Sección de Gastroenterología y Nutrición Infantil, Hospital Regional Universitario de Málaga, 29011 Málaga, Spain.
Instituto de Nutrición y Tecnología de los Alimentos "José Mataix Verdú" (INYTA), Centro de Investigación Biomédica (CIBM), Universidad de Granada, 18016 Granada, Spain.
Int J Mol Sci. 2023 Apr 13;24(8):7216. doi: 10.3390/ijms24087216.
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 , 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.
乳糜泻（CeD）是一种由麸质摄入引发的免疫介导性疾病，可损害小肠。尽管 CeD 与更高的癌症风险相关，但 CeD 作为特定恶性肿瘤（如肠病相关 T 细胞淋巴瘤（EATL））的风险因素的作用仍存在争议。本研究使用两样本 Mendelian 随机化（2SMR）方法和来自公共存储库的大型全基因组关联研究的汇总结果，探讨了 CeD 与八种不同恶性肿瘤之间的因果关系。选择了 11 个非 HLA SNP 作为工具变量（IVs），并使用四种 2SMR 方法：随机效应逆方差加权、加权中位数估计、MR-Egger 回归和 MR 多效性残差和异常值（MR-PRESSO）来获得因果估计。本研究确定了 CeD 与成熟 T/NK 细胞淋巴瘤之间存在显著的因果关系。在多变量 Mendelian 随机化模型下，我们观察到 CeD 的因果效应不依赖于其他已知的淋巴瘤风险因素。我们发现最具工具性的 IV 位于，表明异常 T 细胞激活可能与 T/NK 细胞恶变过程有关。本研究结果为 CeD 患者免疫失衡与 EATL 等严重合并症发展之间的联系提供了新的见解。
