Polygenic Risk Score in Predicting Esophageal, Oropharyngeal, and Hypopharynx Cancer Risk among Taiwanese Population

Simple Summary In this retrospective study conducted at Taichung Veterans General Hospital, 54,692 participants were examined, including 385 with esophageal, oropharyngeal, or hypopharyngeal squamous cell carcinoma (SCC). Researchers investigated the correlation between cancer incidence and prognosis and a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms. Those with a high PRS (Q4) exhibited a 1.83-fold higher risk of SCCs compared to the low-PRS group (Q1), particularly notable in esophageal and hypopharyngeal cancers. Notably, PGS001087 displayed discernible associations with SCC risk, especially in specific subtypes and advanced stages, although not significantly linked to clinical staging. The study underscores the significance of genetic factors in upper aerodigestive tract cancers, notably esophageal SCC, offering insights for future research and risk assessment strategies. These findings highlight the importance of PRS in understanding cancer susceptibility, guiding targeted interventions, and informing personalized treatment approaches.Abstract Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies.