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Colorectal polyps and cancer develop because of a gradual build-up of changes
in the genes of cells lining the colon and rectum. A gene is a block of DNA that
holds the genetic code, or instructions, for making one particular protein.
We have two copies of each gene, one from our mother and one from our father.
Each of the two copies provides the recipe for a protein that has a unique
function in our body. For example, there are proteins that determine the color
of our eyes and the height to which we will grow.
There are many genes that control the growth, repair and death of the cells
lining the colon. Some tend to accelerate growth and some tend to slow it down.
Normal cell growth, maturation and death are therefore the result of a balance
of the effects of these growth-controlling genes and the proteins they produce.
Suppose a gene that normally accelerates cell growth is more active than
usual and produces extra proteins. Affected cells will grow faster and live
longer than their neighbors. When these affected cells divide, all daughter
cells will grow faster and live longer than normal. As more mutations happen in
this family of cells, subsequent generations grow out of control. If these
abnormal cells are in the lining of the colon or rectum, they form a polyp. If
cells in the polyp are so uncontrolled that they are able to live and reproduce
when they are apart from other cells (where they can spread to other organs),
they become a cancer.
What causes mutations to occur?
Mutations, or changes in the structure of a gene, happen for several
reasons. Chemicals in stools, or feces, usually cause mutations in the colon and
rectum. These chemicals are found in the food we eat, or are produced from these
foods during the process of digestion. Mutations are likely to occur in the
cells lining the colon and rectum because stool usually stays in the large
intestine for 24 to 36 hours, allowing time for cancer-causing chemicals
(carcinogens) to have an effect. In comparison, it only takes two to four hours
for stool to get through the small intestine, making cancer extremely rare in
this area.
This helps explain why certain foods promote colon cancer and some protect
against it. Red meat and animal fat are processed into carcinogens, while fiber
not only speeds up the passage of stool through the colon, but also is
transformed into growth-stabilizing chemicals.
Mutations that encourage cells to grow faster and live longer are most likely
to have an effect on the cells lining the colon and rectum. The cells lining the
colon and rectum are very active cells. They normally live for only six to seven
days before dying and being shed into the bowel where they are mixed into stool.
New cells are constantly being produced. If these new cells divide and grow
twice as fast and live twice as long as normal because of mutations, it is easy
to see how a visible growth will result.
Sporadic mutations
Nine out of 10 cancers of the colon and rectum develop because of sporadic
mutations in the cells lining the bowel. Sporadic mutations, which happen at
random, accumulate over time and are caused by diet and the effects of advancing
age. This is why sporadic colon and rectal cancers occur more frequently in
older people, and are more common on the left side of the colon, where the stool
tends to be stored.
Inherited mutations
Sometimes a cancer-predisposing mutation is inherited. An inherited mutation
is passed from a parent to a child. It is present in one of the germ cells (egg
or sperm) that unite to make a fetus and is reproduced in every cell in the
child's body. If a child has inherited a mutation, all cells are prone to
abnormal growth. This is why, in families where there is an inherited mutation
that causes colon or rectal cancer, other organs may also develop tumors.
A parent has two copies of each gene. If one copy is mutated there is a 50/50
chance of it being transmitted to their child.
Sometimes a cancer-causing mutation happens during conception, when the sperm
cell from a normal father and the egg from a normal mother come together. A new
family of cells is then made in which the mutation is passed from generation to
generation.
Inherited disease
When an inherited mutation causes a disease, not every person who inherits
the disease is affected in the same way. While each family member may have the
same gene, this gene may have different mutations that cause different effects.
Sometimes a mutation has no effect on a protein so there is no disease
associated with it. If the mutation produces an abnormal protein, but the
protein still works to some extent, the disease may be mild. When the mutation
produces either no protein or a protein that does not work at all, the result is
a severe form of the disease.
In addition, there may be factors in our diet or body and in other genes that
have an effect on the way a mutation produces disease. This is obvious in
families where people have the same mutation (because it is the one that is
handed down from parent to child), but they have different types of disease. In
some it develops when younger, and in others when older — and the disease may
be severe or mild.
Inherited colorectal cancer
The term "inherited" or "hereditary" colorectal cancer
is used when multiple generations of a family have colorectal cancer. Many
mutations in different genes that cause hereditary colorectal cancer have been
found and are thought to be a part of the DNA mismatch repair system leading to
the development of the disease. There also may be other genes that have not yet
been discovered.
The two most common and well-described inherited colorectal cancer syndromes
are:
Hereditary non-polyposis colorectal cancer (HNPCC) — HNPCC
patients often have at least three family members and a history of two
generations with colorectal cancer, and cancer develops before age 50. HNPCC
is thought to affect about 5 percent of all people diagnosed with colorectal
cancer each year.
Familial adenomatous polyposis (FAP) — Patients with FAP develop
hundreds of colon polyps at a young age, often have a strong family history of
colon cancer and will develop colon cancer if preventative measures are not
taken. FAP is thought to affect about 1 percent of all people diagnosed with
colorectal cancer each year.
Other rare forms of inherited colorectal cancer include:
- Juvenile Polyposis (JP)
- Peutz-Jehger's Syndrome (PJS)
What is familial colorectal cancer?
When colorectal cancer occurs in more than one family member, it may be due
to chance alone. However, it could mean that the potential risk for developing
colorectal cancer has been passed from one generation of the family to the next.
This means that relatives of a person with colorectal cancer may be more likely
to develop the disease.
Approximately 15 percent to 50 percent of colorectal cancer cases are
familial, which means that there is a tendency for colorectal cancer to develop
in the family. A single gene, a combination of genes or a combination of genetic
and environmental factors can cause familial colorectal cancer. Typically, these
families have more than one family member with a history of colorectal cancer or
pre-cancerous polyps.
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