ArticleJAMA otolaryngology-- head & neck surgery2025
Polygenic Score for Clinicopathologic Features and Survival Outcomes in Papillary Thyroid Carcinoma.
Article in JAMA otolaryngology-- head & neck surgery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Importance: Genome-wide association studies have identified germline variants associated with the development of papillary thyroid carcinoma (PTC) that can be used to construct a polygenic score (PGS). It is important to determine whether patients with higher germline genetic risk, as summarized using PGS, present with more aggressive disease and/or develop worse clinical outcomes. Objective: To assess whether germline risk defined by PGS is associated with clinicopathologic features and survival outcomes for patients with PTC. Design, Setting, and Participants: This retrospective cohort study included patients with newly diagnosed PTC who presented to The University of Texas MD Anderson Cancer Center for treatment between 1999 and 2014, with a median follow-up of 12 years. Data were analyzed from December 2023 to April 2024. Exposure: Germline risk, as defined by PGS. Main Outcomes and Measures: Genomic DNA was extracted from buffy coat cells isolated from peripheral blood samples, and genotyping for germline polymorphisms was performed. Germline risk for PTC was estimated with a previously validated PGS calculated from 10 single-nucleotide variations identified through genome-wide association studies. Stage; PTC-specific survival, defined as the time from PTC diagnosis to death caused by PTC; and overall survival, defined as the time from PTC diagnosis to death by any cause, were analyzed. Results: A total of 366 patients were included in the study (261 women [71.3%]; mean [SD] age at diagnosis, 44.3 [13.8] years). There was a statistically significant association between higher PGS and multifocality (β [SE], 0.40 [0.23]; P = .045) and cervical lymph node involvement (N stage) (β [SE], 0.62 [0.35]; P = .009) at diagnosis. PGS was associated with PTC-specific survival (hazard ratio, 2.66; 95% CI, 1.03-6.85; P = .04), but this association was not independent of age and overall stage. There was not a statistically significant association between PGS and overall survival. Conclusions and Relevance: Findings of this cohort study suggest that patients with a higher germline risk of PTC, as estimated by PGS, present with more aggressive clinicopathologic features. These results contribute to the current understanding of inherited risk in PTC and how germline variants could potentially contribute to disease presentation and clinical outcomes.
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