Disease:Cancer - Colon and Rectum Cancer

The colon has 4 sections:

The first section is called the ascending colon. It begins where the small bowel attaches to the colon and extends upward on the right side of the abdomen.
The second section is called the transverse colon since it goes across the body from the right to the left side in the upper abdomen.
The third section, the descending colon, continues downward on the left side.
The fourth section is known as the sigmoid colon because of its 揝?or 搒igmoid?shape. At its end, the sigmoid colon joins the rectum, which in turn joins the anus, or the opening where waste matter, or stool, passes out of the body.

The wall of each of these sections of the colon and rectum has several layers of tissue. Colorectal cancer starts in the innermost layer and can grow through some or all of the other layers. Knowing a little about these layers is important, because the stage (extent of spread) of a colorectal cancer depends to a great degree on how deeply it invades into these layers. For more information, please refer to the staging section of this document.

Colon cancer and rectal cancer, collectively known as colorectal cancer, have many features in common. They will be discussed together in this document except for the section about treatment, where they will each be discussed separately.

In most people, colorectal cancers develop slowly over a period of several years. Before a cancer develops, a growth of tissue or tumor usually begins as a non-cancerous polyp, which may eventually change into cancer. A polyp develops on the lining of the colon or rectum. Certain kinds of polyps, called adenomatous polyps or adenomas, are types that have the potential to become cancerous.

There are other kinds of polyps called hyperplastic and inflammatory polyps. Inflammatory polyps and hyperplastic polyps, in general, do not become pre-cancerous. But some doctors think that some hyperplastic polyps can become pre-cancerous or might be a sign of a greater likelihood of developing adenomatous polyps and cancer, particularly if they grow in the right or ascending colon. Another kind of pre-cancerous condition is called dysplasia. This is usually seen in people with diseases, such as ulcerative colitis or Crohn抯 colitis, which cause chronic inflammation of the colon.

Once cancer forms within a polyp, it can eventually begin to grow into the wall of the colon or rectum. When cancer cells are in the wall, they can then grow into blood vessels or lymph vessels. Lymph vessels are thin, tiny channels that carry away waste and fluid. They first drain into nearby lymph nodes, which are bean-shaped structures that help fight against infections. After they spread into blood or lymph vessels, the cancer cells can travel to distant parts of the body. This process of spread is called metastasis.

More than 95% of colorectal cancers are adenocarcinomas. These are cancers of the glandular cells that line the inside layer of the wall of the colon and rectum. The information in this document is about this type of cancer. Other less common types of tumors may also develop in the colon and rectum, such as:

carcinoid tumors – these tumors develop from specialized hormone-producing cells of the intestine.
gastrointestinal stromal tumors – these tumors develop from specialized cells in the wall of the colon called the "interstitial cells of Cajal." Some are benign (non-cancerous); others are malignant (cancerous). Although these cancers can be found anywhere in the gastrointestinal tract, they are unusual in the colon.
lymphomas – these are cancers of immune system cells that typically develop in lymph nodes but also may start in the colon and rectum or other organs.

Do We Know What Causes Colorectal Cancer?

Although we do not know the exact cause of most colorectal cancers, there are certain known risk factors, and there is a great deal of research going on to find answers to the question.

A small percentage of colorectal cancers are known to be caused by inherited gene mutations (changes in DNA). Recently, scientists have discovered many of these DNA changes, learned how they change the growth control of cells, and determined how the changes can be detected in people before colorectal cancers develop.

Changes in a gene called APC, for example, are responsible for familial adenomatous polyposis (FAP) and Gardner syndrome. This gene is normally responsible for slowing the growth of cells. In patients who have inherited changes in the APC gene, this "brake" on cell growth is turned off and hundreds of polyps develop in the colon. Over time, cancer will nearly always develop in one or more of these polyps because of new gene mutations in the cells of the polyps. We all have these new gene mutations. But they rarely lead to cancer because the cells die instead of continuing to grow as they do when the APC "brake" is turned off.

In addition, a defective DNA repair mechanism is responsible for hereditary nonpolyposis colon cancer (HNPCC). Cells must make a new copy of their DNA each time they divide. Occasional errors are made in copying the DNA code. Fortunately, cells have DNA repair enzymes that act like proofreaders or "spell checkers." Mutations in the DNA repair enzyme genes in HNPCC allow DNA errors to go uncorrected. Mutations in at least four different genes can lead to errors in repair. These errors will sometimes affect growth-regulating genes. This can lead to the development of cancer.

Tests are available that can detect gene mutations associated with FAP and HNPCC. If you have a family history of colorectal cancer or any of the associated cancers discussed above, you should ask your doctor about genetic counseling and genetic testing. The American Cancer Society recommends discussing genetic testing with a qualified genetic counselor before genetic testing is done.

