Yan Ziqi, Zheng Hongming, Feng Jieni, Li Yiting, Hu Zhifan, Wu Yuan, Liao Guibin, Miao Taosheng, Qiu Zexin, Mo Qiaolan, Li Jia, Lai Ailin, Lu Yue, Chen Bin
Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2024 Oct 8;15:1405503. doi: 10.3389/fphar.2024.1405503. eCollection 2024.
There is a high morbidity of polyps in the digestive tract, and certain subtypes of polyps are thought to induce cancer progression and often recur, which may be associated with chronic inflammation. Mendelian randomization (MR) can help identify potential causative relationships and inform early treatment action.
We performed a bidirectional two-sample MR analysis implementing the results from genome-wide association studies for 41 serum cytokines from 8,293 Finnish individuals, and three types of polyps from European ancestry, respectively, including gastric polyp (6,155 cases vs. 341,871 controls), colonic polyp (22,049 cases vs. 332,368 controls) and gallbladder polyp (458 cases vs. 340,083 controls). Inverse-variance weighted (IVW), weight median (WM), and MR-Egger methods were used for calculating causal estimates. Furthermore, Bayesian model averaging MR (MR-BMA) method was employed to detect the dominant causal circulatory cytokines with adjustment for pleiotropy effects.
Our univariable MR using inverse-variance weight method identified causal associations of IL-2ra (OR: 0.892, 95%CI: 0.828-0.961, p = 0.003), MIG (OR: 1.124, 95%CI: 1.046-1.207, p = 0.001) and IL-18 (OR: 0.912, 95%CI: 0.852-0.977, p = 0.008) with gastric polyp, MIP1b (OR: 0.956, 95%CI: 0.927-0.987, p = 0.005) and IL-6 (OR: 0.931, 95%CI: 0.870-0.995, p = 0.035) with colonic polyp and IL-9 (OR: 0.523, 95%CI: 0.345-0.794, p = 0.0007) with gallbladder polyp. Finally, our MR-BMA analysis prioritized MIG (MIP = 0.332, MACE = 0.022; PP: 0.264, MSCE = 0.059), IL-18 (MIP = 0.302, MACE = -0.020; PP: 0.243, MSCE = -0.059) and IL-2ra (MIP: 0.129; MACE: -0.005; PP: 0.112, MSCE: -0.031) for gastric polyp, and MIP1b (MIP = 0.752, MACE = -0.033; PP: 0.665, MSCE = -0.044) and IL-6 (MIP: 0.196; MACE: -0.012; PP: 0.140, MSCE: -0.064) for colonic polyp, and IL-9 (MIP = 0.936, MACE = -0.446; PP: 0.781, MSCE = -0.478) for gallbladder polyp as the top-ranked protective factors.
Our research advances the current understanding of the function of certain inflammatory biomarker pathways in the genesis and malignant mutation of polyps in the digestive tract. Deeper substantiation is necessary to assess the potential of these cytokines as pharmacological or lifestyle targets for digestive polyps prevention.
消化道息肉的发病率很高，某些息肉亚型被认为会促使癌症进展且常复发，这可能与慢性炎症有关。孟德尔随机化（MR）有助于识别潜在的因果关系并为早期治疗行动提供依据。
我们进行了双向双样本MR分析，分别采用来自8293名芬兰人的41种血清细胞因子以及欧洲血统的三种息肉（包括胃息肉，6155例病例对341871例对照；结肠息肉，22049例病例对332368例对照；胆囊息肉，458例病例对340083例对照）的全基因组关联研究结果。采用逆方差加权（IVW）、加权中位数（WM）和MR-Egger方法计算因果估计值。此外，采用贝叶斯模型平均MR（MR-BMA）方法检测主要的因果循环细胞因子，并对多效性效应进行校正。
我们使用逆方差权重法进行的单变量MR分析确定了IL-2ra（比值比：0.892，95%置信区间：0.828-0.961，p = 0.003）、MIG（比值比：1.124，95%置信区间：1.046-1.207，p = 0.001）和IL-18（比值比：0.912，95%置信区间：0.852-0.977，p = 0.008）与胃息肉的因果关联，MIP1b（比值比：0.956，95%置信区间：0.927-0.987，p = 0.005）和IL-6（比值比：0.931，95%置信区间：0.870-0.995，p = 0.035）与结肠息肉的因果关联，以及IL-9（比值比：0.523，95%置信区间：0.345-0.794，p = 0.0007）与胆囊息肉的因果关联。最后，我们的MR-BMA分析将MIG（MIP = 0.332，MACE = 0.022；PP：0.264，MSCE = 0.059）、IL-18（MIP = 0.302，MACE = -0.020；PP：0.243，MSCE = -0.059）和IL-2ra（MIP：0.129；MACE：-0.005；PP：0.112，MSCE：-0.031）列为胃息肉的首要保护因素，将MIP1b（MIP = 0.752，MACE = -0.033；PP：0.665MSCE = -0.044）和IL-6（MIP：0.196；MACE：-0.012；PP：0.140，MSCE：-0.064）列为结肠息肉的首要保护因素，将IL-9（MIP = 0.936，MACE = -0.446；PP：0.781，MSCE = -0.478）列为胆囊息肉的首要保护因素。
我们的研究推进了目前对某些炎症生物标志物通路在消化道息肉发生和恶性突变中作用的理解。有必要进行更深入的论证，以评估这些细胞因子作为预防消化道息肉的药理学或生活方式靶点的潜力。
