Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization
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ORIGINAL ARTICLE – CANCER RESEARCH
Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization analyses Yu Jiang1,2,3,4,5 · Zixuan Su1,2,3,4,5 · Caichen Li1,2,3,4 · Runchen Wang1,2,3,4,5 · Yaokai Wen1,2,3,4,5 · Hengrui Liang1,2,3,4 · Jianxing He1,2,3,4,6 · Wenhua Liang1,2,3,4,6 Received: 10 July 2020 / Accepted: 16 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose We aimed to elucidate the associations between aspirin use with risk of lung cancer, by conducting a meta-analysis and Mendelian randomization (MR) analyses from published Genome-Wide Association Studies (GWAS). Methods Cohort studies, nested case–control studies, and randomized controlled trials (RCTs) investigating the impact of aspirin exposure and lung cancer incidence were included. Relative risk (RR) and its 95% confidence interval (CI) were evaluated in eligible studies. Subgroup analyses regarding gender, pathologic subtypes and smoking status were also executed. MR analyses were conducted using summary statistics obtained from two large consortia [Neale Lab and International Lung Cancer Consortium (ILCCO)] to assess the possible causal relationship of aspirin on lung cancer incidence. Results Sixteen eligible studies involving 1,522,687 patients were included. The combined RR of aspirin use for the incidence of lung cancer was 0.95 (95% confidence interval (CI) 0.91–0.98). In subgroup meta-analyses, a significant protective effect was observed in squamous cell lung cancer (RR = 0.80; 95% CI 0.65–0.98). In terms of gender, the chemopreventive value was only observed among men (RR = 0.87; 95% CI 0.77–0.97). The MR risk analysis suggested a causal effect of aspirin on lung cancer incidence, with evidence of a decreased risk for overall lung cancer (OR = 0.042; 95% CI 0.003–0.564) and squamous cell lung cancer (OR = 0.002; 95% CI 1.21 × 10–5–0.301). Conclusion Our study provided evidence for a causal protective effect of aspirin on the risk of lung cancer incidence among men, particularly on the squamous cell lung cancer risk. Keywords Aspirin · Lung cancer · Meta-analysis · Causality · Mendelian randomization
Jianxing He and Wenhua Liang are joint corresponding authors. Yu Jiang, Zixuan Su and Caichen Li are co-first authors and contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03394-5) contains supplementary material, which is available to authorized users.
Abbreviations CI Confidence interval COX Cyclooxygenase GWAS Genome-Wide Association Studies ILCCO International Lung Cancer Consortium IVs Instrumental variables IVW Inverse-variance weighted LD Linkage disequilibrium MR Mendelian randomization
* Jianxing He [email protected]
3
National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China
* Wenhua Liang [email protected]
4
Guangzhou Institute of Respiratory Health, Guangzhou 510120, China
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