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Hereditary Colorectal Cancer Overview

Hereditary colorectal cancer refers to any cancer of the colon and rectum that results from an inherited syndrome passed on through genetics.

Key Info

  • About 5-10% of all colorectal cancers diagnosed each year in the US are hereditary
  • Hereditary colorectal cancer syndromes can affect organs beyond the colon and rectum
  • Screening tests like colonoscopy can help monitor and manage these syndromes

Causes

Hereditary colorectal cancers are caused by genetic mutations passed on between generations within a family. Almost all human genetic material is stored in DNA molecules. The genes in our DNA work like a cookbook for the body—they contain the recipes for all the body’s proteins. If one of the “recipes” in the DNA is wrong (the gene is not working), the protein that was supposed to be produced might not work properly. If the protein is not working, it can lead to disease.

DNA and Genes

A gene is a sequence of DNA that holds the code for a protein. That code uses combinations of 4 nucleotide bases (adenine, thymine, cytosine, guanine). Three bases in a row make up a codon, a code for an amino acid. When multiple amino acids are strung together, it forms a polypeptide—the basis for a protein.

Producing proteins is a tricky business. The body sends a signal to a cell that it needs a protein. The signal is transmitted to the nucleus of the cell, where the DNA lives. The gene that makes the required protein is switched on and the protein is made and does its job. When the protein is no longer needed, the cell gets a signal to switch off that gene. If any of the genes in this complicated system of signaling and response stop working, the whole system can go out of whack. When this interrupts the signals that control cell growth, the result is that cells can grow rapidly and inappropriately.

Genes and Cancer

Cancer is a disease of cell growth. In the colon, cells grow fast, with a life cycle of 4 to 5 days. The growth of cells is tightly controlled by genes that stimulate (called oncogenes) and genes that inhibit (called tumor suppressor genes). Think of oncogenes as an accelerator and the suppressor genes as a brake. If the accelerator gets stuck or the brake doesn’t work, the car goes out of control. Cells growing out of control can turn into cancers.

DNA reproduces each time cells divide. DNA has 3 billion bases and 30,000 genes. It is inevitable that mistakes happen when such a complex molecule replicates. There are multiple proteins that detect the mistakes and correct them. When it is these DNA repair genes that don’t work, mistakes in DNA replication are not corrected and become mutations. When the mutation that sabotages DNA repair is in every cell in a person’s body, the whole body is liable to get thousands of mutations, cells grow faster than usual and cancers start to pop up.

Each of the syndromes of Hereditary Colorectal Cancer is associated with a particular gene or set of genes that repair mistakes in the DNA.

Hereditary Colorectal Cancer Syndromes

A syndrome is a collection of disorders that are all tied to a single cause. Doctors typically classify colorectal cancer syndromes as polyposis syndromes (those that cause multiple polyps to grow within the gut) and non-polyposis syndromes. 

Polyposis Syndromes

  • Familial adenomatous polyposis
  • MUTYH /NTHL1 associated polyposis
  • Polymerase proofreading associated polyposis
  • Serrated Polyposis
  • Juvenile polyposis
  • Peutz-Jeghers polyposis
  • PTEN Hamartoma Tumor Syndrome(Includes Cowden Syndrome, Bannayan Ruvalcaba Riley Syndrome, Proteus Syndrome)
  • Hereditary mixed polyposis

Non-Polyposis Syndromes

  • Hereditary Non Polyposis Colorectal Cancer (aka Lynch Syndrome)
  • Familial Colorectal Cancer Type X
  • Tumor Lynch
  • Bub1

Familial adenomatous polyposis (FAP) is the most common of the polyposis syndromes, while Hereditary Non Polyposis Colorectal Cancer (HNPCC), or Lynch Syndrome, is the most common of the non-polyposis syndromes and is the most common form of hereditary colon cancer in general.

Diagnosis

The best way to diagnose hereditary colorectal cancer syndromes is by genetic testing. Although we do not have the capacity to test everyone’s DNA for every gene, we do have cheap genetic testing available that will rule out or diagnose most of these syndromes. 

Current guidelines recommend that people with the following characteristics should receive genetic testing:

Indications for Genetic testing adapted from the CGA recommendations, 2020

  1. Having more than 10 total colorectal adenomas or polpys
  2. Being diagnosed with colorectal cancer before age 50
  3. Having colorectal cancer and at least one first degree relative with colorectal or endometrial cancer
  4. Having a mismatch repair (MMR) deficient colorectal cancer, not attributed to MLH1 promoter methylation
  5. Having a PREMM5 score ≥ 2.5% or MMRpro or MMRpredict score ≥ 5%
  6. Having Multiple Lynch syndrome primary tumors
  7. Having 3 or more total gastrointestinal hamartomatous polyps

Genetic Testing Process

The genetic testing process begins with an appointment for pre-test counseling with a genetic counselor. This is an educational session to better understand what genetic testing can and can’t do, and to learn about the social and financial implications of genetic testing.

The genetic test itself is done by collecting a sample of blood or saliva. The DNA in this sample is checked for all known genes associated with colon or rectal cancer. Results usually take 2 to 3 weeks to become available.

Treatment

People who test positive for a cancer-causing DNA mutation are typically recommended to get a colonoscopy every year. Colonoscopies allow doctors to check for polyps and cancer within the colon.

For people that test positive and have already had colon cancer or polyps, surgery to remove part or all of the colon may be the best option to avoid more cancer. 

Because these syndromes are genetic and therefore run in families, those who test positive should encourage their relatives to consider genetic testing as well.

Next Steps

If you or a loved one is dealing with hereditary colorectal cancer, we can help. Our dedicated Hereditary Colorectal Cancer Center is here to help at every step of the way, from diagnosis and genetic testing to surgery and ongoing monitoring. 

Call us at (212) 342-1155 or request an appointment online today.

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