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Clinical utility of five genetic variants for predicting prostate cancer risk and mortality
Author(s) -
Salinas Claudia A.,
Koopmeiners Joseph S.,
Kwon Erika M.,
FitzGerald Liesel,
Lin Daniel W.,
Ostrander Elaine A.,
Feng Ziding,
Stanford Janet L.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20887
Subject(s) - prostate cancer , family history , medicine , single nucleotide polymorphism , oncology , proportional hazards model , odds ratio , population , cancer , hazard ratio , logistic regression , prostate , gynecology , genotype , biology , genetics , confidence interval , gene , environmental health
Abstract BACKGROUND 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. METHODS 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. RESULTS The combination of SNP genotypes and family history was significantly associated with prostate cancer risk (p trend = 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. CONCLUSION 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.