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   Colorectal Cancer Alliance of Central Massachusetts
   Genetics and Colorectal Cancer

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Introduction to Genetics and Cancer

All cancer, including colorectal cancer, is genetic in origin. What this means is that all cancer starts as a result of changes in our DNA or chromosome structure.

What is DNA?

DNA stands for deoxyribonucleic acid. DNA is a compound that contains instructions for the development and function of the body. These instructions are given at the cellular level. Every cell in the body, except the reproductive cells, holds a complete copy of an individual's DNA.

What are genes?

Genes are the basic unit of heredity . Genes are made up of different segments of DNA. Genes determine characteristics such as hair color, eye color, height, and to some extent, the types of diseases a person is at risk for. Not only are genes responsible for each person's unique characteristics, but genes also work to maintain the function of a living organism. For example, it is genes that tell the stomach to produce the enzymes needed to digest food, and it is genes that direct the body to heal a cut or scrape. Some genes work alone, while and some work together with other genes.

What are mutations?

In the ideal world, all genes would be free from defect and would function perfectly all the time. This is not the case, however. Both DNA and genes are susceptible to mutations. Mutations are changes that occur in the DNA sequence. Ultimately, these mutations impact the structure or function of the gene. Sometimes, mutations are harmless, but other times, mutations can lead to disease.

There are 2 types of genetic mutations: sporadic mutations and hereditary mutations.

Sporadic means that the mutations happen entirely by chance. Mutations can occur as a result of living our normal, daily lives. For example, the following circumstances can result in genetic mutations:

  • the normal aging process
  • exposure to the environment, such as the sun
  • exposure to other environmental substances, such as smoke, chemicals, or radiation

When sporadic mutations occur, they start by occurring in one cell of the body. As this cell replicates, the mutation continues to be reproduced. These new "mutated" cells, can then acquire more mutations. After a period of time, these mutations can result in cancer.

Hereditary mutations are inherited from parents and are passed down from generation to generation. Inherited mutations are present in each cell of the body, including the reproductive cells. As a result, people with a hereditary mutation can pass this mutation on to a child. A person who inherits a mutation that is associated with cancer, has a stronger likelihood of developing cancer at some point in his/her lifetime.

Hereditary mutations that lead to cancer are typically located in one of three genes - tumor suppressor genes, proto-oncogenes or cell-death genes. Together, these genes work to promote growth of new cells, allow old cells to die, and prevent cells from growing out of control. If one of these genes is not functioning properly, normal cell function can become disrupted and cancer can develop.

Genetics and Colorectal Cancer

From the genetic standpoint, colorectal cancer can be divided into three types:

  • sporadic colorectal cancer
  • familial colorectal cancer
  • hereditary colorectal cancer

The following graph shows the proportion of colorectal cancer that is accounted for by each type. (See Diagram 1)

Sporadic Colorectal Cancer

There are about 140,000 cases of colorectal cancer diagnosed each year. About 60% to 80% of these are considered sporadic in nature. "Sporadic" means that the cancer is thought to occur entirely by chance. Sporadic colorectal cancer is not caused by an inherited mutation. Instead, it is caused by an accumulation of sporadic gene mutations acquired throughout life. Because it takes several years for a series of genetic mutations to accumulate, sporadic colorectal cancer tends to occur at a later age, typically after the age of 50. As a result, all people over the age of 50 are considered at average risk for colorectal cancer.

Familial Colorectal Cancer

If colorectal cancer occurs in more than one family member, it could be due to multiple cases of sporadic cancer in the family. More likely, however, it is due to familial colorectal cancer. Familial colorectal cancer accounts for approximately 15% to 30% of all colorectal cancer cases.

Colorectal cancer is considered familial when there are two or more family members with a history of colorectal cancer or adenomatous polyps. In the case of familial colorectal cancer, no specific inherited gene mutation has been identified to explain the cancer. It is possible that colorectal cancer in this group results from a combination of genes and environmental factors.

People with a family history of colorectal cancer are considered at risk for familial colorectal cancer. They are also are at higher than average risk for getting colorectal cancer. It is recommended that people in this category start colon screening at a younger age than is generally recommended. If you have two or more family members with colorectal cancer or adenomatous polyps, you should talk to your doctor about appropriate colon cancer screening recommendations based on your family history.

Hereditary Colorectal Cancer

Like familial colorectal cancer, hereditary colorectal cancer is the result of inherited genetic mutations. In the case of hereditary colorectal cancer however, there is a specific gene mutation that has been identified. In some cases, hereditary colorectal cancer can also be diagnosed by specific clinical or laboratory criteria. Estimates vary, but it is believed that only about 5% of all colorectal cancer is caused by a known hereditary mutations.

People with hereditary colorectal cancer inherit a specific gene mutation from either their mother or father. As a result of having this inherited mutation, the person's likelihood for getting colorectal cancer increases dramatically. There are several types of hereditary colorectal cancer, but there are two that have been well-studied and are more common than the others. These two hereditary syndromes are called familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is sometimes also referred to as Lynch Syndrome.

Familial Adenomatous Polyposis (FAP)

Approximately 1% of patients diagnosed with colorectal cancer have FAP. FAP is characterized by the development of hundreds to thousands of adenomatous polyps in the colon and rectum. The term "polyposis" refers to the very large number of polyps that develop. Polyps themselves are benign, but adenomatous polyps are considered precancerous and can turn into colon or rectal cancer.

