Hereditary Colon Cancer and Polyposis

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A number of hereditary cancer syndromes are associated with an increased risk of colon cancer.

“Polyposis” refers to the presence of multiple polyps, or growths, in the gastrointestinal tract. Several types of polyps can form in the gastrointestinal tract. Adenomatous polyps (also called adenomas) are noncancerous polyps, but there is a risk that they’ll develop into cancer over time.

In addition to the hereditary cancer syndrome called Lynch syndrome, other syndromes and genetic mutations are associated with an increased risk of colon cancer.

Familial Adenomatous Polyposis (FAP) and Attenuated Familial Adenomatous Polyposis (AFAP)

FAP and AFAP are associated with having a large number of polyps. They are caused by mutations in the APC gene. People with a first-degree relative (a parent, sibling, or child) with FAP or AFAP have a 50% chance of having inherited the familial APC genetic mutation.

Anyone can have FAP or AFAP, even if it doesn’t run in their family. This happens if the APC gene gains a genetic mutation during fetal development. This APC mutation can then be passed on to their children. Each child would have a 50% chance of inheriting the mutation.

Many people with FAP develop hundreds to thousands of polyps in their colon, which is associated with a very high risk of developing colorectal cancer.

FAP can also cause conditions in other areas of the body, such as:

  • bony growths called osteomas
  • extra or missing teeth
  • a rare eye condition called congenital hypertrophy of the retinal pigment epithelium
  • noncancerous skin cysts
  • noncancerous tumors in the belly
  • polyps or cancer in other parts of the gastrointestinal system, such as the stomach and small intestine
  • a slightly increased risk of developing other types of cancer

People with AFAP develop fewer than 100 adenomatous polyps in their colon, and are usually diagnosed at a later age than those with classic FAP.

We recommend that people with FAP or AFAP have specialized cancer surveillance examinations. A genetic counselor or doctor experienced in caring for people with FAP or AFAP will talk with you about individualized recommendations, including risk-reducing procedures.

MYH-Associated Polyposis (MAP)

MAP is another inherited condition that can result in a large number of polyps. It is caused by mutations in both copies of the MUTYH gene. Typically, people with MAP develop fewer than 100 adenomatous polyps in their colon (similar to AFAP).

Unlike most hereditary cancer syndromes, MAP is a recessively inherited syndrome, which means an individual must inherit two MUTYH gene mutations — one from each parent — to develop MAP.

If both parents carry MUTYH mutations, there is a 25% chance that each of their children will inherit two MUTYH gene mutations and, therefore, have a risk of developing MAP.

People who have only one MUTYH mutation are called carriers. They may have a slightly increased risk of developing colorectal polyps or cancer, particularly if there is a history of colon cancer in your family.

We recommend that people with MAP pursue specialized cancer surveillance examinations and possibly consider risk-reducing procedures. A genetic counselor or doctor who is experienced in caring for people with MAP can make individualized recommendations for you.

Other Polyposis-Associated Genes
  • POLD1 and POLE gene mutations are associated with an increased risk for colon polyps and colorectal cancer. Families who have POLD1 and POLE gene mutations may have similar risks for polyps and cancers as families with FAP, AFAP, MAP, and Lynch syndrome. If one of your first-degree relatives (parent, sibling, or child) has this condition, you have a 50% chance of having inherited it.
  • GREM1 gene mutations are most common in individuals of Ashkenazi Jewish ancestry and cause an increased risk for various types of colon polyps and colorectal cancer. If one of your first-degree relatives (parent, sibling, or child) has this condition, you have a 50% chance of having inherited it.
  • MSH3 gene mutations are associated with having many colorectal polyps, as well as other noncancerous and cancerous tumors. Mutations in this gene are recessive, which means if both parents carry it, you have a 25% chance of developing it.
  • NTHL1 gene mutations are associated with colorectal polyposis, as well as other noncancerous and cancerous tumors. Mutations in this gene are recessive, which means if both parents carry it, you have a 25% chance of developing it.

It is important to note that these genes are newly described. The exact risks for cancer and polyps are still being investigated.

Hamartomatous Polyposis Genetic Conditions

Hamartomatous polyps, also called hamartomas, are noncancerous polyps that have an overall low risk of developing into cancer. There are several types of hamartomatous polyposis syndromes.

Peutz-Jeghers Syndrome (PJS)

PJS is a hereditary condition that may be found in people who develop polyps in their gastrointestinal tract. People with PJS are more likely to develop other types of cancer, including breast, stomach, and pancreatic cancers, and specific types of tumors in the ovaries, cervix, and testes. People with PJS often have small dark freckles on certain areas of the body, including around the mucus membranes, which may fade as a person gets older.

The gastrointestinal polyps that develop in PJS are called hamartomatous Peutz-Jeghers-type polyps. They grow mostly in the small intestine, colon, and stomach. The polyps can sometimes cause gastrointestinal bleeding, obstruction, and pain in the belly.

PJS is caused by a mutation in the STK11 gene. People with a first-degree relative (a parent, sibling, or child) with PJS have a 50% chance of having inherited the STK11 mutation.

We recommend that people with PJS pursue specialized cancer surveillance examinations and possibly consider risk-reducing procedures.  We recommend that people who have these mutations talk to a genetic counselor or doctor experienced in the care of people with PJS.

Juvenile Polyposis Syndrome (JPS)

JPS is a hereditary condition that causes polyps in the gastrointestinal tract. The gastrointestinal polyps that develop in JPS are called hamartomatous juvenile-type polyps. The polyps grow mostly in the colon, stomach, and small intestine. The polyps can sometimes cause gastrointestinal bleeding, obstruction, and pain in the belly.

The word “juvenile” does not refer to the development of the polyps during childhood — it refers to the specific subtype of polyp that develops. People with JPS are more likely to develop certain types of cancer, including colorectal, stomach, upper gastrointestinal, and pancreatic cancers.

A small group of people with JPS may also have a condition called hereditary hemorrhagic telangiectasia (HHT). People with HHT may have abnormal blood vessels in organs including the brain, lungs, and liver, which can cause bleeding, headaches, seizures, and other issues.

JPS is caused by a mutation in either the SMAD4 or BMPR1A genes. People with a first-degree relative (a parent, sibling, or child) with JPS have a 50% chance of having inherited the SMAD4 or BMPR1A mutation.

We recommend that people with JPS pursue specialized cancer surveillance examinations and possibly consider risk-reducing procedures. Individualized medical management recommendations should be discussed with a genetic counselor or doctor who is experienced in the care of people with JPS.

Cowden Syndrome

Cowden syndrome is a hereditary condition in which people are at risk for noncancerous and cancerous tumors of the breast, uterus, and thyroid. People with Cowden syndrome are also at risk of developing of hamartomatous polyps in the gastrointestinal tract. People with Cowden syndrome may have certain physical features, including a large head size (macrocephaly) and noncancerous lesions on the skin (trichelemmomas, lipomas, and papillomas).

Cowden syndrome may also be referred to as PTEN hamartoma tumor syndrome (PHTS), which encompasses variations of Cowden syndrome, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS). People with Cowden syndrome may also have autism or developmental delays.

Cowden syndrome is caused by a mutation in the PTEN gene. People with a first-degree relative (a parent, sibling, or child) with Cowden syndrome have a 50% chance of having inherited the PTEN mutation.

We recommend that people with Cowden syndrome pursue specialized cancer surveillance examinations and possibly consider risk-reducing procedures. Individualized medical management recommendations should be discussed with a genetic counselor or doctor who is experienced in the care of people with Cowden syndrome.