Celiac Disease Is a Risk Factor for Mature T and NK Cell Lymphoma: A Mendelian Randomization Study
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AuthorMartín Masot, Rafael; Carmona López, Francisco David; Nestares, Teresa; Bossini Castillo, Lara María
Celiac diseaseT-cell lymphomaPolymorphismsRisk factorMendelian randomization
Martín-Masot, R.; Herrador-López, M.; Navas-López, V.M.; Carmona, F.D.; Nestares, T.; Bossini-Castillo, L. Celiac Disease Is a Risk Factor for Mature T and NK Cell Lymphoma: A Mendelian Randomization Study. Int. J. Mol. Sci. 2023, 24, 7216. [https://doi.org/10.3390/ijms24087216]
SponsorshipMinistry of Science and Innovation, Spain (MICINN) IJC2018-038026-I; European Commission; Spanish Ministry of Science and Innovation through the Spanish National Plan for Scientific and Technical Research and Innovation PY20_00212; Andalusian Government B-CTS-584-UGR20 B-AGR-658; FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades; Grant "Investigation grant program by the Association of Celiacs and Sensitive to Gluten of the Community of Madrid" PID2020-120157RB-I00
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.