Prediction of survival in patients with metastatic prostate cancer by single nucleotide polymorphisms of cancer-associated genes.

Abstract

177 Background: Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. Methods: A total of 185 PCa patients with bone metastasis at initial diagnosis were analyzed. Each patient was genotyped using a Cancer SNP panel that contained 1421 SNPs in 408 cancer-related genes. SNPs associated with the survival were screened by log rank test. A prognostic scoring index using selected SNPs was developed by incorporating the difference in their effect sizes to classify high-risk and low-risk groups and its predictive accuracy was assessed. Results: Fourteen SNPs in six genes, XRCC4, PSM1, GATA3, IL13, CASP8, and IGF1, were identified to have statistically significant association with the cancer-specific survival. The cancer-specific survivals of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 vs 2-3 vs 4-6 risk genotypes, P = 7.20×10−8). The predictive model using the 14 SNPs showed a statistically significant cross-validated accuracy in predicting the groups at high and low risk groups for poor survival (P = 0.0050). The high-risk group was independently associated with the survival in a multivariate analysis that included conventional clinicopathological variables (P = 0.0060). Conclusions: Using a panel of the SNPs, the prediction of the survival and optimization of the individualized treatment for patients with advanced PCa may be possible.