Inflammatory Bowel Disease and Cancer Risk
by Sharon Reynolds, medically reviewed by Dr. C.H. Weaver M.D. 2/2020
"Better screening and modern IBD treatments are improving the odds."
A woman newly diagnosed with inflammatory bowel disease (IBD) will likely go home and immediately type those words into a search engine. Along with information on its causes and treatment, she may encounter what seems like a frightening fact: that the disease brings with it an increased risk of some types of cancer.
For people with IBD, cancer risk “is very much on their radar. It’s one of the things patients fear most, probably only second to the fear of having a permanent ostomy,” says David Rubin MD, co-director of the Digestive Diseases Center at the University of Chicago.
But the good news, adds Dr. Rubin, is that this fear is out of proportion to the actual likelihood that a patient with IBD will develop cancer. And with modern IBD treatments and screening technologies to catch some cancer types early, at a precancerous stage, the risk is now dropping.(1)
An Inflammatory Environment
With IBD the immune system in the gut is overactive and damages normal tissues.* There are two types of IBD: Crohn’s disease and ulcerative colitis. With Crohn’s disease damaging inflammation can occur anywhere along the lining of the digestive tract, from the mouth to the anus. With ulcerative colitis it is mostly confined to the colon and rectum.(2)
The resulting chronic inflammation can damage the lining of the digestive tract, sometimes severely, leading to the pain, bloating, bowel problems, and bleeding associated with IBD. It can also increase a patient’s risk of cancer through many mechanisms, such as damaging cells’ genetic material and increasing the levels of certain molecules that promote tumor growth.(3,4)
As one might expect, people with ulcerative colitis or with Crohn’s disease that involves the colon or rectum have an increased risk of colorectal cancer—almost six times higher than people without IBD.
Fortunately, regular screening colonoscopies greatly reduce this risk. “The goal for the prevention of colorectal cancer in patients with IBD, like those without IBD, is to detect it before it gives you symptoms—to find precancerous lesions so that we can intervene [early],” says Dr. Rubin.
In the past this search was complicated by the unusual nature of precancerous growths in people with IBD, explains Dr. Rubin. In people who do not have chronic inflammation in the colon, precancerous growths usually come in the form of polyps; these are small, mushroom-shaped growths protruding from the lining of the intestine, easily seen—and removed—with the endoscopes used for colonoscopy.
But in people with IBD, precancerous growths are often flat lesions that can be hard to distinguish from the intestinal lining. Chronic inflammation can in turn make it more difficult to see these flat lesions.
“Older technologies we had to look at the colon were unable to see most of these lesions,” says Dr. Rubin. “But the field has advanced now, thankfully. We have better technology…and we can see much more than we used to be able to.” This technology includes high-definition digital imaging for endoscopes and contrast dyes that can hide blood vessels and highlight flat precancers.(5)
Better technology for monitoring precancers has led to a total rethinking of how to manage them, explains Dr. Rubin. In the past doctors would likely remove the entire colon if a precancer was found, for fear that other lesions could be hiding out of sight. “But if you can see the precancerous changes and remove them with the scope, you have the opportunity to follow those patients rather than send them all to surgery and have them lose their colons.” An international consensus statement recommends this more conservative approach.(6)
In conversations with her patients, Sunanda Kane, MD, MSPH, an IBD specialist at Mayo Clinic Rochester, emphasizes that their increased risk of colorectal cancer is manageable: “Even though you’re at greater risk for colon cancer, there are preventive measures, and they’re very effective.” She also reminds her patients that other ways to reduce the risk of colorectal cancer—like quitting smoking—are completely under their control.
Immunosuppressive Treatment: More Benefits Than Risks
Since 1998 the field of IBD treatment has been revolutionized by the introduction of so-called biologic drugs—drugs designed in the laboratory to attack specific proteins that play a role in disease. Several biologic drugs now approved to treat IBD, including Remicade® (infliximab) and Humira® (adalimumab), target proteins that ramp up the inflammation process.
For many patients these drugs can tamp down inflammation to the point where the lining of the gut has a chance to heal. This can greatly reduce the risk of gastrointestinal cancers.
“The degree of inflammation over time is the single largest independent risk factor for developing precancer or cancer. And the reason that’s an important message for people to understand is the implication—that your disease should be under excellent control to reduce your [cancer] risk,” says Dr. Rubin.