Most people with colorectal cancer do not have an inherited gene mutation. Instead, the gene mutations develop spontaneously. Many doctors think the first mutation occurs in the APC gene. This leads to an increased growth of colorectal cells because of the loss of this 揵rake?molecule. Another mutation then occurs in the gene called K-RAS and causes this gene to become an 揳ccelerator?of cell growth. Many other mutations eventually occur and lead the cells to grow uncontrollably.

Can Colorectal Cancer Be Prevented?

What Are the Risk Factors for Colorectal Cancer?

A risk factor is anything that increases your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor for skin cancer, and smoking is a risk factor for cancers of the lungs, larynx, mouth, throat, esophagus, kidneys, bladder, colon, and several other organs. Researchers have identified several risk factors that increase a person's chance of developing colorectal polyps or colorectal cancer.

Age: While younger adults can develop colorectal cancer, your chances of developing colorectal cancer increase markedly after age 50. Over 90% of people diagnosed with colorectal cancer are older than 50.

A personal history of colorectal cancer: If you have had colorectal cancer, even though it has been completely removed, you are more likely to develop new cancers in other areas of the colon and rectum. The chances of this happening are greater if you had your first colorectal cancer when you were age 60 or younger.

A personal history of colorectal polyps: If you have had an adenomatous-type polyp, you are at increased risk of developing colorectal cancer. This is especially true if the polyps are large or if there are many of them.

A personal history of inflammatory bowel disease: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a condition in which the colon is inflamed over a long period of time. If you have IBD, your risk of developing colorectal cancer is increased. If you have had IBD for 8 years or more, you should undergo colonoscopy testing for colorectal cancer on a frequent basis. Based on your individual case, your doctor may recommend a colonoscopy every 1 to 2 years. Often the first sign that cancer may be developing is called dysplasia. Dysplasia is a term that refers to abnormal cells that have the potential to progress to cancer. Inflammatory bowel disease is different than irritable bowel syndrome (IBS), which does not carry an increased risk for colorectal cancer.

A family history of colorectal cancer: Some cancers can 搑un in the family?because something in the environment has contributed to the development of cancer and/or because certain family members were born with, or inherited, an increased genetic susceptibility to cancer. While most colorectal cancers occur in people without a family history of colorectal cancer, those with a family history of colorectal cancer or adenomatous polyps in any first-degree relative younger than age 60, or in 2 or more first-degree relatives at any age are considered at increased risk for the disease. (First-degree relatives are defined as parents, siblings, and children.)

Familial disease
About 15% of people who develop colorectal cancer have disease that is familial. People who have a strong family history of colorectal cancer (as defined above), especially if the relatives are affected before the age of 60, are considered at increased risk of developing this disease. People diagnosed with adenomatous polyps or cancer should inform other family members, and individuals with a family history of colorectal cancer need to talk with their doctor about the possible need to begin colorectal cancer screening at an age younger than that recommended for the general population (50 years).

Inherited disease
About 3% to 5% of people who develop colorectal cancer have an inherited genetic susceptibility to the disease. Most of these are associated with the inherited colorectal cancer syndrome, called hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome. A lesser number of colorectal cancer cases are associated with the inherited syndrome, called familial adenomatous polyposis (FAP).

FAP is a disease where people typically develop hundreds of polyps in their colon and rectum. Usually this occurs between the ages of 5 and 40. Cancer usually develops in 1 or more of these polyps beginning at age 20. By age 40, almost all people with this disorder will have developed cancer if preventive surgery is not done. FAP is sometimes associated with Gardner syndrome, a condition that involves benign (non-cancerous) tumors of the skin, soft connective tissue, and bones. About 1% of all colorectal cancers are due to FAP.

Hereditary nonpolyposis colon cancer (HNPCC) is another clearly defined genetic syndrome. It accounts for 3% to 4% of all colorectal cancers. This syndrome also develops when people are relatively young. These people have polyps, but they only have a few, not hundreds as in FAP. Women with this condition also have a very high risk of developing cancer of the endometrium (lining of the upper part of the uterus). Other cancers associated with HNPCC include cancer of the ovary, stomach, small bowel, pancreas, kidney, ureters (tubes that carry urine from the kidneys to the bladder), and bile duct.

Doctors have found that most families with HNPCC have certain characteristics:

At least 3 relatives have either colorectal cancer or endometrial cancer or one of the other cancers seen with HNPCC.

Two successive generations are involved.

At least 1 relative had their cancer when they were younger than age 50.

At least 2 of the people are first-degree relatives.

These are called the Amsterdam criteria. If any of these hold true for your family, then you might want to seek genetic counseling. But even if your family history satisfies the Amsterdam criteria, it doesn抰 mean you have HNPCC. Only about 60% of families who meet the Amsterdam criteria have HNPCC. The other 40% do not; and although their colorectal cancer rate is higher than normal (about 2 times), it is not as high as that of people with HNPCC (about 6 times).

