基于孟德尔随机化探讨风湿系统疾病与胰腺癌风险的因果关系
To Investigate the Causal Relationship between Rheumatological Diseases and Pancreatic Cancer Risk Based on Mendelian Randomization

目的：通过两样本孟德尔随机化的方法探究风湿系统疾病(类风湿性关节炎、骨关节炎、系统性红斑狼疮、强直性脊柱炎、痛风)与胰腺癌发病之间的因果关系，为胰腺癌的早期发现提供依据。方法：从全基因组关联分析研究的数据中分别筛出与上述5种风湿系统疾病具有强相关的独立遗传变异作为工具变量，通过孟德尔随机化分析中的逆方差加权法、MR-Egger回归分析和加权中位数法三种方法进行探讨上述5种风湿系统疾病与胰腺癌发病的因果关联。结果：逆方差加权分析法结果：类风湿性关节炎(OR = 1.182, P = 0.013)、骨关节炎(OR = 2.434, P = 0.009)、系统性红斑狼疮(OR = 1.018, P = 0.469)、强直性脊柱炎(OR = 19951683.481, P = 0.040)、痛风(OR = 23.705, P = 0.189)。MR-Egger回归分析结果：类风湿性关节炎(OR = 1.329, P = 0.018)，其余四组结果P > 0.05，统计结果无统计学意义；加权中位数法结果：类风湿性关节炎(OR = 1.265, P = 0.007)，其余四组结果P > 0.05，统计结果无统计学意义。敏感性分析显示研究结果稳健，异质性检验表明不存在异质性。结论：类风湿性关节炎、骨关节炎、强直性脊柱炎与胰腺癌发病存在正向因果关联，在此类患者中定期进行胰腺癌的相关筛查可有利于胰腺癌的早期发现与及时干预。
Objective: Two sample Mendelian randomization method was used to explore the causal relationship between rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, gout and the incidence of pancreatic cancer, so as to provide the basis for the early detection of pancreatic cancer. Methods: From the data of genome-wide association analysis studies, independent genetic variants strongly associated with the above five rheumatic diseases were screened as instrumental variables. The causal relationship between rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, gout and pancreatic cancer was investigated by using the inverse variance weighting method, MR-Egger regression analysis and weighted median method in Mendelian randomized analysis. Results: Inverse variance weighted analysis results: Rheumatoid arthritis (OR = 1.182, P = 0.013), osteoarthritis (OR = 2.434, P = 0.009), systemic lupus erythematosus (OR = 1.018, P = 0.469), ankylosing spondylitis (OR = 19951683.481, P = 0.040), gout (OR = 23.705, P = 0.189). The result of MR-Egger regression analysis: rheumatoid arthritis (OR = 1.329, P = 0.018); the results of the other four groups P > 0.05; the statistical results were not statistically significant. Weighted median method results: rheumatoid arthritis (OR = 1.265, P = 0.007); the results of the other four groups P > 0.05; statistical results were not statistically significant. Sensitivity analysis showed robust results, and heterogeneity test showed no heterogeneity. Conclusion: Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and pancreatic cancer have a positive causal association, and regular screening of pancreatic cancer in these patients can be conducive to early detection and timely intervention of pancreatic cancer.