Key result
Genetically proxied pulmonary arterial hypertension is associated with an 11% increased risk of liver cancer (OR 1.11, 95% CI 1.01-1.22, P=0.025).
Why the study?
Previous clinical studies suggested an increased risk of tumor development in patients with PAH, but whether a causal relationship exists remained unclear.
Does genetically proxied pulmonary arterial hypertension increase the risk of common cancers in European populations?
Observational
Does genetically proxied pulmonary arterial hypertension increase the risk of common cancers in European populations?
Genetically proxied pulmonary arterial hypertension is associated with an 11% increased risk of liver cancer, suggesting a potential causal link that warrants further mechanistic investigation.
No immediate change to cancer screening in PAH; MR leaves open whether observational links reflect causality.
BACKGROUND: Previous clinical studies have suggested an increased risk of tumor development in patients with pulmonary arterial hypertension (PAH). However, it remains unclear whether there is a causal relationship between PAH and tumor occurrence. This study investigates the causal link between PAH and cancer from a genetic perspective using Mendelian randomization (MR). METHOD: ) were selected as instrumental variables (IVs). Inverse-variance weighted (IVW) was used as the primary method for MR analysis, with sensitivity analyses including tests for heterogeneity and horizontal pleiotropy. RESULTS: The results from the IVW analysis indicate that genetically proxied PAH is associated with an increased risk of liver cancer [odd ratio (OR) 1.11, 95% confidence interval (CI) 1.01-1.22, P = 0.025), while showing no significant causal relationship with other common types of tumors (thyroid cancer: OR 0.95, 95% CI 0.86-1.06, P = 0.360; lung cancer: OR 0.95, 95% CI 0.90-1.01, P = 0.129; gastric cancer: OR 0.97, 95% CI 0.93-1.02, P = 0.243; colorectal cancer: OR 1.01, 95% CI 0.98-1.05, P = 0.412). Except for the MR analysis examining the causal effect of PAH on lung cancer (P = 0.049), the remaining MR analyses displayed no significant heterogeneity (P > 0.05). Additionally, the MR-Egger intercept test did not find evidence of horizontal pleiotropy (P > 0.05). CONCLUSION: This study highlights that PAH may serve as a potential risk factor for this liver cancer. Future research should aim to elucidate the biological mechanisms at play and explore the potential for early interventions that could mitigate cancer risk in this vulnerable population.
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Fu et al. (2024) conducted an observational in Pulmonary arterial hypertension and cancer. Genetically proxied pulmonary arterial hypertension vs. Unexposed/reference group was evaluated on Risk of liver cancer (OR 1.11, 95% CI 1.01-1.22, p=0.025). Genetically proxied pulmonary arterial hypertension is associated with an 11% increased risk of liver cancer (OR 1.11, 95% CI 1.01-1.22, P=0.025).
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