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One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age.We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.

Original publication

DOI

10.1158/1055-9965.epi-11-1038

Type

Journal article

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Publication Date

03/2012

Volume

21

Pages

437 - 444

Addresses

Program in Molecular and Genetic Epidemiology,Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Keywords

Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Prostate-Specific Antigen, Prognosis, Discriminant Analysis, Models, Statistical, Risk Assessment, Risk Factors, Case-Control Studies, Cohort Studies, Follow-Up Studies, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, United States, Male, National Cancer Institute (U.S.), Early Detection of Cancer, Biomarkers, Tumor