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Genetic Analysis Reveals PAH As A Risk Factor For Liver Cancer

Pulmonary arterial hypertension (PAH) may contribute to an increased risk of liver cancer, as demonstrated by Mendelian randomization (MR) analysis published recently in Discover Oncology. 

This genetic investigation found that PAH was associated with an 11% higher likelihood of the development of liver cancer (OR, 1.11; 95% CI, 1.01-1.22; P =.025). However, no causal relationships were established between PAH and other common cancers, including thyroid, lung, gastric, or colorectal cancers. These results provide valuable insights into cancer risks in patients with PAH, underscoring the need for further research into underlying biological mechanisms.

This study used summary data from a genome-wide association study for PAH and 5 common types of cancer. Single nucleotide polymorphisms (SNPs) significantly associated with PAH (P <1×10⁻⁶) were selected as instrumental variables for the MR analysis. The primary analytic method, inverse-variance weighted, revealed the association with liver cancer while sensitivity analyses supported the robustness of these results. Tests for heterogeneity and horizontal pleiotropy showed no significant bias, except for mild heterogeneity observed in the MR analysis of lung cancer (P =.049). The MR-Egger intercept test confirmed the absence of horizontal pleiotropy across all analyses (P >.05).

While risk for liver cancer was elevated, no evidence of association was observed for thyroid (OR, 0.95; 95% CI, 0.86-1.06; P =.360), lung (OR, 0.95; 95% CI, 0.90-1.01; P =.129), gastric (OR, 0.97; 95% CI, 0.93-1.02; P =.243), or colorectal (OR, 1.01; 95% CI, 0.98-1.05; P =.412) cancers. Additional sensitivity analyses, including Cochran's Q test, leave-one-out analysis, and funnel plot evaluations, further substantiated the reliability of the results.

Read more about comorbidities of PAH

Instrumental variable validity was ensured by stringent SNP selection criteria, including passing the MR Steiger test and maintaining F-statistics greater than 10. The SNPs used for analysis showed no significant individual impact on the causal associations, supporting the integrity of the study design.

The study highlights a previously underexplored connection between PAH and liver cancer, raising important clinical questions about screening and prevention in high-risk populations. While a direct causal relationship was identified only for liver cancer, the results prompt further exploration into the systemic effects of PAH and its potential role in tumorigenesis.

Future research should aim to elucidate the mechanisms driving the observed association and evaluate potential interventions to mitigate cancer risk in patients with PAH. These efforts could provide crucial advancements in personalized care for this vulnerable population.

"These insights contribute to the growing understanding of the interplay between chronic diseases and cancer, laying a foundation for future research into the underlying mechanisms and therapeutic interventions," concluded the authors.

This article originally appeared on Rare Disease Advisor


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Lysosomes, NCOA7 On The Scene Of Pulmonary Arterial Hypertension

Cardiovascular

Researchers from the University of Pittsburgh School of Medicine have linked pulmonary arterial hypertension (PAH), a progressive disease characterized by blood vessel remodeling, with lysosomal dysfunction and sterol metabolism. They reported their results on Jan. 23, 2025, in Science.

BioWorld Science Cardiovascular



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