Celiac Disease Is a Risk Factor for Mature T and NK Cell Lymphoma: A Mendelian Randomization Study

Abstract

Celiac disease (CeD) is an immune-mediated disorder triggered by gluten ingestion that damages the small intestine. Although CeD has been associated with a higher risk for cancer, the role of CeD as a risk factor for specific malignancies, such as enteropathy-associated T-cell lymphoma (EATL), remains controversial. Using two-sample Mendelian randomization (2SMR) methods and the summarized results of large genome-wide association studies from public repositories, we addressed the causal relationship between CeD and eight different malignancies. Eleven non-HLA SNPs were selected as instrumental variables (IVs), and causality estimates were obtained using four 2SMR methods: random-effects inverse variance-weighted, weighted median estimation, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO). We identified a significant causal relationship between CeD and mature T/NK cell lymphomas. Under a multivariate Mendelian randomization model, we observed that the causal effect of CeD was not dependent on other known lymphoma risk factors. We found that the most instrumental IV was located in the TAGAP locus, suggesting that aberrant T cell activation might be relevant in the T/NK cell malignization process. Our findings provide new insights into the connection between immune imbalance and the development of severe comorbidities, such as EATL, in patients with CeD.

The causality between gut microbiota and non-Hodgkin lymphoma: a two-sample bidirectional Mendelian randomization study

“…By conducting a meta-analysis of each Wald ratio of the included valid IVs, it can provide the most accurate estimate of the effect. This approach is also commonly seen in other literature (Legason et al, 2017;Lu et al, 2023;Martín-Masot et al, 2023;Ruan et al, 2023;Li et al, 2024;Zheng et al, 2024). The IVW method is divided into random-effects IVW and fixed-effects IVW, with the selection based on heterogeneity in MR results (Greco et al, 2015).…”

Optimizing Gluten Extraction Using Eco-friendly Imidazolium-Based Ionic Liquids: Exploring the Impact of Cation Side Chains and Anions

“…Around 0.5∼6% of people worldwide have celiac disease or nonceliac gluten sensitivity (NCGS). − Celiac disease and NCGS are food allergy diseases, and the reason comes from gluten-induced immune responses that attack the body. , Gluten allergy symptoms include bloating, chronic diarrhea, depression, anxiety, etc. It raises the risks of enteropathy-associated T-cell lymphoma, non-Hodgkin’s lymphoma, and adenocarcinoma of the small intestines when celiac patients do not control their gluten intake. − …”

“…It raises the risks of enteropathy-associated T-cell lymphoma, non-Hodgkin’s lymphoma, and adenocarcinoma of the small intestines when celiac patients do not control their gluten intake. 8 − 10 …”

Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet

“…The problem is that untreated celiacs or those whose diagnosis has been delayed, despite having no symptoms, may have an exacerbated and chronic activation of the immune system, which is uncontrolled for a longer time, leading to a worse prognosis, an accentuation of symptoms and the appearance of other autoimmune diseases such as type 1 diabetes or gluten-dependent hepatitis, which are frequent in CD patients [10,11]. Also, they may be affected by a variety of adverse consequences, some serious such as the development of malignant tumors [12]. Therefore, at the present time, the main challenge, like for other genetic-based diseases (such as some types of cancer and diabetes, among others), is to study in genetically predisposed individuals, on the one hand, which factors are involved in the development or not of CD and, on the other, to find biomarkers for its early diagnosis and follow-up.…”

“…The fact is that the GFD seems to play an important role in the pathogenesis of tumor development, since some studies have described a greater development of tumors the later the diagnosis is made and in patients who have not followed the GFD [16]. Thus, untreated CD is associated above all with T-cell lymphoma (EATL) [12] and small bowel adenocarcinoma [17], although a higher incidence of non-Hodgkin's lymphoma and colorectal cancer has also been described [18,19].…”