系统性硬皮病与肺癌风险的关联：队列研究荟萃分析和孟德尔随机化分析的结果。

Association between systemic sclerosis and risk of lung cancer: results from a pool of cohort studies and Mendelian randomization analysis.

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, Jingxiu Road, Panyu District, Guangzhou 511436, China.

出版信息

Autoimmun Rev. 2020 Oct;19(10):102633. doi: 10.1016/j.autrev.2020.102633. Epub 2020 Aug 13.

DOI:10.1016/j.autrev.2020.102633

PMID:32801043

Abstract

BACKGROUND

Population-based cohort studies have indicated that systemic sclerosis (SSc) may be associated with an increased risk of lung cancer. However, there are few studies that comprehensively investigate their correlation and the causal effect remains unknown.

METHODS

A systematic search of PubMed, Web of Science, Cochrane Library and Embase from the inception dates to December 1, 2019 was carried out. Meta-analysis was performed to calculate odds ratio (OR) and corresponding 95% confidence interval (CI) using random-effects models. Subgroup analyses were performed regarding gender. Two-sample Mendelian randomization (MR) was carried out with summary data from published genome-wide association studies of SSc (Neale Lab, 3871 individuals; UK Biobank, 463,315 individuals) and lung cancer (International Lung Cancer Consortium, 27,209 individuals; UK Biobank, 508,977 individuals). Study-specific estimates were summarized using inverse variance-weighted, weighted median, and MR-Egger method.

RESULTS

Through meta-analysis of 10 population-based cohort studies involving 12,218 patients, we observed a significantly increased risk of lung cancer among patients with SSc (OR 2.80, 95% CI 1.55-5.03). In accordance with subgroup analysis, male patients (OR 4.11, 95% CI 1.92-8.79) had a 1.5-fold higher lung cancer risk compared with female patients (OR 2.73, 95% CI 1.41-5.27). However, using a score of 11 SSc-related single nucleotide polymorphisms (p < 5*10) as instrumental variables, the MR study did not support a causality between SSc and lung cancer (OR 1.001, 95% CI 0.929-1.100, p = 0.800). Specifically, subgroup MR analyses indicated that SSc was not associated with increased risks of non-small-cell lung cancer (OR 1.000, 95% CI 0.999-1.000, p = 0.974), including lung adenocarcinoma (OR 0.996, 95% CI 0.906-1.094, p = 0.927), squamous cell lung carcinoma (OR 1.034, 95% CI 0.937-1.140, p = 0.507), nor small-cell lung cancer (OR 1.000, 95% CI 0.999-1.000, p = 0.837).

CONCLUSIONS

This study indicated an increased risk of lung cancer among patients with SSc by meta-analysis, whereas the MR study did not support a causality between the two diseases. Further studies are warranted to investigate the factors underlying the attribution of SSc to lung cancer risk.

摘要

背景

基于人群的队列研究表明，系统性硬化症（SSc）可能与肺癌风险增加有关。然而，很少有研究全面调查它们之间的相关性，因果关系仍不清楚。

方法

从建立日期到 2019 年 12 月 1 日，对 PubMed、Web of Science、Cochrane 图书馆和 Embase 进行了系统检索。使用随机效应模型计算优势比（OR）和相应的 95%置信区间（CI）进行荟萃分析。根据性别进行了亚组分析。使用来自 SSc（Neale 实验室，3871 人；英国生物库，463315 人）和肺癌（国际肺癌联合会，27209 人；英国生物库，508977 人）的已发表全基因组关联研究的汇总数据进行两样本孟德尔随机化（MR）分析。使用逆方差加权、加权中位数和 MR-Egger 方法总结研究特异性估计值。

结果

通过对 10 项基于人群的队列研究中 12218 名患者进行荟萃分析，我们观察到 SSc 患者肺癌风险显著增加（OR 2.80，95%CI 1.55-5.03）。根据亚组分析，与女性患者（OR 2.73，95%CI 1.41-5.27）相比，男性患者（OR 4.11，95%CI 1.92-8.79）的肺癌风险增加了 1.5 倍。然而，使用 11 个 SSc 相关的单核苷酸多态性（p < 5*10）作为工具变量进行分数 MR 研究，并不支持 SSc 和肺癌之间存在因果关系（OR 1.001，95%CI 0.929-1.100，p = 0.800）。具体来说，亚组 MR 分析表明，SSc 与非小细胞肺癌（OR 1.000，95%CI 0.999-1.000，p = 0.974）、包括肺腺癌（OR 0.996，95%CI 0.906-1.094，p = 0.927）、鳞状细胞肺癌（OR 1.034，95%CI 0.937-1.140，p = 0.507）和小细胞肺癌（OR 1.000，95%CI 0.999-1.000，p = 0.837）的风险增加无关。