Assessing thyroid cancer risk using polygenic risk scores
pmid: 32132206
pmc: PMC7084156
Assessing thyroid cancer risk using polygenic risk scores
Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results to build polygenic risk score (PRS) models in three PTC study groups from Ohio (1,544 patients and 1,593 controls), Iceland (723 patients and 129,556 controls), and the United Kingdom (534 patients and 407,945 controls). A PRS based on the 10 established PTC SNPs showed a stronger predictive power compared with the clinical factors model, with a minimum increase of area under the receiver-operating curve of 5.4 percentage points ( P ≤ 1.0 × 10 −9 ). Adding an extended PRS based on 592,475 common variants did not significantly improve the prediction power compared with the 10-SNP model, suggesting that most of the remaining undiscovered genetic risk in thyroid cancer is due to rare, moderate- to high-penetrance variants rather than to common low-penetrance variants. Based on the 10-SNP PRS, individuals in the top decile group of PRSs have a close to sevenfold greater risk (95% CI, 5.4–8.8) compared with the bottom decile group. In conclusion, PRSs based on a small number of common germline variants emphasize the importance of heritable low-penetrance markers in PTC.
- University of Iceland Iceland
- Utrecht University Netherlands
- THE OHIO STATE UNIVERSITY United States
- Radboud University Nijmegen Netherlands
- The University of Texas MD Anderson Cancer Center United States
Adult, Male, Multifactorial Inheritance, DNA Mutational Analysis, Iceland, Radboud University Medical Center, Thyroid Neoplasms/epidemiology, Penetrance, Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences, Thyroid Gland/pathology, Polymorphism, Single Nucleotide, Risk Assessment, Thyroid cancer, Cohort Studies, Polygenic risk score, Research Support, N.I.H., Extramural, Predictive Value of Tests, Risk Factors, Journal Article, Biomarkers, Tumor, GWAS, Humans, Genetic Predisposition to Disease, Internal Medicine - Radboud University Medical Center, Risk Assessment/methods, General, Iceland/epidemiology, Models, Genetic, United Kingdom/epidemiology, Pathology - Radboud University Medical Center, Middle Aged, Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences, United States/epidemiology, Risk prediction, Multicenter Study, ROC Curve, Thyroid Cancer, Papillary/epidemiology, Case-Control Studies, Urology - Radboud University Medical Center, Female, Biomarkers, Tumor/genetics, Health Evidence - Radboud University Medical Center, Genome-Wide Association Study
Adult, Male, Multifactorial Inheritance, DNA Mutational Analysis, Iceland, Radboud University Medical Center, Thyroid Neoplasms/epidemiology, Penetrance, Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences, Thyroid Gland/pathology, Polymorphism, Single Nucleotide, Risk Assessment, Thyroid cancer, Cohort Studies, Polygenic risk score, Research Support, N.I.H., Extramural, Predictive Value of Tests, Risk Factors, Journal Article, Biomarkers, Tumor, GWAS, Humans, Genetic Predisposition to Disease, Internal Medicine - Radboud University Medical Center, Risk Assessment/methods, General, Iceland/epidemiology, Models, Genetic, United Kingdom/epidemiology, Pathology - Radboud University Medical Center, Middle Aged, Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life Sciences, United States/epidemiology, Risk prediction, Multicenter Study, ROC Curve, Thyroid Cancer, Papillary/epidemiology, Case-Control Studies, Urology - Radboud University Medical Center, Female, Biomarkers, Tumor/genetics, Health Evidence - Radboud University Medical Center, Genome-Wide Association Study
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