Investigating Causal Effects of Hematological Traits on Lung Cancer: A Mendelian Randomization Study
Menée à l'aide d'une méthode de randomisation mendélienne et de données pangénomiques, cette étude analyse l'association entre 23 caractéristiques hématologiques et le risque de cancer du poumon par sous-type histologique
Résumé en anglais
Background: Observational studies have suggested blood cell counts may act as predictors of cancer. It is not known whether these hematological traits are causally associated with lung cancer.
Methods: Two-sample bi-directional univariable Mendelian Randomization (MR) and multivariable MR were performed to investigate the causal association between hematological traits and the overall risk of lung cancer and three histological subtypes [lung adenocarcinoma, squamous cell lung cancer (SqCLC), and small cell lung cancer (SCLC)]. The instrumental variables (IVs) of 23 hematological traits were strictly selected from large-scale genome-wide association studies (GWAS). Inverse-variance weighted method and five extra methods were used to obtain robust causal estimates.
Results: We found evidence that genetically influenced higher hematocrit (OR: 0.845, 95%CI: 0.783-0.913, P=1.68×10-5) and hemoglobin concentration (OR: 0.868, 95%CI: 0.804-0.938, P=3.20×10-4) and reticulocyte count (OR: 0.923, 95%CI: 0.872-0.976, P=5.19×10-3) decreased lung carcinoma risk, especially in ever smokers. Multivariable MR (MVMR) further identified hematocrit independently of smoking as an independent predictor. Subgroup analysis showed that a higher plateletcrit level increased the risk of small cell lung carcinoma (OR: 1.288, 95%CI: 1.126-1.474, P=2.25×10-4).
Conclusion: Genetically driven higher levels of reticulocyte count and hematocrit decreased lung cancer risk. Higher plateletcrit had an adverse effect on SCLC. Hematological traits may act as low-cost factors for lung cancer risk stratification.
Impact: Further studies are required to elucidate the potential mechanisms underlying the dysregulation of homeostasis related to hematological traits, such as subclinical inflammation.
