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  1. Home
  2. Causal Linkage Between Angiotensin-converting Enzyme 2 And Risk Of Lung Cancer: A Bidirectional Two-sample Mendelian Randomization Study.
  1. Home
  2. Causal Linkage Between Angiotensin-converting Enzyme 2 And Risk Of Lung Cancer: A Bidirectional Two-sample Mendelian Randomization Study.

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Causal linkage between angiotensin-converting enzyme 2 and risk of lung cancer: a bidirectional two-sample Mendelian

Shubin Chen1, Ruiling Ning1, Wei Jiang1

  • 1Medical Oncology of Respiratory, Guangxi Medical University Cancer Hospital, Nanning, China.

Frontiers in Medicine
|July 23, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Angiotensin-converting enzyme 2 (ACE2) is causally linked to a reduced risk of lung cancer. This genetic association suggests potential public health strategies for lung cancer prevention.

Keywords:
GWAS datasetMendelian randomization studyangiotensin-converting enzyme 2causal risk factorslung cancer

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Area of Science:

  • Genetics and Epidemiology
  • Cardiovascular and Respiratory Medicine

Background:

  • Observational studies indicate a potential association between angiotensin-converting enzyme 2 (ACE2) and lung cancer.
  • Confounding variables may obscure the true relationship between ACE2 and lung cancer risk.
  • Clarifying the ACE2-lung cancer link is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To investigate the causal relationship between angiotensin-converting enzyme 2 (ACE2) and the risk of developing lung cancer.
  • To differentiate genetic predisposition from environmental factors influencing lung cancer risk.

Main Methods:

  • Selection of single nucleotide polymorphisms (SNPs) strongly associated with ACE2.
  • Utilized lung cancer genome-wide association study (GWAS) data for relevant SNPs.
  • Employed two-sample Mendelian randomization (MR) analysis to assess causality, including reverse MR for directionality.
  • Main Results:

    • Significant evidence supports ACE2's causal role in decreasing lung cancer risk (OR: 0.94, 95% CI: 0.90-0.98, P=0.0016).
    • MR analyses (IVW, MR-Egger, MR-PRESSO) confirmed no significant heterogeneity, horizontal pleiotropy, or outlier SNPs.
    • Leave-one-out analysis demonstrated robust and consistent findings; reverse MR showed no significant causal effect from lung cancer to ACE2.

    Conclusions:

    • Mendelian randomization analysis reveals a significant causal link between ACE2 and reduced lung cancer risk.
    • Findings suggest ACE2 status could be a factor in lung cancer incidence.
    • Implications for public health strategies targeting lung cancer prevention are highlighted.