Common genetic variants in prostate cancer risk prediction - results from the NCI breast and prostate cancer cohort consortium (BPC3)

Sara Lindstrom, Fredrick Schumacher, David Cox, Ruth C Travis, Demetrius Albanes, Naomi Allen, Gerald L Andriole, Sonja Berndt, Heiner Boeing, H Bas Bueno de Mesquita, E David Crawford, William Ryan Diver, John Michael Gaziano, Graham Giles, Edward Giovannucci, Carlos Gonzalez, Brian E Henderson, David J Hunter, Mattias Johansson, Laurence N KolonelJing Ma, Loic Le Marchand, Val eria Pala, Meir Stampfer, Daniel O Stram, Michael J Thun, Anne Tjonneland, Dimitrios Trichopoulos, Jarmo Virtamo, Stephanie Weinstein, Walter Churchill Willett, Meredith Yeager, Richard B Hayes, Gianluca Severi, Christopher A Haiman, Stephen Chanock, Peter Kraft

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)


Background: 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. Methods: 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. Results: 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). Conclusions: 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. Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.
Original languageEnglish
Pages (from-to)437 - 444
Number of pages8
JournalCancer Epidemiology, Biomarkers and Prevention
Issue number3
Publication statusPublished - 2012

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