系统性红斑狼疮与肺癌之间的关联：队列研究汇总及孟德尔随机化分析结果
Association between systemic lupus erythematosus and lung cancer: results from a pool of cohort studies and Mendelian randomization analysis.
作者信息
Peng Haoxin, Li Caichen, Wu Xiangrong, Wen Yaokai, Lin Jinsheng, Liang Hengrui, Zhong Ran, Liu Jun, He Jianxing, Liang Wenhua
机构信息
Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Nanshan School, Guangzhou Medical University, Guangzhou, China.
出版信息
J Thorac Dis. 2020 Oct;12(10):5299-5302. doi: 10.21037/jtd-20-2462.
BACKGROUND
Epidemiological evidence suggested that systemic lupus erythematosus (SLE) might be correlated with an increased risk of lung cancer. Nevertheless, few studies have comprehensively investigated their correlation and the causal effect remains unclear. With a meta-analysis and Mendelian randomization (MR) approach, we were able to systematically investigate the relationship between SLE and lung cancer risk.
METHODS
A systematic search of cohort studies was conducted using network databases from the inception dates to February 1, 2020. Meta-analysis was performed to calculate standardized incidence rate (SIR) and their 95% CI. Furthermore, utilizing 33 SLE-related single nucleotide polymorphisms as instrumental variables (IVs) identified by the latest genome-wide association studies (GWASs), we investigated the correlation between genetically predisposed SLE and lung cancer risk using summary statistics from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). The Inverse variance-weighted method was applied to estimate the causality and we further evaluated the pleiotropy by means of the weighted median and the MR-Egger regression method. Subgroup analysis according to different histotypes of lung cancer was also conducted.
RESULTS
Through meta-analysis of 15 cohort studies involving 110,519 patients, we observed an increased risk of lung cancer among SLE patients (SIR =1.63, 95% CI, 1.39-1.90). Subgroup analysis suggested that female patients (SIR =1.28, 95% CI, 1.13-1.44) have a relatively higher lung cancer risk compared with male patients (SIR =1.15, 95% CI, 1.02-1.30). MR analysis indicated that genetically predisposed SLE was causally associated with an increased lung cancer risk (OR =1.045, 95% CI, 1.005-1.086, P=0.0276). When results were examined by histotypes, a causal relationship was observed between genetically predisposed SLE and squamous cell lung cancer (OR =1.065, 95% CI, 1.002-1.132, P=0.0429). Additionally, the results demonstrated the absence of the horizontal pleiotropy.
CONCLUSIONS
Both meta-analysis and MR analysis results suggested that SLE was associated with an increased lung cancer risk. Further investigations are warranted to investigate the etiology underlying the attribution of SLE to lung cancer.
背景
流行病学证据表明，系统性红斑狼疮（SLE）可能与肺癌风险增加相关。然而，很少有研究全面调查它们之间的相关性，因果关系仍不明确。通过荟萃分析和孟德尔随机化（MR）方法，我们能够系统地研究SLE与肺癌风险之间的关系。
方法
使用网络数据库从起始日期到2020年2月1日对队列研究进行系统检索。进行荟萃分析以计算标准化发病率（SIR）及其95%置信区间。此外，利用最新的全基因组关联研究（GWAS）确定的33个与SLE相关的单核苷酸多态性作为工具变量（IV），我们使用国际肺癌联盟的汇总统计数据（11348例病例和15861例对照）研究遗传易感性SLE与肺癌风险之间的相关性。应用逆方差加权法估计因果关系，并通过加权中位数和MR-Egger回归方法进一步评估多效性。还根据肺癌的不同组织学类型进行了亚组分析。
结果
通过对涉及110519名患者的15项队列研究的荟萃分析，我们观察到SLE患者患肺癌的风险增加（SIR = 1.63，95%置信区间，1.39 - 1.90）。亚组分析表明，女性患者（SIR = 1.28，95%置信区间，1.13 - 1.44）与男性患者（SIR = 1.15，95%置信区间，1.02 - 1.30）相比，患肺癌的风险相对较高。MR分析表明，遗传易感性SLE与肺癌风险增加存在因果关系（OR = 1.045，95%置信区间，1.005 - 1.086，P = 0.0276）。当按组织学类型检查结果时，观察到遗传易感性SLE与肺鳞状细胞癌之间存在因果关系（OR = 1.065，95%置信区间，1.002 - 1.132，P = 0.0429）。此外，结果表明不存在水平多效性。
结论
荟萃分析和MR分析结果均表明，SLE与肺癌风险增加相关。有必要进一步研究SLE与肺癌之间归因的潜在病因。
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