Genetic Analysis Reveals a Significant Contribution of CES1 to Prostate Cancer Progression in Taiwanese Men

The genes that influence prostate cancer progression remain largely unknown. Since the carboxylesterase gene family plays a crucial role in xenobiotic metabolism and lipid/cholesterol homeostasis, we hypothesize that genetic variants in carboxylesterase genes may influence clinical outcomes for prostate cancer patients. A total of 478 (36 genotyped and 442 imputed) single nucleotide polymorphisms (SNPs) in five genes of the carboxylesterase family were assessed in terms of their associations with biochemical recurrence (BCR)-free survival in 643 Taiwanese patients with prostate cancer who underwent radical prostatectomy. The strongest association signal was shown in ( = 9.64×10 for genotyped SNP rs8192935 and = 8.96 × 10 for imputed SNP rs8192950). After multiple test correction and adjustment for clinical covariates, rs8192935 ( = 9.67 × 10 ) and rs8192950 ( = 9.34 × 10 ) remained significant. These SNPs were correlated with expression levels, which in turn were associated with prostate cancer aggressiveness. Furthermore, our meta-analysis, including eight studies, indicated that a high expression predicted better outcomes among prostate cancer patients (hazard ratio 0.82, 95% confidence interval 0.70-0.97, = 0.02). In conclusion, our findings suggest that rs8192935 and rs8192950 are associated with BCR and that plays a tumor suppressive role in prostate cancer.