Zhao Yang, Shao Yifan, Zhou Jing, Pei Jianing, Chong Jinchen, Lu Changye, Chen Yugen
The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China.
Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, PR China.
Sci Rep. 2025 Jan 8;15(1):1369. doi: 10.1038/s41598-025-85249-y.
Inflammatory bowel disease (IBD) is a multisystem condition that could affect the cutaneous systems, namely cutaneous extraintestinal manifestations (EIMs). It has been suggested that IBD is associated with erythema nodosum (EN), malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, the potential causal relationship between IBD and the mentioned above cutaneous EIMs is still unclear. This study aims to determine the effect of IBD on EN, MM and NMSC within a Mendelian randomization (MR) design. Summary-level data for IBD, EN, MM, NMSC were obtained from large-scale genome-wide association studies. We utilized five different methods, including the inverse variance weighted model (IVW), MR Egger, Weighted median, Simple mode, Weighted mode in the MR analysis, then the Cochran's Q test, the MR-Egger pleiotropy test, the MR-PRESSO global pleiotropy test and leave-one-out sensitivity test were used to evaluate the heterogeneity and pleiotropy of identified IVs. To further ensure the validity of our findings, we evaluated the strength of the instrumental variables using the F-statistic and estimated the statistical power of our study. Findings were verified using an independent validation dataset, as well as through different MR methods with different model assumptions. MR analysis suggested that genetically determined IBD had a detrimental causal effect on NMSC (IVW: odds ratio [OR] = 1.002037, 95% confidence interval [CI] = 1.0001150-1.003962, P = 0.03776677), but not on EN (IVW: [OR] = 1.0937191, 95% [CI] = 0.9685831-1.235022, P = 0.1484349) and MM (IVW: [OR] = 0.9998064, 95% [CI] = 0.9994885-1.000124, P = 0.2326482). Besides, a positive causal effect of IBD on NMSC was verified in an independent validation dataset (IVW: [OR] = 1.002651, 95% [CI] = 1.0006524-1.004654, P = 0.009307506). The present study corroborated the causal relationship between IBD and NMSC. In contrast, our results showed no evidence of a causal association of IBD on EN and MM. These findings provide new insights into increasing attention to patients with IBD to prevent concurrent NMSC.
炎症性肠病（IBD）是一种多系统疾病，可影响皮肤系统，即皮肤肠外表现（EIMs）。有人提出，IBD与结节性红斑（EN）、恶性黑色素瘤（MM）和非黑色素瘤皮肤癌（NMSC）有关。然而，IBD与上述皮肤EIMs之间的潜在因果关系仍不清楚。本研究旨在通过孟德尔随机化（MR）设计确定IBD对EN、MM和NMSC的影响。IBD、EN、MM、NMSC的汇总水平数据来自大规模全基因组关联研究。我们在MR分析中使用了五种不同的方法，包括逆方差加权模型（IVW）、MR-Egger、加权中位数、简单模式、加权模式，然后使用Cochran's Q检验、MR-Egger多效性检验、MR-PRESSO全局多效性检验和留一法敏感性检验来评估所识别IVs的异质性和多效性。为了进一步确保我们研究结果的有效性，我们使用F统计量评估工具变量的强度，并估计我们研究的统计效力。使用独立验证数据集以及通过具有不同模型假设的不同MR方法对结果进行了验证。MR分析表明，基因决定的IBD对NMSC有有害的因果效应（IVW：优势比[OR]=1.002037，95%置信区间[CI]=1.0001150-1.003962，P=0.03776677），但对EN（IVW：[OR]=1.0937191，95%[CI]=0.9685831-1.235022，P=0.1484349）和MM（IVW：[OR]=0.9998064，95%[CI]=0.9994885-1.000124，P=0.2326482）没有影响。此外，在独立验证数据集中验证了IBD对NMSC的正向因果效应（IVW：[OR]=1.002651，95%[CI]=1.0006524-1.004654，P=0.009307506）。本研究证实了IBD与NMSC之间的因果关系。相比之下，我们的结果显示没有证据表明IBD与EN和MM之间存在因果关联。这些发现为提高对IBD患者的关注以预防并发NMSC提供了新的见解。
