0037 Investigating Common Genetic Factors Between Obstructive Sleep Apnea and Prostate Cancer

Allan Porcacchia,Mariana Moysés-Oliveira, Gabriel Pires,Monica Andersen,Sergio Tufik

SLEEP(2024)

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摘要
Abstract Introduction Cancer is one of the leading causes of death in the world. Studies have highlighted the possible association between obstructive sleep apnea (OSA) and an increased risk of incidence or prevalence of some types of cancer, especially prostate cancer. However, the extent to which genes that are related to both conditions contribute to their comorbidity is still unclear. The aim of this study was to evaluate the intersection of risk genes found in both OSA and prostate cancer. Methods Two sets of genes associated respectively with OSA and prostate cancer were manually curated and then compared to obtain an intersection gene list. Fisher’s exact test was employed to evaluate the statistical significance of the overlap, with a significance threshold of p-value< 0.05. The identification of enriched pathways among the intersection gene list was performed using the Benjamini–Hochberg test, with a significance threshold of adjusted p-value< 0.05. A functional network was generated from the intersect gene list which was used as an input in a protein–protein interaction analysis conducted using the String database. Results Sixty-eight genes overlapped between prostate cancer risk genes and OSA-associated genes, indicating more overlap than expected by chance (odds ratio=2.665; p=2.606E–10). This intersect list was associated mainly with hypoxia, apoptosis, oxidative stress, and cell cycle, proliferation, or cell damage. The hypoxia-inducible factor (HIF)-1 signaling pathway stands out from the list of enriched pathways reported in both conditions (adjusted p-value< 0.0006). A 17-node network was retrieved from the overlapping gene list and included key proteins from the aforementioned enriched pathways, which comprised TNF, STAT3, BCL-2, TGF, and ATM. Conclusion The genetic basis of prostate cancer and OSA was significantly shared, indicating common molecular etiology in respect of this comorbidity. Relevant proliferation, apoptosis, and hypoxia pathways were significantly enriched among the genes associated with both conditions, suggesting their role in pathophysiological processes. Support (if any) Associação Fundo de Incentivo à Pesquisa (AFIP); Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
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