2267P - Coronary heart disease and risk of lung cancer: A two-sample Mendelian randomization study

Background

Observational studies have suggested an association between coronary heart disease and increased risk of lung cancer, but the causal relationship between these two conditions remains uncertain. Therefore, we conducted a two-sample Mendelian randomization study to investigate whether there is a causal relationship between coronary heart disease and higher risk of lung cancer.

Methods

We utilized 37 single nucleotide polymorphisms (SNPs) associated with coronary heart disease (with a p-value <5x10^-8) from a genome-wide association study involving 184,305 European individuals in the CARDIoGRAMplusC4D Consortium as instrumental variables. Summary data for lung cancer were obtained from the International Lung Cancer Consortium, including 11,348 cases and 15,861 controls. We conducted primary MR analysis using the inverse-variance weighted method and evaluated the MR assumptions in sensitivity analyses. Subgroup analyses were performed for different histological subtypes of lung cancer, and all analyses were carried out using the TwoSampleMR package in R.

Results

The MR analysis revealed that a genetic predisposition to coronary heart disease had a protective effect against the development of lung cancer, with an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.78-0.99, P=0.035). Subgroup analyses indicated a decreased risk for squamous cell lung cancer (OR 0.80, 95% CI 0.68-0.93, P=0.004), but no significant association was observed in lung adenocarcinoma (OR = 0.87; 95% CI 0.73-1.03, P=0.106). Sensitivity analyses supported a causal interpretation of the findings, indicating that major bias from genetic pleiotropy was unlikely.

Conclusions

Contrary to findings from previous observational studies, our results suggest that coronary heart disease may have a protective effect against the development of lung cancer. These findings emphasize the need to further investigate the underlying mechanisms linking these two conditions and provide a foundation for future research in this field.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Caichen Li.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.