Common genetic variants in prostate cancer risk prediction - results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3) - Abstract

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 SNP 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 NCI 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 PSA screening. Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.

Written by:
Lindstr√∂m S, Schumacher F, Cox DG, Travis RC, Albanes D, Allen NE, Andriole GL, Berndt SI, Boeing H, Bueno-de-Mesquita HB, Crawford D, Diver WR, Gaziano JM, Giles GG, Giovannucci EL, Gonzales C, Henderson B, Hunter DJ, Johansson M, Kolonel LN, Ma J, Le Marchand L, Pala V, Stampfer MJ, Stram DO, Thun M, Tjonneland A, Trichopoulos D, Virtamo J, Weinstein SJ, Willett WC, Yeager M, Hayes RB, Severi G, Haiman C, Chanock SJ, Kraft P.   Are you the author?
Department of Epidemiology, Harvard School of Public Health, Building II, 1st Floor, 665 Huntington Avenue, Boston, MA, 02115, United States.

Reference: Cancer Epidemiol Biomarkers Prev. 2012 Jan 11. Epub ahead of print.
doi: 10.1158/1055-9965.EPI-11-1038

PubMed Abstract
PMID: 22237985 Prostate Cancer Section