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Can I inherit colon cancer? A look at colon cancer genes

Are you predestined to have colon cancer? Do you have colon cancer genes you don’t know about?

In 1895 a seamstress told Dr. Aldred Scott Warthin that many of her family members over many generations died of cancer. The seamstress was worried she too would die of cancer. She did. The seamstress died of endometrial cancer. The seamstress had 10 siblings; 2 had endometrial cancers, 2 had stomach cancers, and 1 had abdominal cancer.

Dr. Warthin called the family- Family G.

In the early 1960s, Dr. Henry T. Lynch arranged a family reunion for the seamstress family (Family G) in Michigan. He collected information on over 650 family members. Ninety-five had developed cancer. Most of the cancers were in the colon, stomach and uterus.

These cancers were inherited in an autosomal dominant pattern. This means a person with the abnormal gene has a 50 percent chance of passing the abnormal gene to each child. A child also has a 50 percent chance of not inheriting the abnormal gene. A child only needs 1 abnormal copy to have the disease.

This discovery led to what is now known as Lynch syndrome.

So can you inherit colorectal cancer? The answer is yes.

When to suspect inherited colorectal cancer

  • Colorectal cancer at a young age. Bowel cancer in a person less than 45 years old should raise the suspicion for genetic cancer.
  • Many family members with colorectal cancer or colon polyps.
  • Multiple different cancers in one person.
  • Many different cancers across multiple generations.
  • Presence of ten or more adenomatous or serrated polyps. 

 

Main types of inherited colon cancer 

There are different forms of inherited colon cancer syndromes. Some are associated with polyposis (the presence of many polyps) and others are not.

Lynch syndrome 

Lynch syndrome is the most common cause of inherited colon cancer. It is also called hereditary nonpolyposis colorectal cancer. The most common extra-colonic cancer associated with Lynch syndrome is endometrial cancer. Individuals with Lynch syndrome may be identified using the Amsterdam criteria or the Revised Bethesda criteria.

Lynch syndrome is caused by germline mutation in one of these DNA mismatch repair genes – MLH1, MSH2, MSH6, PMS2. It is also caused by loss of expression of MSH2 due to deletion in the EPCAM gene (previously known as TCSTD1).

You can use this PREMM model calculator to determine your risk for Lynch syndrome.

Familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is a form of inherited colon cancer syndromes marked by the presence of multiple colorectal adenomatous polyps. It is caused by mutations in the tumor suppressor gene, Adenomatous Polyposis Coli (APC), located on chromosome 5q21-q22.

It is inherited in an autosomal dominant pattern. However, up to 25% of FAP cases are due to new APC mutations and these people do not have a family history of FAP.

There are 2 types of FAP- Classic FAP and attenuated FAP. Patients with classic FAP typically have 100-1000 adenomatous polyps. Polyps usually start between the age of 8-15 years. Colorectal cancer occurs in nearly 100% of these patients. Most of the cancers occur in the rectum and sigmoid area. 

Attenuated FAP is a milder form of FAP. Patients have smaller number of polyps; usually between 10-99 adenomatous polyps. Polyps usually start at a later age in the 40s.  Colorectal cancer occurs in about 80% of these patients.

FAP is also associated with different variants. Gardner syndrome is associated with several extracolonic manifestations like desmoid tumors, sebaceous or epidermoid cysts, lipomas, osteomas, fibromas, extra teeth, gastric polyps, angiofbromas, and CHRPE.

Turcot syndrome also known as brain tumor polyposis syndrome is associated with brain tumors especially medulloblastomas and gliomas.

MUTYH-associated polyposis 

MUTYH-associated polyposis is an autosomal recessive polyposis syndrome due to mutations in the MUTYH gene. Patients with this disorder may be homozygous or compound heterozygous for the mutations in the MUTYH gene. This syndrome is seen in 7-13% of patients with >100 adenomas during colonoscopy.

Also, the disease is found in 14-40% of patients with 10-99 adenomatous polyps.

The life-time risk for colorectal cancer is 70-75% and almost 60% of the patients already have cancer at the time of diagnosis.

Other types of inherited colon cancer 

Oligopolyposis

NTHL1-associated polyposis  

Juvenile polyposis syndrome 

PTEN hamartoma tumor syndromes (Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome). 

Peutz-Jeghers syndrome 

Hereditary mixed polyposis syndrome 

Serrated polyposis syndrome/Hyperplastic polyposis syndrome 

Familial colorectal cancer type X

Colon cancer genes

Cancer GeneDisease (Syndrome)Hereditary Pattern
MLH1, MSH2, MSH6, PMS2Lynch syndromeDominant
EPCAM (TACSTD1)Lynch syndromeDominant
MUTYH (MYH)MUTYH-associated polyposisRecessive
POLD1, POLEOligopolyposisDominant
APCFamilial adenomatous polyposis (FAP)
Dominant
TP53 (p53)Li-FraumeniDominant
STK11 (LKB1)Peutz-Jeghers syndrome (PJS)Dominant
PTENCowdenDominant
BMPR1Ajuvenile polyposis syndrome (JPS)Dominant
SMAD4 (MADH/DPC4)juvenile polyposis syndrome (JPS)Dominant

 

How can I find out if I have colon cancer genes?

Know your family history. A person without a family history of adenomatous colon polyp or colorectal cancer has a 4% risk for colorectal cancer by age 79. The risk goes up to 8% if you have one first-degree relative (FDR) with colorectal adenoma polyp. If you have one FDR with colorectal cancer, the risk is 9%. If the affected FDR was diagnosed with colorectal cancer before age 45 years, then the risk is 15%.

A person with more than one FDR with colorectal cancer has a 16% risk of colorectal cancer by age 79.

Not all cancer genes have been identified, so knowing your family history is very important.

Talk to your physician. If you’re worried about having a colorectal cancer gene, talk to your physician. She will guide you on the steps you need to take.

Direct to consumer genetic testing. Many companies now offer direct to consumer genetic testing. With these companies, you can order your own genetic testing yourself. Many offer specific genetic testing and others offer tests for all known cancer genes. Some of the companies offering genetic testing are color, 23andme, and Progenity.

 

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