What are genes?

Genes carry small individual collections of information within each cell of the human body. Each gene is made of a unique sequence of DNA. Researchers working on the Human Genome Project have estimated that there are as many as 30,000 different genes in each cell. Genes are packaged onto chromosomes. There are 23 pairs of chromosomes in each cell. One chromosome of each pair is inherited from the person's father and one from the person's mother.

Genes control how a cell functions, including how quickly it grows, how often it divides, and how long it lives. To control these functions, genes produce proteins that perform specific tasks and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the proper function for the cell.

What role do genes play in colorectal cancer?

Cancer begins when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

A person may either be born with a genetic mutation in all of their cells (germline mutation) or acquire a genetic mutation in a single cell during his or her lifetime. An acquired mutation is passed on to all cells that develop from that single cell (called a somatic mutation). Somatic mutations can sometimes be caused by environmental factors, such as cigarette smoke. Most colorectal cancers (about 95%) are considered sporadic, meaning that the damage to the genes occurs by chance after a person is born. Inherited colorectal cancers are less common (about 5%) and occur when gene mutations are passed within a family from one generation to the next.

What are the chances a damaged gene is inherited?

Every cell usually has two copies of each gene: one inherited from the mother and one inherited from the father. Hereditary colorectal cancer usually follows an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting the disease. This means that a parent with a gene mutation may pass on a copy of the normal gene or a copy of the gene with a mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a gene mutation also has a 50% chance of having the same mutation.

What is a person's average risk for colorectal cancer?

A person with an average risk of colorectal cancer has about a 5% chance of developing colorectal cancer. Men have a slightly higher risk of developing colorectal cancer than women.

How common is colorectal cancer?

Colorectal cancer is the third most common cancer among both men and women in the United States. It is also the third most common cause of cancer death among men and women separately (and the second most common cause of cancer death total if men and women are combined) in the United States. In 2008, approximately 148,810 adults (77,250 men and 71,560 women) in the United States will be diagnosed with colorectal cancer. These numbers include the 108,070 adults diagnosed with colon cancer and the 40,740 adults diagnosed with rectal cancer. An estimated 49,960 deaths (24,260 men and 25,700 women) will occur from this disease this year.

How can a person know if he or she has inherited a genetic mutation that increases his or her risk of colorectal cancer?

Only genetic testing can determine whether a person has a genetic mutation. Most experts strongly recommend that people considering genetic testing first consult a genetic counselor. Genetic counselors are trained to explain the risks and benefits of genetic testing.

For more information, read Genetic Testing and What to Expect When Meeting With a Genetic Counselor.

How does a person know if colorectal cancer runs in the family?

Colorectal cancer may run in the family if first-degree relatives (parents, brothers, sisters, children) or many other family members (grandparents, aunts, uncles, nieces, nephews, grandchildren, cousins) have had colorectal cancer. This is especially true when family members are diagnosed with colorectal cancer before age 50.

What is a person's risk if colorectal cancer runs in the family?

If a person's first-degree relatives developed colorectal cancer younger than age 50, his or her risk of colorectal cancer is nearly double the average risk of colorectal cancer. The risk increases if other close relatives have colorectal cancer.

Which inherited genetic mutations raise the risk of colorectal cancer?

There are several genes associated with an increased risk of colorectal cancer. Some of the most common hereditary colorectal cancer syndromes are described below.

Hereditary non-polyposis colorectal cancer (HNPCC). HNPCC, sometimes called Lynch syndrome, accounts for approximately 3% to 5% of all colorectal cancers. The risk of colorectal cancer in families with HNPCC is 80%, which is several times higher than the average risk. The average age for a person with HNPCC to be diagnosed with colorectal cancer is 45. For women with HNPCC, the risk of uterine cancer is about 20% to 60% and the risk of ovarian cancer is about 9% to 12%. In addition, people with HNPCC also have an increased risk of cancers of the stomach, small intestine, liver, bile duct, urinary tract, and the brain and central nervous system. There may also be some increased risk of breast cancer.

Mutations in the MLH1, MSH2, MSH6, and PMS2 genes are the most frequent cause of HNPCC. The genes associated with HNPCC are mismatch repair genes. A mismatch repair gene makes proteins that repair DNA mistakes that occur as a cell divides. If one of these genes has a mutation, the mistakes cannot be repaired, leading to damaged DNA and an increased risk of cancer. Although multiple genes have been linked to HNPCC, most families with HNPCC have a mutation in only one of the genes. Genetic testing is available for the MLH1, MSH2, and MSH6 genes. The PMS2 gene is only tested as part of a clinical trial.

Because colorectal cancer is one of the most treatable forms of cancer if found early, people diagnosed with HNPCC, or those who may have an increased risk based on their family history, often benefit from increased screening with annual colonoscopy examinations.

To prevent colorectal cancer, a prophylactic colectomy (the surgical removal of the entire colon) may decrease the risk of colorectal cancer for patients who have an increased risk. Drugs that may stop a tumor from forming are being tested to prevent HNPCC-related colon cancers.

For more information, read the Cancer.Net Guide to Hereditary Non-Polyposis Colorectal Cancer.

