Year: 2023
Type: review
Study design: Observational Study
Abstract: ABSTRACT Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. We discovered 128 genome-wide significant associations ( P <5×10 -8 ) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGS PSA ) that explains 9.61% of constitutive PSA variation. We found that in men of European ancestry, using PGS-adjusted PSA would avoid 31% of negative prostate biopsies, but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR)=3.44, P =6.2×10 -14 ; AUC=0.755) than unadjusted PSA (OR=3.31, P =1.1×10 -12 ; AUC=0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC=0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC=0.786, P =7.2×10 -4 ). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.
Source: Nature Medicine
Authors: Linda Kachuri, Thomas J. Hoffmann, Yu Jiang, Sonja I. Berndt, John P. Shelley, Kerry R. Schaffer, Mitchell J. Machiela, Neal D. Freedman, Wen-Yi Huang, Shengchao A. Li, Ryder Easterlin, Phyllis J. Goodman, Cathee Till, Ian Thompson, Hans Lilja, Stephen K. Van Den Eeden, Stephen J. Chanock, Christopher A. Haiman, David V. Conti, Robert J. Klein, Jonathan D. Mosley, Rebecca E. Graff, John S. Witte
Institutions: University of California, San Francisco, Stanford Medicine, Stanford Cancer Institute, Stanford University, Division of Cancer Epidemiology and Genetics, Vanderbilt University Medical Center, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Fred Hutch Cancer Center, Christus Santa Rosa Health System, Memorial Sloan Kettering Cancer Center, Lund University, Skåne University Hospital, Kaiser Permanente, Kaiser Permanente Northern California, University of Southern California, USC Norris Comprehensive Cancer Center, Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Awards: G1007166040, G1901299981, G2542880440, G2702338508, G2849661646, G289723095, SWOG NCORP Research Base, G3539824434, Medical Scientist Training Program, Big Omics Data Engine 2 Supercomputer, Genetic Predictors of Prostate Cancer Survival, BMI Bioinformatics Training Grant, G5374026869, Comprehensive Investigation of Multiple Myeloma Genetic Susceptibility in African Americans, G5909954444, Improving prostate cancer screening by integration of SNPs with blood biomarkers, G693075998, Comprehensive Investigation of Multiple Myeloma Genetic Susceptibility in African Americans, G811166696, Leveraging common genetic variation to reduce misclassification of non-diseased individuals and unnecessary health care utilization attributable to surrogate biomarkers, G896527435, G8966693843, Cancer Center Support Grant, Precision Prostate Cancer Screening with Genetically Adjusted Prostate-Specific Antigen Levels, SPORE in Prostate Cancer, Leveraging Prospective Cancer Epidemiology Cohorts and Novel Methods to Improve Polygenic Risk Scores, Medical Scientist Training Program
OpenAlex ID: W4379056255