Celiac Disease and Cancer: What’s the Real Risk?

It sounds like two scenes from the same science fiction thriller. With celiac disease, the body’s immune system attacks its own gut lining. With cancer, cells grow abnormally and invade other parts of the body.

But real science indicates people with celiac disease face increased risk for certain types of cancer. Fortunately they’re rare forms, and the risk declines when the gut lining heals.

“One [cancer] is called enteropathy-associated T-cell lymphoma. It’s a kind of lymphoma of the small intestine,” says Benjamin Lebwohl, M.D., assistant professor of medicine in epidemiology at the Celiac Disease Center at Columbia University in New York City. Another is small intestinal cancer, or small intestinal adenocarcinoma. These cancers are not seen very often in the general population but occur at an increased rate in people with celiac disease.

“These findings underscore the fact that celiac disease and the intestinal inflammation that is involved in this condition are a health hazard,” Lebwohl says. “The evidence is very good that healing in the intestines reduces the excess risk [for cancer], and there’s also evidence that following a gluten free-diet leads to healing of the intestines.”

It’s one more argument for why people with symptoms or risk factors should be tested for celiac disease and, if diagnosed, stick to a strict gluten-free diet.

Haunted by memory

Ken Kilgore, Ph.D., director of partnered pharmacology at Janssen Pharmaceutical Companies of Johnson & Johnson in Pennsylvania, has an especially good reason not to cheat.

“It doesn’t honor my dad,” Kilgore explains. “He was my greatest friend in the world, and that just taints the sacrifice he made if I go and cheat.”

In 2002 Kilgore’s father, Donald, had been suffering from severe weight loss when in September he was diagnosed with B-cell lymphoma. Despite chemotherapy his condition continued to decline. He could no longer pursue his passions for golfing or watching University of Michigan football with his son.

“We had season tickets for decades, and football Saturdays were a much-loved fixture of our family,” Ken Kilgore recalls. “However it became clear mid-way through the 2002 season that he was not strong enough to continue going to games. He and I had watched Michigan football together for 35 years and rarely missed a game until then.”

At the time, Ken Kilgore was an adjunct professor at University of Michigan Medical School, Ann Arbor. A gastroenterologist friend there suggested his father should get tested for celiac disease. The results came back positive.

In hindsight, Ken Kilgore believes his father’s celiac disease had been active for at least 10 years before the cancer diagnosis. Donald Kilgore had some nutritional problems, particularly low levels of vitamin B12.

Recent research shows increased cancer risk declines when celiac disease is diagnosed and treated effectively, a fact that still haunts Ken Kilgore. “We were definitely in the Dark Ages of celiac awareness,” he says.

Ken Kilgore had his father switch care to University of Michigan Medical Center because he thought physicians there were among the few who were up-to-date on celiac disease. “Unfortunately it was too late by that point,” he laments.

While getting tested for celiac disease, Donald Kilgore underwent an upper digestive tract endoscopy that revealed the cancer was actually T-cell lymphoma. For half a year his treatment had targeted the wrong form of cancer. It was too late to start over. Donald Kilgore died in September 2003, at the age of 67.

After Donald Kilgore was diagnosed, the whole family got tested for celiac disease. Ken Kilgore was the first to test positive in 2003, followed by his daughter, who also has Down syndrome, his nephew and, most surprisingly, his mother.

“We look for hidden blessings in this whole adventure,” says Ken Kilgore, now 50. “We feel in the long run that my dad did something great for all of us.”

Understanding the risk

Alice Bast, president and CEO of Beyond Celiac, a patient advocacy organization based in Pennsylvania, says people diagnosed with celiac disease are concerned about associated health problems, including cancer.

“In fact, in a recent survey that we will be submitting for publication later this year, more than 80 percent of adults in our community are specifically worried about their increased cancer risk,” she adds.

The risk came to light only recently. One of the first studies to suggest a link appeared in American Journal of Medicine (2003); it reviewed statistics from 381 celiac disease patients seen between 1981 and 2000 at New York-Presbyterian Hospital.

Researchers found a higher-than-expected incidence of non-Hodgkin lymphoma, cancer of the small bowel, esophageal cancer and melanoma in this group. B-cell lymphoma and enteropathy-associated T-cell lymphoma are two types of non-Hodgkin lymphoma. No elevated risk was found for colon, lung or breast cancer.

However, before raising alarm, Lebwohl points to weaknesses in this data.

The study was performed at a major referral center for celiac disease, he notes. There’s always concern that studies coming out of such settings don’t apply to celiac disease patients in general.

“Patients who come to our center might be different in important ways. They might be referred to our center because of particularly complex problems or difficult-to-manage disease. Their risk might be different from the typical celiac disease patient,” Lebwohl explains.

“Some of the confusion derives from the fact that cancer is often lumped into one outcome when cancer represents many different kinds of disease,” he continues. “In fact celiac disease might increase the risk of one cancer and decrease the risk of another. Studying them on the aggregate often leads to confusion. It’s important to evaluate each cancer with regard to its relationship with celiac disease.”

Early findings provoked a variety of further research. Several studies from Scandinavia have provided clarity. They’re important, Lebwohl says, because they’re population-based.

In other words they include essentially all celiac disease patients from a large population, rather than a few under special circumstances.

“In general studies coming out of population-based settings show lower risks and diminished increases of risk,” Lebwohl observes.

For example a 2014 study from University of Tampere, Finland, analyzed data on 32,439 celiac disease patients between 2002 and 2011. It is the largest study of its kind completed to date. It confirmed an increased risk for non-Hodgkin lymphoma and small intestinal cancer, though the rates were lower than in other studies.

