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

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.