Introduction
It's likely that you know someone who has been affected by cancer. The most common risk factors include family history, smoking, and exposure to toxins. Inflammatory bowel disease (IBD) can also
increase cancer risk. But despite the increased risk, it is important to remember that most people with ulcerative colitis (UC) or Crohn's disease (CD) never develop cancer. This newsletter will focus
on IBD and colorectal cancer. It will also address lymphoma and small bowel adenocarcinoma, two other types of cancer that are sometimes associated with IBD.
Colorectal Cancer and IBD
What is colorectal cancer?
Normally, the cells in your body multiply in an orderly, controlled manner. This is necessary for healthy body function and to repair damaged tissue. In contrast, cancer is a disease marked by
uncontrolled cell growth. Cells reproduce when your body does not need them, resulting in a mass of cells called a tumor.
A tumor can be benign. That is, it usually grows slowly and does not spread to other parts of the body or invade and destroy nearby tissue. Benign tumors are usually harmless, but if the tumor is
big enough, its size and weight can pressure nearby blood vessels, nerves, or organs, or otherwise cause problems. The tumors we call cancer are malignant; that is, they are faster–growing and have the
ability to spread, invade, and destroy tissue. They are likely to grow uncontrollably and invade other parts of the body causing problems. In colorectal cancer, tumors typically arise from the cells
that line the colon (also known as the large intestine) and/or the rectum. Colorectal cancer is one of the most common forms of cancer. It is the second leading cause of cancer–related death in men and
women in the United States.
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How does colorectal cancer develop?
In patients without IBD, the mechanism and process of colorectal cancer is very well understood. The cells lining the colon grow into a benign fleshy growth called a polyp. The polyp either remains
benign or may continue to grow and to become cancerous, depending on its characteristics and the patient's genetic profile.
The natural history of colorectal cancer in patients with IBD is less well understood. One hypothesis is that the constant process of inflammation and repair that occurs in the gastrointestinal tract
may increase cancer susceptibility. For example, the cells lining the colon and/or rectum may divide so rapidly that mutations (that is, genetic mistakes) are more likely. These mutations become
precancerous (called dysplastic cells or dysplasia) and can later turn into cancer. Other theories suggest that cancer in IBD may be due to accumulation of cancer–promoting by–products of cell re–growth.
Although not yet proven, we believe that keeping the inflammation under good control will decrease one's risk of developing cancer.
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Are you at risk?
About 145,000 Americans are diagnosed with colorectal cancer each year, and IBD increases the risk of developing colorectal cancer by about two to five times the normal risk. However, it's important
to remember that, if detected early, colorectal cancer is one of the most treatable cancers, and survival rates in IBD patients are the same as the survival rates in the general population.
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If you have UC
UC affects the lining of your colon and/or rectum. If you have UC, there are two primary risk factors for developing colorectal cancer. The first is how long you have had the disease. Your
colorectal cancer risk does not begin to increase until approximately eight to ten years after UC onset. At that point, your risk begins to increase about 0.5% per year, until it reaches a risk
somewhere between 10% to 18%. (Eaden et al, 2001) The second risk factor is the extent to which your large bowel is affected. If only your rectum is inflamed, your cancer risk is most likely
similar to that of the general population; if only part of your colon is inflamed, you are at intermediate risk; and if your entire colon is inflamed, you are at greatest risk.
Other risk factors may include primary sclerosing cholangitis (a liver disease involving bile duct inflammation) (Lindberg et al, 2001), a family history of colorectal cancer
(Askling et al., 2001), and liver transplantation. New research also suggests that there may be two, potentially modifiable risk factors: backwash ileitis (reflux of colonic contents back into
the small intestine) (Heuschen et al., 2001) and inflammation severity (Itzkowitz and Yio, 2004).
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If you have Crohn's disease
CD can affect the lining of any part of your digestive system, from your mouth to your anus. If your colon is affected, your colorectal cancer risk is believed to be the same as if you had
UC (see above). Other risk factors related to CD are not as well understood. Researchers believe that if CD does not involve your colon, then your colorectal cancer risk is similar to that of
the general population. Therefore, it's important to know which part of the bowel is involved when you have Crohn's disease.
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How to reduce your risk?
The first step in reducing your colorectal cancer risk is to schedule an annual examination with your gastroenterologist, regardless of how healthy you feel (Eaden et al., 2000). The exam is a good
time to discuss concerns that you have and report any changes in your IBD symptoms. Symptoms like diarrhea and rectal bleeding may signal an IBD flare-up or rarely they may be early signs of colon cancer.
A colonoscopy may be necessary to investigate the source of your symptoms. In addition, even without symptoms, routine colonoscopy is recommended in order to identify the earliest pre-cancerous changes,
called dysplasia. Although polyps may develop in IBD-related colon cancer, it is known that dysplasia may occur in otherwise flat mucosa. Therefore, when a colonoscopy is performed for cancer detection
or prevention in IBD, the gastroenterologist will obtain random biopsies in addition to removing polyps.
There are two main types of polyps in IBD. Pseudopolyps are swollen, inflamed tissue and not precancerous. However, a recent study suggests that the presence of pseudopolyps may be associated with
an increase in colorectal cancer risk, possibly due to the fact that pseudopolyps reflect a colon that may have had a greater degree of inflammation (Velayos et al., 2006). A second type of polyp is
similar to the type of polyp that we see in non-IBD patients and contains the precancerous changes known as dysplasia.