Familial adenomatous polyposis (FAP). FAP accounts for about 1% of colorectal cancers. People with FAP often develop hundreds to thousands of polyps (a growth in the colon or rectum) that are initially noncancerous, but there is almost a 100% chance that the polyps will develop into cancer if not treated. Most people with FAP develop polyps by age 35, with the average age in the mid-teens. The risk of a person with FAP developing colorectal cancer by age 45 is 87%. People with FAP also have an increased risk of other types of cancers including stomach, small intestine, pancreas, thyroid, and hepatoblastoma (liver cancer that usually occurs in early childhood). Although FAP follows an autosomal dominant inheritance pattern, approximately 30% of people with FAP have no family history of the condition.

People with a variation of FAP, called attenuated familial adenomatous polyposis (AFAP), often develop fewer polyps, usually around 30 total. For people with AFAP, colorectal cancer may not develop until around age 50.

FAP and AFAP are caused by a mutation on the APC gene, which is a tumor suppressor gene. Tumor suppressor genes make proteins that suppress tumor formation by limiting cell growth. Mutations in tumor suppressor genes result in a loss of the ability to restrict tumor growth and, as a result, cancer can develop. About 6% of people with Ashkenazi Jewish heritage have a specific mutation in the APC gene, called I1307K, which increases the risk of colorectal cancer. Genetic testing for the APC gene is available.

Since polyps can be found at an early age, people with FAP or who may have FAP should talk with their doctor about regular screening, such as a yearly sigmoidoscopy beginning around ages 10 to 12. A colectomy may be recommended to decrease the risk of cancer. Continued screening for polyps in the rectal area and the upper digestive tract is recommended after the colon is removed.

For more information, read the Cancer.Net Guide to Familial Adenomatous Polyposis and the Cancer.Net Guide to Attenuated Family Adenomatous Polyposis.

Muir-Torre syndrome. Muir-Torre syndrome is a type of HNPCC. In addition to increasing the risk of colorectal cancer and the other types of cancer associated with HNPCC, people with Muir-Torre syndrome often develop skin changes in adulthood. These skin changes are usually not cancerous.

For more information, read the Cancer.Net Guide to Muir-Torre Syndrome.

Gardner syndrome. Gardner syndrome is a type of FAP. In addition to an increased risk of colon polyps and other FAP-related cancers, people with Gardner syndrome may also have osteomas (bony tumors) of the jaw, extra teeth, and soft tissue tumors including lipomas (fatty tissue) and fibromas (fibrous tissue).

For more information, read the Cancer.Net Guide to Gardner Syndrome.

Turcot syndrome. Turcot syndrome is a type of both HNPCC and FAP. People with Turcot syndrome have an increased risk of colorectal cancer and brain tumors. Medulloblastoma, a type of brain tumor, is more common for people who have a genetic mutation associated with FAP. Glioblastoma, another type of brain tumor, is more common for people who have a genetic mutation associated with HNPCC.

For more information, read the Cancer.Net Guide to Turcot Syndrome.

MYH-associated polyposis (MAP). People with MAP often develop multiple colon polyps that increases their risk of colorectal cancer. MAP is caused by a mutation on the MYH gene and follows an autosomal recessive inheritance pattern, in which a mutation needs to be present in both copies of the gene in order for a person to have an increased risk of getting that disease. Genetic testing for MYH gene mutations is available. Because many people with MYH gene mutations are thought to have FAP or AFAP, genetic testing may be recommended for people with multiple colon polyps who do not have mutations on the APC gene.

For more information, read the Cancer.Net Guide to MYH-Associated Polyposis.

Peutz-Jeghers syndrome (PJS). People with PJS have a 40% risk of developing colorectal cancer. People with PJS often have multiple hamartomatous polyps, which are normal-appearing growths in the digestive tract that become noncancerous tumors. People with PJS also have increased pigmentation (dark spots on the skin) on the face and hands. The increased pigmentation often appears in childhood and fades over time. Families with PJS also have an increased risk of breast, uterine, ovarian, and lung cancers. The gene associated with PJS is called STK11. The STK11 is a tumor suppressor gene, and genetic testing for the STK11 gene is available.

For more information, read the Cancer.Net Guide to Peutz-Jeghers Syndrome.

Juvenile polyposis syndrome (JPS). People with JPS often have multiple juvenile polyps (a specific type of polyp) in the colon or other parts of the digestive system. Most people with JPS develop some polyps by age 20. Because of these polyps, people with PJS have an increased risk of colorectal, stomach, small intestine, and pancreatic cancers. Overall, people with PJS have a 9% to 50% risk of developing cancer. Two genes are associated with JPS, called BMPR1A and SMAD4, and genetic testing is available.

For more information, read the Cancer.Net Guide to Juvenile Polyposis Syndrome.

What is a person's risk level?

In addition to family history, other environmental and lifestyle factors may increase the risk of colorectal cancer. Discussing family history and personal risk factors with a doctor can help a person better understand his or her risk. People with a higher than average risk may benefit from genetic counseling and early detection strategies.

A risk factor is anything that increases a person's risk of developing cancer. Having a particular genetic mutation linked to colorectal cancer cannot predict that a person will develop cancer. Controllable risk factors, such as eating a balanced diet, maintaining a healthy weight, exercising, limiting alcoholic beverages, and avoiding tobacco products also play a role. Most people who develop colorectal cancer have few known risk factors. Research to better understand the link between genetic mutations and colorectal cancer is ongoing. Talk with a doctor for more information about risk factors, prevention, and screening for colorectal cancer.

Additional Resources

Genetics

Guide to Colorectal Cancer

Cancer.Net Feature: Chemoprevention