“Patients should be aware that while the risk of these cancers is increased compared to the general population, the absolute risk is modest in size,” Lebwohl points out. For example one study found that over the course of 10 years, less than 1 percent of patients with celiac disease developed lymphoma.

That means it’s rare even for people with celiac disease.

Not all cancers ARE the same

The Finnish study didn’t support evidence for a link between other cancers and celiac disease. Overall scientific findings have been ambiguous on esophageal cancer, melanoma and colon cancer.

However the Finnish study also provided some good news. The overall risk of cancer for newly diagnosed celiac disease patients was no higher than for the general population.

“There are a couple of cancers that appear to be less common in patients with celiac disease,” explains Lebwohl. “Lung cancer and breast cancer are the two that have been studied most. For some reason celiac disease appears to be protective against these cancers.”

One possible reason is that research has shown celiac disease patients are less likely to be smokers. But even with smoking habits removed from the equation, celiac disease appears to protect against lung cancer, Lebwohl says.

Similarly celiac disease patients may have less body fat, which could reduce the risk for breast cancer. Also some studies have shown that women with celiac disease “have later onset of menstruation and earlier onset of menopause compared to the general population,” Lebwohl explains. “It could be that these hormonal factors are influencing breast cancer risk.”

While these protections remain a puzzle, Lebwohl says he is most interested in research “honing in on lymphomas,” because these cancers seem to be the ones celiac disease tracks with most closely.

“It makes a sort of logical sense that patients with celiac disease who have inflammation in their small intestine would have cancers in their small intestine,” he points out, but research has not yet proven a cause-and-effect relationship.

The link with cancer helped scientists realize celiac disease is not only an intestinal condition but rather an autoimmune disorder, he adds.

Call for prevention

Because non-Hodgkin lymphoma and cancer of the small intestine are rare even in celiac disease patients, the risk calls for vigilance more than alarm.

“With cancer, early diagnosis is key,” Bast says. “Those diagnosed with celiac disease should also be monitored annually by their physician.” The Beyond Celiac website identifies the tests patients should receive yearly.

Lebwohl says screening for preventable cancers should be the same for those with celiac disease as for the general public, including colonoscopy and mammography at the appropriate ages.

Ken Kilgore (top left) and his father Donald (top middle) with their family

“As for additional screening measures, none are routinely advised,” he says. “But patients with celiac disease should have regular medical follow ups because of the association with these cancers, including lymphoma.” This will help with early detection of any complications requiring investigation for cancer.

Given the evidence that treating celiac disease can reduce the risk of lymphoma, a follow-up biopsy might provide “important prognostic information,” he adds. A study of Swedish patients who underwent a second biopsy at an interval after starting the gluten-free diet showed the relationship between intestinal healing and risk of lymphoma.

“We compared those whose intestines had healed to those whose intestines failed to heal. Those who had healed no longer had an increased risk of lymphoma” Lebwohl says. This raises concern for celiac disease patients who do not heal despite following a strict gluten-free diet.

“These are the patients who we like to follow the closest,” Lebwohl says. “This is a substantial proportion of patients, some of whom have persistent symptoms but others [who] actually feel quite well,” despite poor healing.

Patients who have persistent intestinal damage meet with the celiac center’s dietitian more frequently than those who heal. “We try to drill down ways in which they might be exposed to gluten unintentionally,” Lebwohl explains. “This is a population that might benefit from [drug] therapy, if such therapy were to be developed in the future.”

But the absolute risk even for these patients is low.

“Those with persistent abnormalities on their intestinal biopsy have an increased risk compared to those who heal, but it’s still only about 1 percent risk of lymphoma over the course of 10 years,” Lebwohl says. “The risk should be treated the way other risk factors are generally treated, for an example having high cholesterol.”

Lurking feeling

Still Bast says cancer is a common concern for people with celiac disease, particularly those with family members who have been diagnosed with lymphoma or cancers of the gastrointestinal tract, blood, thyroid or pancreas.

“For many of us there’s always that lurking feeling that these instances may be connected to celiac disease,” she says. “My own mom died from pancreatic cancer at the age of 52. There’s no way to know for sure, but looking back, I think she had undiagnosed celiac disease. Many of us have stories like this.”

Patients with a family history of cancer are often concerned that it will increase their personal risk, Lebwohl says. In some cancers this is true; for example colon cancer. However family history doesn’t appear to increase the risk for lymphoma in celiac disease.

The lack of a genetic link only emphasizes the importance of effective, timely treatment for people with celiac disease.

“Celiac disease disrupts and devastates lives,” Bast says, but the recognition of increased cancer risk makes it “undeniable that celiac disease is serious and needs research for a cure.” She also points out an estimated 83 percent of people with celiac disease remain undiagnosed. “Their increased health risks are unrecognized and unmonitored by their healthcare professionals. It doesn’t get more serious than an increased cancer risk,” Bast says.

She encourages anyone diagnosed with celiac disease to talk to their relatives and encourage them to get tested. “We’ve found that once educated on the long-term health risks of undiagnosed and untreated celiac disease, people are more likely to get tested,” she notes.

Ken Kilgore looks back at the impact undiagnosed celiac disease had on his family.

“Celiac-associated cancer takes things, even beloved things, away long before one actually passes away. Within a few months of his diagnosis, my dad was unable to do the things he loved. [T-cell lymphoma] is a totally unforgiving and merciless disease,” he says. “It is also preventable.

“This last point is what haunts me the most. All the signs of celiac disease were there long before he got cancer, and we missed it. It is the survivors like me who have to carry that burden for the rest of our lives.”

He says he hasn’t watched a University of Michigan game since his father died. GF

Van Waffle is research editor for Gluten-Free Living. He blogs about nature, gardening and local food at vanwaffle.com.