Celiac Disease Associated With Varying Risks for Cancers

Roughly 15% of hospitalized patients with have celiac disease (CeD) from a large cohort study had malignant neoplasms (MNs), especially small intestine, lymphoma, and skin cancers, according to results published in World Journal of Clinical Oncology.¹

“The study [emphasizes] the need for vigilant screening in CeD patients, particularly for specific malignancies like small intestine, lymphoma, and skin cancers,” the authors wrote. “These findings contribute to refining CeD management and understanding broader health care trends over 2 decades.”

Using National Inpatient Sample data from roughly 53,000 hospitalized patients living with CeD in the US between 2000 and 2019, researchers found positive associations with at least 16 distinct MNs: small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis.

The most significant increase was observed in cases of small intestinal adenocarcinomas, with an OR of 7.7, followed by lymphomas (OR, 2.06) and other malignancies affecting the gastrointestinal organs (OR, 2.01).

This study represents one of the largest studied cohorts of CeD, an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. | Image Credit: reineg-stock.adobe.com

Meanwhile, a reduced risk for respiratory and secondary malignancies was discovered. Some malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers.

Lymphomas had the highest prevalence of positive associations of malignancies with CeD. Small bowel carcinomas had the highest OR among the MNs, which showed a positive correlation with CeD, according to the study.

Mean differences in hospital stay (0.21 days) and total cost of care ($3172) were higher among the patients with CeD who also had MNs compared with patients with MNs but without CeD. But inpatient mortality was lower in CeD with MNs than non-CeD with MNs (0.72).

This study represents one of the largest studied cohorts of CeD, an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. The researchers used propensity score matching based on age, sex, race, and calendar year to compare patients with a primary or secondary diagnosis of CeD with patients who did not have CeD.

The CeD cohort with MN had a mean age of 68 years, 36% were male patients, and 84% reported a Caucasian race. By contrast, for the patients with CeD without MNs, the mean age was 53 years, 28% were male, and 79% reported a Caucasian race. African Americans patients comprised 1.9% of the CeD-with-MNs cohort and 2.96% of the CeD-without-MNs cohort.

The risk of MN development is higher in the early stages following a diagnosis of CeD, but the standardized incidence ratio (SIR) for MNs tends to decrease and may become statistically nonsignificant after the initial year of diagnosis or in subsequent years, the authors stated.

Worldwide, an estimated 1.4% of people have CeD based on serological markers and 0.7% based on histological data. CeD is unique because patients can halt the disease and even reverse mucosal damage by avoiding gluten.

The most common disorders associated with celiac disease are thyroid disease and type 1 diabetes, according to the Celiac Disease Foundation.² The later the age of diagnosis, the greater the chance of developing another autoimmune disorder, with a 10.5% chance for children aged 2 to 4 years, and a 34% for those older than 20 years.

“The precise pathogenic mechanism underlying malignancy development in CeD remains an enigma. Several factors, including but not limited to persistent inflammation, the release of proinflammatory cytokines, continual antigen stimulation, cytokine surges, heightened susceptibility to carcinogens, and nutritional deficiencies induced by the disease or the adoption of a gluten-free diet, have all been proposed as potential contributors to the onset of malignancies,” the authors wrote.

References

1. Haider MB, Sbihi AA, Reddy SN, Green P. Prevalence of malignant neoplasms in celiac disease patients - a nationwide United States population-based study. World J Clin Oncol. 2024;15(8):1048-1060. doi:10.5306/wjco.v15.i8.1048

2. Autoimmune disorders. Celiac Disease Foundation. February 2013. Accessed August 31, 2024. https://celiac.org/about-celiac-disease/related-conditions/autoimmune-disorders/