| What
is hereditary colon cancer?
Approximately 5% of all colon (large bowel) cancers are directly caused by
inherited genetic abnormalities. These hereditary colon cancers often
feature colonic polyps or growths that eventually become cancerous. There
are several kinds, including familial adenomatous polyposis (FAP) and a
variant called Gardner's syndrome. Another type, hereditary non-polyposis
colon cancer (HNPCC), features few if any polyps. Relatively rare hereditary
conditions such as Peutz-Jeghers syndrome and juvenile polyposis are not
cancer or precancerous conditions but confer on the patient a greater than
normal risk of developing colon cancer. Many families with higher than
normal rates of colon cancer have one or more of these conditions. While
non-hereditary ("sporadic") colon cancer rarely occurs before age 40,
hereditary colon cancers often occur in younger people.
Experts in hereditary colon cancers
strongly recommend that people with unusually high rates of colon cancers in
their families be surveyed regularly for cancerous growths, even if they
have no symptoms. Colonoscopy is the most effective and most
widely used method of surveillance for hereditary colon cancers. In
colonoscopy, a narrow flexible tube is inserted into the colon through the
rectum. At the end of the tube is a tiny light and video camera which allows
the physician to see the inside of the colon.
Colonic polyps, or adenomas, are relatively easy to diagnose by colonoscopy.
FAP and Gardner's syndrome are characterized by hundreds, even thousands, of
polyps. If the disease is caught in the precancerous stage, cancer can be
prevented by removing the colon surgically. If the disease has progressed to
the cancerous stages, surgery may or may not be an effective treatment. In
families known to carry a gene for one of these diseases, surveillance for
polyps should begin at age 10 to 12.
Although HNPCC usually does not feature the highly
conspicuous polyps, it too is best detected with colonoscopy. One type,
Lynch syndrome I, begins at a young age, is more likely to be in the
proximal (upper, or right) colon, and is often accompanied by other colon
tumors. Lynch syndrome II has all of these features and is also often
accompanied by cancers outside the colon, especially in the endometrium (the
lining of the uterus) and the ovaries. HNPCC may also be associated with
cancers of the stomach, small bowel, pancreas, urinary tract, or larynx in
some families. In families known to be affected by HNPCC, regular
surveillance with colonoscopy should begin at about age 25.
Many clinics, hospitals, and cancer
centers that treat people with hereditary colon cancer maintain registries.
A registry is a list of families known to be affected by a
particular genetic disease. These lists help identify all the family members
who might carry the disease and should be surveyed. Registries and regular
surveillance help save lives by prevention and early detection of hereditary
colon cancers. |
Unlike patients who are carriers of well-recognized
genetic mutations like BRCA1 or BRCA2, these women do not have any evidence
of genetic alterations that would increase the risk of breast cancer. The
increased breast cancer risk in this group of women may be related to a
group of genes rather than a single gene mutation. These genetic alterations
as a group may have increased predisposition to development of breast
cancer. It is also difficult to separate environmental factors in these
patients. The role of environmental factors is difficult to quantify in this
situation and how much of this increased risk is caused by common
environmental factors is difficult to judge. If a woman, say Miss A has a
first degree relative (mother, daughter, or sister) with diagnosis of breast
cancer, the risk of Miss A developing breast cancer is 1.7 times higher
(called relative risk) compared to the general population. If that
first-degree relative of Miss A had developed breast cancer prior to the
menopause, the relative risk for Miss A would be 3 fold. On the other hand
if that relative had breast cancer after menopause, the relative risk for
Miss A would be 1.5 fold. If that relative had developed bilateral breast
cancer then the relative risk for Miss A would be 5 fold higher. Again if
that relative who developed bilateral breast cancer had developed the breast
cancer prior to menopause, the relative risk for Miss A would be 9 fold
higher. You can see here complex factors playing roles to increase the risk
of breast cancer.
A
similar situation is present in colon cancer as well, there are specific
identifiable genetic mutations that gives rise to very high risks of
developing colon cancer. Mutation in the APC gene is a noted
example. If a person carries this mutation that person has close to 100%
risk of developing colon cancer in the late adulthood. This gene is
transmitted in an autosomal dominant model, which means that any offspring
of the carrier has a 50% risk of inheriting this mutation and subsequent
increased risk of colon cancer. As with breast cancer most cases of colon
cancer are not related genes that could be tested. Colon cancer diagnosis in
a person would increase the risk of colon cancer development in his close
relatives. Again as mentioned above this is not the result of a single
genetic abnormality that is inherited, but is really due to interaction of a
group of genes and various environmental factors common to the family like
eating habits and food preferences.
Most of the familial cancers are multi-factorial and most of the time there
are no demonstrable genetic markers or patterns. A small percentage of the
cancers can be truly genetic with identifiable genetic markers. The pattern
of familial clustering is more in some cancer like breast cancer, colon
cancer, and ovarian caner but less in many other types of cancers like lung
cancer, prostate cancer, and esophageal cancer.
The following is a list of identified familial genetic syndromes associated
with a single genetic abnormality. Please not that this is not a
comprehensive list of all known disorders.
Autosomal dominant disorders
| BRCA1: Breast cancer |
BRCA2: Breast cancer |
| APC: Colon cancer |
HNPCC: Colon cancer |
| CDKN2: Melanoma |
|
| Basal cell nevus syndrome |
Neurofibromatosis type 2 |
| Carney syndrome |
Osteochondromatosis, multiple |
| Chordoma, familial |
Paraganglioma, familial |
| Cowden syndrome |
Peutz-Jeghers syndrome |
| Esophageal cancer with tylosis |
Prostate cancer |
| Gastric cancer, familial |
Renal cancer, familial |
| Li-Fraumeni syndrome |
Retinoblastoma |
| Multiple endocrine neoplasia type 1 |
Tuberous sclerosis |
| Multiple endocrine neoplasia type 2 |
von Hippel-Lindau disease |
| Neurofibromatosis type 1 |
Wilms' tumor |
Autosomal recessive disorders
| Ataxia-telangiectasia |
Rothmund-Thomson syndrome |
| Bloom syndrome |
Xeroderma pigmentosa |
| Werner's syndrome |
Fanconi's anemia |
|
