Clinical utility of five genetic variants for predicting prostate cancer risk and mortality
Article first published online: 3 DEC 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 69, Issue 4, pages 363–372, 1 March 2009
How to Cite
Salinas, C. A., Koopmeiners, J. S., Kwon, E. M., FitzGerald, L., Lin, D. W., Ostrander, E. A., Feng, Z. and Stanford, J. L. (2009), Clinical utility of five genetic variants for predicting prostate cancer risk and mortality. Prostate, 69: 363–372. doi: 10.1002/pros.20887
- Issue published online: 22 JAN 2009
- Article first published online: 3 DEC 2008
- Manuscript Accepted: 9 OCT 2008
- Manuscript Received: 3 SEP 2008
- National Cancer Institute. Grant Numbers: RO1 CA56678, R01 CA092579, RO1 CA082664
- Pacific Northwest Cancer SPORE Program. Grant Number: P50 CA097186
- Department of Defense. Grant Number: PC061445
- Fred Hutchinson Cancer Research Center
- National Human Genome Research Institute
- prostate cancer;
A recent report suggests that the combination of five single-nucleotide polymorphisms (SNPs) at 8q24, 17q12, 17q24.3 and a family history of the disease may predict risk of prostate cancer. The present study tests the performance of these factors in prediction models for prostate cancer risk and prostate cancer-specific mortality.
SNPs were genotyped in population-based samples from Caucasians in King County, Washington. Incident cases (n = 1,308), aged 35–74, were compared to age-matched controls (n = 1,266) using logistic regression to estimate odds ratios (OR) associated with genotypes and family history. Cox proportional hazards models estimated hazard ratios for prostate cancer-specific mortality according to genotypes.
The combination of SNP genotypes and family history was significantly associated with prostate cancer risk (ptrend = 1.5 × 10−20). Men with ≥5 risk factors had an OR of 4.9 (95% CI 1.6–18.5) compared to men with none. However, this combination of factors did not improve the ROC curve after accounting for known risk predictors (i.e., age, serum PSA, family history). Neither the individual nor combined risk factors was associated with prostate cancer-specific mortality.
Genotypes for five SNPs plus family history are associated with a significant elevation in risk for prostate cancer and may explain up to 45% of prostate cancer in our population. However, they do not improve prediction models for assessing who is at risk of getting or dying from the disease, once known risk or prognostic factors are taken into account. Thus, this SNP panel may have limited clinical utility. Prostate 69:363–372, 2009. © 2008 Wiley-Liss, Inc.