Dysplasia is determined by examining polyps or biopsies under the microscope and is graded as "high-grade," "low-grade," or "indefinite." Both high-grade- and low-grade dysplasia are associated with
an increased risk of colon cancer, and new research suggests that there may also be an association between indefinite dysplasia and colon cancer. Therefore, if dysplasia is detected, your physician may
suggest a proctocoloectomy (i.e., surgical removal of your colon and rectum). In a recent study of patients who underwent surgery following dysplasia detection, cancer was found in 45.5% of those with
high grade dysplasia and in 20% of those with low grade dysplasia (Rutter et al., 2006). Surgery for IBD is briefly described in the newsletter titled
"The Clinical Course of IBD" by Dr. Abreu and will be discussed in more detail in a future newsletter.
To identify dysplasia during a colonoscopy, your doctor may take a biopsy (a painless tissue sample) from the lining of your colon. Your gastroenterologist will probably suggest that you schedule a
regular preventive colonoscopies every one to two years after you have had IBD for 8 or 10 years. An exception is the patient with the auto-immune liver inflammation known as PSC. Because of this risk,
colonoscopies start at the time of diagnosis.
In addition to regular colonoscopies, we believe that taking your IBD medication regularly may reduce the risk of colorectal cancer in IBD. Aminosalicylates (5-ASA drugs like mesalamine, balsalazide,
sulfasalazine, olsalazine), in particular, appear to have a positive effect on risk. For more information about IBD medication, see the newsletter titled
""Staying on Your Medication" by Dr. Hanauer. Although unproven, some physicians believe that folic acid supplements may
also help decrease colorectal cancer risk (Lashner et al., 1997).
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Small Bowel Adenocarcinoma, Lymphoma, and IBD
Two other types of cancer that are sometimes associated with IBD are small bowel adenocarcinoma and lymphoma. Because these cancers are extremely rare, the relationship of each to IBD is not as well
understood as the relationship between colorectal cancer and IBD.
Small bowel adenocarcinoma is very uncommon and accounts for only 1% to 5% of all malignancy in the gastrointestinal tract. If you have UC, you do not have an increased risk, since the small bowel is
not involved in UC. Only about 130 cases of small bowel adenocarcinoma in patients with CD have been reported in the world's medical literature (Kronberger et al., 2006). Small bowel adenocarcinoma risk
appears to be associated with having CD for more than 10 years (Palascak-Juif et al., 2005), but other risk factors for small bowel adenocarcinoma in CD are not well established. Some researchers think
that if CD affects the ileum (the final section of your small intestine), you are at increased risk of small bowel adenocarcinoma. Others think that risk may be related to gender (with males having
increased risk), age at disease onset (i.e., age less than 30 years), surgery in which loops of small bowel are bypassed, and the presence of chronic, active CD with stricture and fistulas. Trying to
keep your CD in remission is the best strategy for avoiding small bowel adenocarcinoma. Small bowel adenocarcinoma can be difficult to diagnose and is usually diagnosed when a patient has symptoms of
bowel obstruction and at the time of surgery.
The lymphatic system is part of our body's immune system which helps us to fight infections and when not controlled, is the cause of IBD. Lymphoma is a general term for a group of cancers that
originate in the lymphatic system. Lymphomas occur when a lymphocyte (a type of white blood cell) undergoes a malignant change and begins to multiply and eventually crowd out healthy cells. This process
usually begins in lymph nodes or collections of lymphatic tissue in organs like the stomach or intestines. In some cases, lymphomas involve the bone marrow and the blood, and may spread from one part of
the body to another. It is known that rarely patients with long-standing IBD may develop lymphoma. In addition, a recent analysis of six studies has suggested a four-fold increase in lymphoma risk for
IBD patients taking immunomodulators, like azathioprine or 6-MP. However, in the absence of a controlled clinical trial, it is impossible to determine whether the increased risk is related to the disease
severity, the medication, or a combination of the two. In another study, investigators determined that azathioprine would have to cause a greater than 9.8-fold increased risk of lymphoma for an
alternative treatment to be the preferred choice for treating IBD instead of azathioprine (Lewis et al., 2001).
It is important to remember that, while the risk of both small bowel adenocarcinoma and lymphoma are increased in patients with IBD, it is still very low relative to the high rate of clinical
improvement for IBD gained by using currently available medications.
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Summary
While most IBD patients never develop colorectal cancer, both UC and CD patients who have had IBD affecting the colon for at least 8 to 10 years may have an increased risk for colorectal cancer.
There are defined prevention strategies for colon cancer in IBD that include periodic colonoscopies and biopsies as well as persistent compliance with maintenance medications.
Small bowel adenocarcinoma in long standing Crohn's disease is extremely rare, and patients developing new symptoms of bowel obstruction should notify their physician. Although some investigators
think that the immunomodulator therapy used to control IBD may increase a risk of lymphoma, it remains unproven and it is believed that the benefit of such therapy outweighs that potential risk.
Contact your gastroenterologist to discuss risk factors specific to your situation and to determine the most appropriate preventive measures for you.
This information has been reviewed and approved by CCFA's National Scientific Advisory Committee.
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