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

Haoxin Peng; Xiangrong Wu; Yaokai Wen; Caichen Li; Jinsheng Lin; Jianfu Li; Shan Xiong; Ran Zhong; Hengrui Liang; Bo Cheng; Jun Liu; Jianxing He; Wenhua Liang

doi:10.1016/j.autrev.2020.102633

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

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

Authors

Haoxin Peng¹, Xiangrong Wu¹, Yaokai Wen¹, Caichen Li², Jinsheng Lin³, Jianfu Li², Shan Xiong², Ran Zhong², Hengrui Liang², Bo Cheng², Jun Liu², Jianxing He⁴, Wenhua Liang⁵

Affiliations

¹ 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.
² 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.
³ Nanshan School, Guangzhou Medical University, Jingxiu Road, Panyu District, Guangzhou 511436, China.
⁴ 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. Electronic address: drjianxing.he@gmail.com.
⁵ 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. Electronic address: liangwh1987@163.com.

PMID: 32801043
DOI: 10.1016/j.autrev.2020.102633

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^-8) 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.

Keywords: Lung cancer risk; Mendelian randomization; Meta-analysis; Systemic sclerosis.

Publication types

Meta-Analysis

MeSH terms

Carcinoma, Non-Small-Cell Lung*
Cohort Studies
Female
Genome-Wide Association Study
Humans
Lung Neoplasms* / epidemiology
Male
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Risk
Scleroderma, Systemic* / epidemiology