A second set of criteria for HNPCC, which has been recently revised, is called the Bethesda criteria. These are used to determine whether a person with colorectal cancer should have his or her cancer tested for genetic changes that are seen in HNPCC. These criteria include at least one of the following:

The person is younger than 50 years.

The person has or had another cancer (endometrial, stomach, pancreas, ovary, kidney or ureters, bile duct) that is associated with HNPCC.

The person is younger than 60 years and the cancer has certain characteristics seen with HNPCC when viewed under the microscope.

A first-degree relative has been diagnosed with colorectal cancer and a non-colorectal cancer often seen in HNPCC carriers (endometrial, stomach, pancreas, ovary, kidney, ureters, or bile duct) and one of these occurred when the person was younger than 50 years.

The person has 2 or more second-degree relatives who had colorectal cancer and an HNPCC-related tumor at any age.

If a person with colorectal cancer meets the Bethesda criteria, genetic testing will be needed to confirm an inherited HNPCC-associated genetic mutation. The majority of people who meet the Bethesda criteria do not have HNPCC.

Doctors should also be suspicious of HNPCC if, instead of colorectal cancer, the family members have other cancers associated with this gene mutation. These are endometrial cancers, ovarian cancers, small bowel cancers, or cancer of the lining of the kidney or the ureters. Even if one of these cancers has been found, 1 family member younger than age 50 must have been diagnosed with colorectal cancer before a diagnosis of HNPCC is considered.

Accurate identification of families with these inherited syndromes is important. Then doctors can recommend specific steps, such as screening and other preventive measures, at an early age. Because several types of cancer can be associated with inherited colorectal cancer syndromes, all people should check their family medical history for polyps or any type of cancer. Those who develop polyps or cancer should inform other family members. People with a family history of colorectal polyps or cancer should consider genetic counseling, to review their family medical tree and determine whether genetic testing may be right for them. This will help them to make decisions about getting screened and treated at an early age.

Ethnic background: Some studies have concluded that Jews of Eastern European descent (Ashkenazi Jews) have the highest colorectal cancer risk of any ethnic group in the world. Recent research has found several genetic mutations leading to increased risk of colorectal cancer in this group. The most common of these DNA changes is present in about 6% of American Jews. In one study, about 10% of colorectal cancers in Jews of Eastern European descent were associated with this change, called the I1307K APC mutation. However, the genetic mutations discovered so far do not fully account for the increased number of colorectal cancers in Ashkenazi Jews.

Race: African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the United States. The reason for this is not yet understood.

A diet mostly from animal sources: A diet that is high in fat, especially fats from animal sources, can increase your risk of colorectal cancer. Over time, eating a lot of red meats and processed meats can increase colorectal cancer risk. The American Cancer Society recommends choosing most of your foods from plant sources and limiting your intake of high-fat foods such as those from animal sources. The American Cancer Society also recommends eating at least 5 servings of fruits and vegetables every day and several servings of other foods from plant sources, such as breads, cereals, grain products, rice, pasta, or beans. Many fruits and vegetables contain substances that interfere with the process of cancer formation.

Physical inactivity: If you are not physically active, you have a greater chance of developing colorectal cancer.

Obesity: If you are very overweight, your risk of dying from colorectal cancer is increased.

Smoking: Recent studies indicate that smokers are 30% to 40% more likely than non-smokers to die from colorectal cancer. Smoking may be responsible for causing about 12% of fatal colorectal cancers. Almost everyone knows that smoking causes cancers in sites in the body that come in direct contact with the smoke, such as the mouth, larynx, and lungs. However, some of the cancer-causing substances are swallowed and can cause digestive system cancers, such as esophageal and colorectal cancer. Some of these substances are also absorbed into the bloodstream and can increase the risk of developing cancers of the kidneys, bladder, cervix, and other organs.

Alcohol intake: Colorectal cancer has been linked to the heavy use of alcohol. While some of this may be due to the effects of alcohol on folic acid in the body, it still would be wise to avoid heavy alcohol use.

Diabetes: People with diabetes have a 30% increased risk of developing colorectal cancer. They also tend to have a worse prognosis after diagnosis.

Factors with Uncertain, Controversial, or Unproven Effects on Colorectal Cancer

Night-shift work: Results of one single study suggest working a night shift at least 3 nights a month for at least 15 years may increase the risk of colorectal cancer in women. The study authors suggested this might be due to changes in melatonin (a hormone that responds to changes in light) levels in the body. More research is needed to confirm or refute this finding, however.

Other cancers and their treatment: A recent report on testicular cancer survivors found that these men had a higher rate of colorectal cancer. Men who receive radiation therapy for prostate cancer have been reported to have a higher risk of rectal cancer.