FAP is caused by a mutation in the APC gene. Scientists have determined that the APC gene is a critical gene in the development of adenomatous polyps and colorectal cancer. The normal APC gene is a tumor suppressor gene, a gene responsible for controlling and regulating cell growth. People with FAP inherit a mutation in the APC gene from a parent, and this mutation causes the gene to malfunction. Since the APC gene is so critical in the development of adenomatous polyps and colorectal cancer, people who have FAP develop hundreds to thousands of adenomatous polyps in the colon and rectum. As a result of having so many adenomatous polyps, people with FAP are almost certain to develop colorectal cancer at some point in their lives. Typically, adenomatous polyps begin developing in adolescence, and colorectal cancer develops by the age of 40 if left untreated.

FAP can also be associated with other cancerous and non-cancerous conditions. Some of the other cancers associated with FAP are:

  • thyroid cancer
  • medullablastoma (a type of brain cancer)
  • cancers of the small intestine and bile ducts
  • childhood hepatoblastoma (a type of liver tumor).

Non-cancerous conditions associated with FAP include:

  • sebaceous and epidermoid cysts
  • extra teeth
  • osteomas (a benign bone tumor)
  • desmoid tumors (a benign tumor)
  • an eye condition called congenital hypertrophy of the retinal pigment epithelium (CHRPE)

People with a family history of FAP, or who think they might be at risk for FAP, should consult with a healthcare professional trained in cancer genetics. There are specific screening guidelines and treatment options for people with FAP.

Hereditary non-polyposis colorectal cancer (HNPCC)

HNPCC is the most common hereditary colon cancer syndrome. It accounts for about 3% to 5% of all colorectal cancer cases. Despite the term "non-polyposis", polyps do occur in people with HNPCC. The number of polyps that develop, however, is much lower than that found in FAP.

HNPCC is caused by a mutation in one of several genes known as mismatch repair genes. Mismatch repair genes are a special type of tumor suppressor gene. The normal function of the mismatch repair gene is to ensure proper DNA replication during cell division. These genes act like the body's "spell-checker" during cell division and replication. Their job is to repair any mutations that might occur during this time. When there is a mutation in a mismatch repair gene, it does not function properly. As a result, mistakes made during DNA replication are not corrected, and can eventually lead to cancer development. People with HNPCC have about an 80% chance of developing colorectal cancer at some point in their lives. The average age of colorectal cancer development in HNPCC is 45 years of age.

HNPCC is also associated with other cancers, including:

  • endometrial cancer
  • stomach cancer
  • small bowel cancer
  • bile ducts cancer
  • ovarian cancer
  • pancreatic cancer
  • cancers of the urinary tract
  • sebaceous skin malignancies
  • glioblastoma, a type of brain cancer

People with a family history of HNPCC, or who think they might be at risk for HNPCC, should consult with a healthcare professional trained in cancer genetics. There are specific screening guidelines and treatment options for people with HNPCC.

Other hereditary colon cancer syndromes

FAP and HNPCC are the most common and most well-defined hereditary colorectal cancer syndromes, but there are others. These other hereditary colorectal cancer syndromes are rare, but include such names as:

  • MYH-associated polyposis
  • APC I1307K
  • Peutz-Jeghers Syndrome
  • Juvenile Polyposis Syndrome
  • Cowden Syndrome

Genetic Risk Assessment, Screening and Testing

Currently, genetic testing is available for FAP and HNPCC, as well as for some of the other hereditary cancer syndromes. Prior to testing, however, it is recommended that individuals at increased risk for cancer obtain a cancer genetic risk assessment. A genetic risk assessment involves meeting with a healthcare professional trained in genetics, such as a geneticist, a genetic counselor or a specially trained physician or nurse. Meeting with a trained genetics professional prior to testing is very important, as there are limitations to genetic testing. Most importantly, screening recommendations and treatment options are often different for people with hereditary cancer. Healthcare professionals who are specially trained in cancer genetics are better able to make recommendations that are appropriate based on your medical history and your family's medical history.

During a cancer risk assessment, the healthcare professional will:

  • take a detailed family history
  • explain in detail the genetics of specific syndromes
  • assess the appropriateness of genetic testing
  • coordinate testing with the appropriate laboratory
  • provide a detailed explanation of genetic test results, and
  • provide screening and treatment recommendations based on test results.

Symptoms of Other Hereditary Cancer Syndromes

The science of cancer genetics is constantly growing. Two hereditary colorectal cancer syndromes have been reviewed here, but there are several other inherited cancer syndromes. It is also likely that there are hereditary cancer syndromes that have not yet been discovered, but will be discovered in the coming years. Listed below are some conditions that put people at risk for cancer, or for being at risk of having a hereditary cancer syndrome.

Indicators of increased cancer risk include:

  • Cancer in two or more close relatives
  • History of the same cancer in two or more close relatives
  • Multiple primary tumors in the same individual
  • Family member with a diagnosis of cancer at an unusually young age
  • Presence of other tumors within the family that are part of a known cancer syndrome

If you or a family member has any of the above conditions, you may want to consider having a cancer risk assessment done.


Most major medical institutions offer genetics services, including family cancer risk assessments. In central Massachusetts, these services are provided by UMass Memorial in Worcester. Please visit their website at:

You can also find a genetic counselor in your area, by visiting the National Society of Genetics Counselors website:

Sporadic Colorectal Cancer 60-80%

Familial Colorectal Cancer 15-30%

Hereditary Colorectal Cancer 5%

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