Many patients with IBD, however, come to the clinic having heard that drugs used to treat the disease increase the risk of cancer themselves, making some people reluctant to try effective therapies.
It is true that the immune system can play a role in killing off cancer cells before they grow into full-fledged tumors. Therefore long-term immunosuppression can slightly increase the risk of some cancer types, mainly skin cancer and lymphoma, in people with IBD.7 However, says Dr. Kane, the risk calculations are still firmly in favor of immunosuppressive treatment.
For example, she explains, people with IBD taking immunosuppressive therapies have a fourfold increased risk of lymphoma. She tells her patients that “in the U.S. the [average] risk of developing lymphoma is one in 10,000; so you multiply that by four, and you get four in 10,000. It’s still very unlikely. And the chance of your getting better on the therapy I’m going to give you is 70 percent. So, seven out of 10 people are going to get better, while only four out of 10,000 are going to get a cancer. There’s way more benefit than there is risk,” she asserts.
When biologic drugs for autoimmune diseases targeting a protein called tumor necrosis factor (TNF) first came on the market, researchers expressed concern that they might increase the risk of some solid tumors—and this made it onto the labels of these drugs. But follow-up studies have since minimized this concern.(8)
“There is no increased risk of solid tumors with anti-TNF therapy,” says Dr. Rubin. “It has been completely disproven in huge numbers of patients and long-term follow-up. But it’s a very common [belief], and it’s misunderstood. Much of the risk initially prescribed to anti-TNF drugs has since been shown to be caused by a much older class of immunosuppressive drugs, called thiopurines, which are not widely used anymore.(7,8)
“It doesn’t appear that being on [modern] therapy drives cancer risk higher,” adds Dr. Kane. “If anything, therapy decreases your risk because it puts the inflammation under control.”
But Dr. Rubin always reminds his patients who have the disease well under control not to get complacent about cancer screening. “You’re not off the hook,” he says. “Unfortunately, when we finally see cancers in some of these people, a lot of times it’s because they were doing so well that they forgot they even needed [screening] done, and nobody was recommending it.”
Knowing What to Ask For
Sara Ringer has been living with a diagnosis of Crohn’s disease since she was 13, though she likely had the condition since birth. “I was in and out of the hospital since I was a baby, but we couldn’t figure out what was wrong until I was 13,” she recalls.
Two years ago, when she was 32, she got two new diagnoses: precancer of the cervix and several precancerous spots on her skin. Her doctor did mention that her skin precancers may have been due to immunosuppressive treatment. But with her gynecologist who found the cervical precancer, “No conversations took place that ‘this could have happened because you have IBD,’” says Sara.
She found out through her own research that cervical cancer risk may be elevated in women with IBD.(9) This is also thought to be due to immunosuppression, which makes it harder for the body to fight off infection with human papillomavirus (HPV), the cause of almost all cases of cervical cancer, explains Dr. Rubin. The good news, he adds, is that “this is now considered preventable” with available vaccines against HPV."
Awareness of risk for cancers outside the colon isn’t very common in people with IBD—or even their doctors—says Sara, who volunteers as a patient advocate for the Crohn’s & Colitis Foundation of America and blogs at inflamed-and-untamed.com.
“It’s pretty common to know that risk of colorectal cancer increases, but for others I think there’s a low awareness,” says Sara. “The unfortunate thing is that a lot of patients who have IBD don’t see an IBD specialist—they just have GI doctors, who aren’t as trained as IBD specialists. They may not have time to communicate those risks or even know about them themselves,” she adds.
Sara recommends that women with IBD make sure they ask for all the standard cancer screening tests available to them and to monitor things they can see on their own, such as suspicious moles and skin spots. “If their doctor doesn’t bring it up, they should advocate for themselves,” she concludes.
- For general information about IBD, see “IBD: Fighting a Fire Within” in Women Magazine, available at awomanshealth.com/ibd-fighting-a-fire-within.
Not All Screening Methods Work
Some methods used to screen for colorectal cancer in the general population are not appropriate for people with IBD, explains Dr. Rubin. These include CT colonography, also known as virtual colonoscopy, which does a poor job of finding flat precancers. Tests that look for blood in the stool as a sign of early cancer also won’t work because patients with IBD may have blood in their stool due to inflammation.
