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Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization analyses

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

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.

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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

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OR:

Odds ratio

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

RCTs:

Randomized controlled trials

RR:

Relative risk

SNPs:

Single nucleotide polymorphisms

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Acknowledgements

This work was supported by the National Key R&D Program of China [2016YFC0905400]; China National Science Foundation [81871893, 81501996]; Key Project of Guangzhou Scientific Research Project [201804020030]; High-level university construction project of Guangzhou Medical University [20182737, 201721007, 201715907, 2017160107]; IVATS National key R&D Program [2017YFC0907903, 2017YFC0112704] and Application, industrialization and generalization of surgical incision protector [2011B090400589]. The authors acknowledge the efforts of the consortia in providing high-quality GWAS resources for researchers. Data and materials are available from corresponding the GWAS consortium. We also appreciate the authors of the original meta-analysis for their contribution to this topic. The authors thank Ms. Ran Zhong and Ms. Lindsey Hamblin for helping to edit the manuscript. The authors would like to thank the editors and the anonymous reviewers for their valuable comments and suggestions to improve the quality of the paper.

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Author notes

  1. Yu Jiang, Zixuan Su and Caichen Li are co-first authors and contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China

    Yu Jiang, Zixuan Su, Caichen Li, Runchen Wang, Yaokai Wen, Hengrui Liang, Jianxing He & Wenhua Liang

  2. State Key Laboratory of Respiratory Disease, Guangzhou, 510120, China

    Yu Jiang, Zixuan Su, Caichen Li, Runchen Wang, Yaokai Wen, Hengrui Liang, Jianxing He & Wenhua Liang

  3. National Clinical Research Center for Respiratory Disease, Guangzhou, 510120, China

    Yu Jiang, Zixuan Su, Caichen Li, Runchen Wang, Yaokai Wen, Hengrui Liang, Jianxing He & Wenhua Liang

  4. Guangzhou Institute of Respiratory Health, Guangzhou, 510120, China

    Yu Jiang, Zixuan Su, Caichen Li, Runchen Wang, Yaokai Wen, Hengrui Liang, Jianxing He & Wenhua Liang

  5. Nanshan School, Guangzhou Medical University, Jingxiu Road, Panyu District, Guangzhou, 511436, China

    Yu Jiang, Zixuan Su, Runchen Wang & Yaokai Wen

  6. China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou, China

    Jianxing He & Wenhua Liang

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Contributions

YJ and WHL were responsible for the concept and design of the study, interpretation of data, and drafting and writing of the article. The other authors were responsible for interpretation of data and revision of the intellectual content. All authors participated in final approval of the article and agreed to be accountable for all aspects of the work.

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Correspondence to Jianxing He or Wenhua Liang.

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All authors declare no conflicts of interest.

Ethical approval

There are no patients involved in our study design, recruitment or research conduction, and thus, there is no need for ethical approval. No patient was asked to make recommendations about the interpretation or writing of the results. There are no plans to disseminate the results of the study to the study participants or relevant patient communities. Thus, there is no need for informed consent in our study.

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The data sets generated and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

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The computer code generated and/or analyzed during the current study is not publicly available, but is available from the corresponding author on reasonable request.

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Jianxing He and Wenhua Liang are joint corresponding authors.

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Jiang, Y., Su, Z., Li, C. et al. Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization analyses. J Cancer Res Clin Oncol 147, 139–151 (2021). https://doi.org/10.1007/s00432-020-03394-5

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  • DOI: https://doi.org/10.1007/s00432-020-03394-5

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