Inherited Colorectal Cancer

One of the risk factors for colorectal cancer is a family history of the disease. Colorectal cancer is called "hereditary" or "inherited" when several generations of a family have colorectal cancer. Several gene mutations, or abnormalities, that cause colorectal cancer, and allow it to be transmitted to family members, have been found. A gene is a block of DNA that holds the genetic code, or instructions, for producing proteins vital to our bodily functions.

The two most common inherited colorectal cancer syndromes are hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). They can affect men and women, and the children of people who carry these genes have a 50% chance of inheriting the disease-causing gene.

These two inherited cancer syndromes account for less than 5% of all colorectal cancers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch syndrome

Nonpolyposis colorectal cancer, HNPCC, is the most common form of hereditary colon cancer, accounting for about 3% of all colorectal cancer diagnoses each year. People with HNPCC often have at least three family members and two generations with colorectal cancer, and cancer develops before age 50. Although not everyone who inherits the HNPCC gene will develop colorectal cancer, the risk is very high -- about 80%. People with HNPCC also have a higher risk of developing other Lynch syndrome-related cancers, such as kidney, ovarian, uterine, renal, pelvis, small intestine, and stomach cancer.

Health care providers can evaluate the pattern of colorectal cancer in relatives in order to determine if the family has HNPCC. Families considered to be "HNPCC families" must display certain criteria indicating a pattern of colon cancer throughout generations. These are referred to as the Amsterdam Criteria, and include:

  • At least 3 members with a Lynch syndrome-related cancer
  • At least 2 successive generations with this type of cancer
  • Two family members with the disease are first-degree relatives (i.e. parents, brothers, sisters or children) of another family member with a Lynch syndrome cancer
  • At least 1 member affected at or before age 50
  • The familial adenomatous polyposis syndrome (FAP) is excluded from the family member's diagnosis

If you feel this applies to you, consult your doctor. Colonoscopies are recommended in family members who are 10 years younger than the youngest family member who was diagnosed with cancer. Screening for other Lynch syndrome-related cancers should also be performed. For people with a diagnosis of Lynch syndrome, screening usually starts between ages 20 and 25. 

 

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Familial Adenomatous Polyposis (FAP) Syndrome

Familial adenomatous polyposis (FAP) is a rare condition characterized by the presence of more than hundreds or even thousands of benign polyps, or growths in the large intestine and upper respiratory tract. It is thought to be present in about 1% of all people diagnosed with colorectal cancer each year. The polyps occur early in life, with 95% of people with FAP developing polyps by age 35, and are often detected in patients in their teens, with 50% developing polyps by age 15. If the colon is not surgically removed, there is almost a 100% chance that some of the polyps will develop into cancer, usually by age 40. Thyroid cancer is associated with FAP.

While most cases of FAP are inherited, nearly a third of the cases are the result of a spontaneous (newly-occurring) gene mutation, or abnormality. For those who develop a new gene mutation, it is possible to pass the FAP gene onto their children.

What Is the FAP Gene?

Genes are tiny segments of DNA that control how cells function, such as telling them when to divide and grow. One copy of each gene comes from your mother; the other comes from your father.

In 1991, researchers made a significant breakthrough in the diagnosis of FAP. They identified the gene -- called APC -- that is responsible for the condition. This gene mutation can be detected in 82% of patients with FAP. The exact lifetime risk of developing colon cancer in people who have inherited this gene abnormality is about 100%. Families in which this gene mutation occurs may or may not have one or more family members with colorectal cancer or polyps.

What Is the Difference Between FAP and HNPCC?

There are two main differences between FAP and HNPCC, and they include:

  1. Number of genes mutated. In FAP, there is only one gene, the APC gene, which is abnormal. In HNPCC, there are several gene, mutations which may be responsible for the development of the condition.
  2. Presence of polyps, or growths that can become cancer. FAP is characterized by the presence of more than 100 benign polyps. In HNPCC, affected people have fewer polyps, but these polyps can become cancerous more quickly than normal.

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Other Forms of Inherited Polyposis Syndromes

There are other, very rare forms of inherited polyposis syndromes that are associated with an increased risk of colorectal cancer. These include:

  • Juvenile polyposis (JP). Patients may have anywhere from five to 500 polyps, or growths, mostly in the colon and rectum, which usually begins before the age of 10. The stomach and small intestine are less commonly affected. These patients are also at increased risk of bowel cancer.
  • Peutz-Jehgers syndrome (PJS). Patients with PJS typically develop dozens to thousands of benign polyps, or growths, in the stomach and intestines, primarily in the small intestine. The growths can become malignant or can cause obstruction of the bowel.

Ashkenazi Jews and Colorectal Cancer

Jewish people who are Ashkenazi, or of Eastern European descent, are at increased risk for colorectal cancer. This is thought to be due to a variant of the APC gene that is found in 6% of this population. Ashkenazi Jews make up the majority of the Jewish population in the U.S.

If you suspect that you are at risk for an inherited form of colorectal cancer, talk to your doctor. There may be a genetic test that can be performed to confirm your suspicions.

WebMD Medical Reference Reviewed by Minesh Khatri, MD on October 20, 2016

Sources

SOURCES: 

Cleveland Clinic.

The American Journal of Pathology: "Familial Adenomatous Polyposis-Associated Thyroid Cancer."

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