Gluten-Free Diet May Reduce Cancer Risk in Celiac Disease

September 14, 2021 — The overall risk of cancer increases slightly in patients over 40 years of age during the first year after being diagnosed with celiac disease, but the risk decreases during the year after diagnosis, a Swedish study of 47,000 people with celiac disease shows. “Celiac disease is associated with an increased risk of various cancers, and we believe this is due to long-term inflammation caused by gluten,” says study author Benjamin Lebwal, MD, director of clinical research on celiac disease at Columbia University. Center in New York.

I write in a magazine Clinical Gastroenterology and HepatologyThe authors explain that most studies looking at the risk of cancer in celiac patients were conducted before the widespread use of serological testing for celiac disease and access to gluten-free foods became widely available. Earlier studies have linked celiac disease to gastrointestinal malignancies such as small bowel adenocarcinoma and lymphomas.

A preliminary analysis of this Swedish cohort showed that the risk of small bowel adenocarcinoma, although low, persisted up to 10 years after the diagnosis of celiac disease. In a study published in GastroenterologyThe authors found that the risk of developing adenocarcinoma and small bowel adenoma was significantly higher in people with celiac disease compared to people without the disease.

“We knew from previous research that people with celiac disease are at an increased risk of developing certain types of cancer, but there has been limited research into this risk with celiac disease in the 21st century, where there is greater acceptance (leading to faster diagnosis) and increased access to gluten-free foods (which may provide more effective treatment),” says Lebwohl, who is also director of quality improvement in the Division of Digestive and Liver Diseases at Columbia University. “We sought to determine if there is an increased risk of cancer in the modern era, and we found that the increased risk still exists, but that the increase is small and decreases after the first year after the celiac disease is diagnosed. “

This nationwide cohort study in Sweden included 47,241 patients with celiac disease (62% women; mean age 24 years), of whom 64% had been diagnosed since 2000. Each patient was matched for age and gender with five controls. After a median follow-up of 11.5 years, patients with celiac disease were found to have a 1.11-fold increased risk of developing cancer overall compared to controls. The corresponding cancer rates were 6.5 and 5.7 per 1000 person-years, and most of the excess risk was due to gastrointestinal and hematologic cancers.

The overall risk of developing cancer increased in the first year after the diagnosis of celiac disease, but not after.

“It appears that the increased risk of cancer in people with celiac disease has decreased over time, and this may be due to the long-term beneficial effects of a gluten-free diet,” says Lebwohl.

The authors suggest that the risk of developing cancer, followed by a decrease to no risk at all, may be associated with increased monitoring and medical examinations of patients with celiac disease. Also,

The authors write that symptoms of cancer, such as weight loss, could lead to widespread testing that detects celiac disease.

For cancer subtypes, the strongest association between celiac disease and cancer was found for hematologic, lymphoproliferative, and gastrointestinal cancers. Among gastrointestinal cancer subtypes, an increased risk was found for hepatobiliary and pancreatic cancers but not for gastric or colorectal cancers. The risk of cancer with celiac disease decreased in breast and lung cancers, which the authors suggest may be due to lower body mass index and smoking rates, respectively, seen in people with celiac disease.

Some types of cancer persist after 1 year.

Although there was no overall risk of developing cancer for more than 1 year after the diagnosis of celiac disease, the risk of hematologic and lymphoproliferative cancers remained. While the cumulative increased risk of gastrointestinal cancer was not significantly more than 1 year after the diagnosis of celiac disease, the risk of hepatobiliary cancer and pancreatic cancer persisted.

“We found that the risk of gastrointestinal cancer is increased in people with celiac disease compared to the general population, but these risks vary depending on the type of cancer,” Lebwohl says. “For example, the risk of pancreatic cancer is increased in people with celiac disease compared to the general population, while the risk of colon cancer in people with celiac disease is not increased compared to the general population.

“But pancreatic cancer is much less common than colon cancer. We found that pancreatic cancer occurs in 1 in 5,000 people with celiac disease per year, while colorectal cancer occurs in 1 in 1,400 people per year. Cancer was about 1 in 700 a year among people with celiac disease,” says Lebwohl.

The overall risk of cancer was highest in patients diagnosed with celiac disease after age 60 and did not increase in those diagnosed with celiac disease before age 40. The authors note that in recent years there has been a marked increase in the diagnosis of celiac disease in people over 60 years of age, an age group with a higher risk of developing severe outcomes associated with refractory celiac disease. The risk of cancer was similar among patients diagnosed with celiac disease before or after 2000.

Because this is an observational study, a causal relationship cannot be proven, and the authors suggested that the results may not be applicable to settings outside of Sweden’s relatively homogeneous ethnic population.

Carol E. Semrad, MD, professor of medicine and director of clinical research at the Celiac Disease Center at the University of Chicago Medical University, says, “This is an observational study and therefore cannot answer whether celiac disease is a cause of cancer or just an association.” She adds that “It is not known why the risk of certain types of cancer is higher in celiac disease.

“This article argues against late diagnosis and low detection rates to explain the increase in cancer risk, since those diagnosed with celiac disease before 2000 had the same cancer risk as people diagnosed after 2000 on diagnostic testing. Earlier diagnosis and access to gluten. The free diet was better,” says Semrad.

Link to mortality data

The authors say that the increased cancer risk, limited to the first year after diagnosis, is consistent with previous studies of celiac disease incidence and mortality.

Research published in 2019 in United European Gastroenterology studied the risk of mortality in 602 patients with celiac disease from Lothian, Scotland, diagnosed between 1979 and 1983.

They were observed from 1970 to 2016. Mortality from all causes was 43% higher than in the general population, mainly from hematological malignancies, and this risk was highest during the first few years after diagnosis.

Analysis of causal mortality in the Swedish cohort published in 2020 JAMAfound that celiac disease is associated with a small but statistically significant increased risk of mortality. After a median follow-up of 49,829 patients with celiac disease over 12.5 years, the mortality rate was 9.7 and 8.6 deaths per 1,000 person-years compared to the general population, respectively. People with celiac disease were at increased risk of dying from cancer, cardiovascular disease, and respiratory disease. The overall risk of mortality was highest during the first year after diagnosis of celiac disease, after which the risk decreased with the transition to a gluten-free diet but remained moderately elevated in the long term.

However, a Finnish population study published in the American Journal of Gastroenterology found no increase in overall mortality in patients with celiac disease. The study included 12,803 adults diagnosed with celiac disease between 2005 and 2014. Participants were followed up for a median of 7.7 years, and mortality from all malignancies, gastrointestinal malignancies, or cardiovascular disease did not increase among patients with celiac disease compared to overall rates. Population. Mortality from lymphoproliferative diseases was higher in patients with celiac disease but lower than previously reported.

Lebwall and colleagues note that the incidence of cancer types varies by age and geographic region of the study population, as does the diagnosis of celiac disease, which may explain why increased cancer risk or cancer-related mortality in patients with celiac disease has not always been reported.

Ludwigsson is coordinating the study on behalf of the Swedish quality registry IBD. This study received funding from Janssen. The rest of the authors found no conflicts.

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