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Presumed Pathogenic Germ Line and Somatic Variants in African American Thyroid Cancer.
Zachary A Hurst1,2, Sandya Liyanarachchi3, Pamela Brock4
1Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, Ohio, USA.
Thyroid : Official Journal of the American Thyroid Association
|December 8, 2023
Summary
African American thyroid cancer patients may have worse outcomes due to healthcare disparities rather than genetics. Further research is needed on genetic variants influencing cancer risk and cardiovascular events.
Area of Science:
- Genomics
- Oncology
- Cardiovascular Medicine
Background:
- African American (AA) patients with nonmedullary thyroid cancer (NMTC) often have poorer prognoses compared to European Americans (EA).
- This disparity is potentially linked to healthcare access issues and underlying genetic variations.
- Investigating genetic factors in AA NMTC patients is crucial for understanding outcome differences.
Purpose of the Study:
- To analyze the impact of germline and somatic variants on clinical outcomes in African American NMTC patients.
- To identify presumed pathogenic germline or somatic variants (PPGVs/PPSVs) in cancer-related and cardiovascular risk genes.
- To explore the potential role of genetic variants in cancer progression and treatment response.
Main Methods:
- Whole-exome sequencing of germline DNA (blood/normal tissue) and paired tumor DNA from 37 AA NMTC patients.
- Identification of variants with a Combined Annotation Depletion Dependent (CADD) score ≥20 and VarSome Clinical classification of likely pathogenic or pathogenic.
- Analysis of PPGVs/PPSVs in cancer-related genes, cardiovascular risk genes, and their association with African ancestry.
Main Results:
- 17 PPGVs were found in 16 cancer-related genes, with *WRN* being previously linked to NMTC.
- *BRAF* was the most frequent somatic variant (41% of tumors).
- One patient with *ERCC4* PPGV and *TP53* PPSV died from PTC/ATC; *SC5NA*, *GYG1*, *CBS*, *CFTR*, and *SI* PPGVs were noted in cardiovascular risk genes.
Conclusions:
- Most AA-NMTC patients in this cohort had favorable outcomes post-treatment, suggesting healthcare disparities are a primary driver of worse prognoses.
- The clinical significance of PPGVs that may promote *TP53* mutations or predispose to cardiovascular events requires further investigation.
- Integrated analysis of PPGV/PPSV profiles could aid in identifying high-risk NMTC patients needing closer monitoring or proactive interventions.
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