Sam Li-Sheng Chen1, Jean Ching-Yuan Fann2, Csilla Sipeky3, Teng-Kai Yang4,5, Sherry Yueh-Hsia Chiu6, Amy Ming-Fang Yen1, Virpi Laitinen7, Teuvo L J Tammela8,9, Ulf-Håkan Stenman10, Anssi Auvinen11, Johanna Schleutker12, Hsiu-Hsi Chen5. 1. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University , Taipei. 2. Department of Health Industry Management, School of Healthcare Management, Kainan University , Tao-Yuan , Taiwan. 3. Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku , Turku. 4. Department of Urology, National Taiwan University Hospital , Taipei. 5. Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University , Taipei. 6. Department and Graduate Institute of Health Care Management, College of Management, Chang Gung University , Tao-Yuan , Taiwan. 7. Institute of Biomedical Technology/BioMediTech, University of Tampere , Tampere. 8. Faculty of Medicine and Biosciences, University of Tampere , Tampere. 9. Department of Urology, Tampere University Hospital , Tampere. 10. Department of Clinical Chemistry, Helsinki University Central Hospital and Faculty of Medicine, University of Helsinki , Helsinki , Finland. 11. Section of Health Sciences, Faculty of Social Sciences, University of Tampere , Tampere. 12. Department of Medical Genetics, Turku University Hospital , Turku.
Abstract
PURPOSE: Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information. MATERIALS AND METHODS: We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study. A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above. RESULTS: The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined. CONCLUSIONS: Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.
PURPOSE: Combined information on single nucleotide polymorphisms and prostate specific antigen offers opportunities to improve the performance of screening by risk stratification. We aimed to predict the risk of prostate cancer based on prostate specific antigen together with single nucleotide polymorphism information. MATERIALS AND METHODS: We performed a prospective study of 20,575 men with prostate specific antigen testing and 4,967 with a polygenic risk score for prostate cancer based on 66 single nucleotide polymorphisms from the Finnish population based screening trial of prostate cancer and 5,269 samples of 7 single nucleotide polymorphisms from the Finnish prostate cancer DNA study. A Bayesian predictive model was built to estimate the risk of prostate cancer by sequentially combining genetic information with prostate specific antigen compared with prostate specific antigen alone in study subjects limited to those with prostate specific antigen 4 ng/ml or above. RESULTS: The posterior odds of prostate cancer based on 7 single nucleotide polymorphisms together with the prostate specific antigen level ranged from 3.7 at 4 ng/ml, 14.2 at 6 and 40.7 at 8 to 98.2 at 10 ng/ml. The ROC AUC was elevated to 88.8% (95% CI 88.6-89.1) for prostate specific antigen combined with the risk score based on 7 single nucleotide polymorphisms compared with 70.1% (95% CI 69.6-70.7) for prostate specific antigen alone. It was further escalated to 96.7% (95% CI 96.5-96.9) when all prostate cancer susceptibility polygenes were combined. CONCLUSIONS: Expedient use of multiple genetic variants together with information on prostate specific antigen levels better predicts the risk of prostate cancer than prostate specific antigen alone and allows for higher prostate specific antigen cutoffs. Combined information also provides a basis for risk stratification which can be used to optimize the performance of prostate cancer screening.
Entities:
Keywords:
mass screening; polymorphism; prostate-specific antigen; prostatic neoplasms; risk; single nucleotide
Authors: Jerry Zeng Yang Wong; Jia Hui Chai; Yen Shing Yeoh; Nur Khaliesah Mohamed Riza; Jenny Liu; Yik-Ying Teo; Hwee Lin Wee; Mikael Hartman Journal: BMC Health Serv Res Date: 2021-04-23 Impact factor: 2.655