Rare Gastrointestinal Cancers
People with IBD have an elevated risk of other cancers of the gastrointestinal tract:
- Small bowel cancer
- Intestinal lymphoma
- Anal cancer
- Bile duct cancer
The amount of increased risk of these cancers can look terrifying out of context. For example, small bowel cancer is almost 30 times as likely to occur in someone with IBD as in the general population; however, reminds Dr. Kane, these cancers are very rare to begin with. “Thirty times rare is still rare,” she says.
Ulcerative Colitis Linked with Worse Colorectal Cancer Prognosis
According to the results of a study conducted in Denmark, colorectal cancer patients with ulcerative colitis have a worse prognosis than colorectal cancer patients without ulcerative colitis. These results were published in The American Journal of Gastroenterology.
Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. The disease develops in the large intestine, which includes the colon (the longest part of the large intestine) and the rectum (the last several inches).
Ulcerative colitis is a type of inflammatory bowel disease. It is characterized by inflammation of the lining of the colon and rectum. Ulcerative colitis is known to increase the risk of developing colorectal cancer, but it is uncertain whether it affects the prognosis of colorectal cancer.
To evaluate the effect of ulcerative colitis on colorectal cancer prognosis, researchers in Denmark conducted a study among 279 colorectal cancer patients with ulcerative colitis and 71,259 colorectal cancer patients without ulcerative colitis.
- Average age at colorectal cancer diagnosis was 62.6 years among patients with ulcerative colitis and 71.2 years among patients without ulcerative colitis.
- Colorectal cancer stage was similar in the two groups. Among patients with ulcerative colitis, cancer was localized in 46.6%, regional in 30.1%, and distant in 16.5%. Among patients without ulcerative colitis, cancer was localized in 44.0%, regional in 28.3%, and distant in 19.4%.
- After the first year of follow-up, risk of death was 24% higher in patients with ulcerative colitis than in patients without ulcerative colitis.
- After five years of follow-up, risk of death was 17% higher in patients with ulcerative colitis than in patients without ulcerative colitis.
The researchers conclude that although stage at colorectal cancer diagnosis is similar for patients with and without ulcerative colitis, colorectal cancer patients with ulcerative colitis appear to have worse survival. (10)
- Chapman CG, Rubin DT. The potential for medical therapy to reduce the risk of colorectal cancer and optimize surveillance in inflammatory bowel disease. Gastrointestinal Endoscopy Clinics of North America, 2014;24(3):353-65. doi: 10.1016/j.giec.2014.03.008.
- Fakhoury M, Negrulj R, Mooranian A, Al-Salami H. Inflammatory bowel disease: Clinical aspects and treatments. Journal of Inflammation Research. 2014;7:113-20. doi: 10.2147/JIR.S65979.
- Axelrad JE, Lichtiger S, Yajnik V. Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment. World Journal of Gastroenterology. 2016;22(20):4794-801. doi: 10.3748/wjg.v22.i20.4794.
- Beyaert R, Beaugerie L, Van Assche G, et al. Cancer risk in immune-mediated inflammatory diseases (IMID). Molecular Cancer. 2013;12(1):98. doi: 10.1186/1476-4598-12-98.
- Bae SI, Kim YS. Colon cancer screening and surveillance in inflammatory bowel disease. Clinical Endoscopy. 2014;47(6):509-15. doi: 10.5946/ce.2014.47.6.509.
- Laine L, Kaltenbach T, Barkun A, et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. 2015;148(3):639-51.e28. doi: 10.1053/j.gastro.2015.01.031.
- Dulai PS, Siegel CA. The risk of malignancy associated with the use of biological agents in patients with inflammatory bowel disease. Gastroenterology Clinics of North America. 2014;43(3):525-41. doi: 10.1016/j.gtc.2014.05.010.
- Williams CJM, Peyrin-Biroulet L, Ford AC. Systematic review with meta-analysis: Malignancies with anti-tumour necrosis factor-α therapy in inflammatory bowel disease. Alimentary Pharmacology and Therapeutics. 2014;39(5):447-58. doi: 10.1111/apt.12624.
- Rungoe C, Simonsen J, Riis L, Frisch M, Langholz E, Jess T. Inflammatory bowel disease and cervical neoplasia: A population-based nationwide cohort study. Clinical Gastroenterology and Hepatology. 2015;13(4):693-700.e1. doi: 10.1016/j.cgh.2014.07.036.
- Jensen AB, Larsen M, Gislum M et al. Survival After Colorectal Cancer in Patients with Ulcerative Colitis: A Nationwide Population-Based Danish Study. The American Journal of Gastroenterology. 2006;101:1-5.
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