Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations

BACKGROUND: Both genetics and the environment are implicated as risk factors for prostate cancer (PCa). This population-based case-control study evaluated four single-nucleotide polymorphisms (SNPs) previously identified by genome-wide association studies to be associated with increased PCa susceptibility. Potential relationships between serum concentrations of phyto-estrogens and SNPs were also investigated. METHODS: Four SNPs (rs10993994, rs2660753, rs1016343 and rs6983267) were genotyped in 247 PCa patients, 125 BPH patients and 274 control men recruited in Scotland. Serum concentrations of the phyto-estrogens enterolactone, equol, genistein and daidzein were measured by isotope dilution gas chromatography-mass spectrometry. RESULTS: Increased PCa risk was associated with TT genotype of rs10993994 compared with CC and CT genotypes combined (odds ratio (OR) = 1.87; 95% confidence interval (CI), 1.26-2.77). TT homozygotes who had low serum enterolactone concentrations (below median) were more likely to have PCa (OR = 2.90; 95% CI, 1.28-6.57) than individuals with CC/CT genotype and high serum enterolactone concentrations (above median). PCa was not associated with the other three SNPs tested. CONCLUSIONS: PCa susceptibility was associated with TT genotype of SNP rs10993994 in this cohort of Scottish men and the increased risk of PCa was modified by serum enterolactone concentrations.