
Patients with one inherited VHL mutation have a much greater
likelihood of developing kidney cancer since it only takes
a mutation of the second VHL gene for tumors to occur. In
addition to kidney cancer, VHL is associated with tumors of
the eye, brain, spine and pancreas.
Genetic syndromes only account for 5 percent of all colorectaI
cancer cases, but hereditary nonpolyposis colorectal cancer
(HNPCC), also known as Lynch syndrome, and familial adenomatous
polyposis (FAP) dramatically increase the risk. HNPCC is caused
by a defect in DNA repair genes, four of which have been identified.
Because these genes oversee DNA cell replication, defects
can cause other types of cancers, including uterine and ovarian
cancer. FAP results from only one mutated gene, but it can
increase the risk of developing colorectal cancer to 90 percent
by age 45. Thyroid, small bowel and brain cancers have also
been noted with this mutation.
For a complete list of cancer screening recommendations,
To find a genetic counselor in your area, visit the website
of the National Society of Genetic Counselors at www.nsgc.org.