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

Abstract

BACKGROUND: Both genetics and the environment are implicated as risk factors for prostate cancer (PCa). This populationbased 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) ¼ 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 ¼ 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.

Association between 8q24 rs6983267 polymorphism and cancer susceptibility: a meta-analysis involving 170,737 subjects

“…However, our outcomes were different to the results shown by Ho et al . [ 73 ], which demonstrated that rs6983267 polymorphism was not associated with prostate cancer. This discrepancy may be caused by the limited sample size.…”

“…Ho et al . [ 73 ] included only 521 subjects (247 cases and 274 controls), which may lack sufficient power to support or deny an association. Previous meta-analyses also focused on the relationship between the rs6983267 and prostate cancer.…”

MSMB gene rs10993994 polymorphism increases the risk of prostate cancer

“…Among these single nucleotide polymorphisms (SNPs), several genome-wide association studies (GWASs) identified rs10993994 polymorphism in the promoter region of MSMB gene [7, 8], which was significantly associated with PC susceptibility. Subsequent studies [9–18] also investigated the association between MSMB gene rs10993994 polymorphism and PC susceptibility, but with conflicting conclusions. These studies were conflicting and inconclusive probably due to different ethnic populations, clinical heterogeneity, and small sample sizes.…”

The rs10993994 in the proximal MSMB promoter region is a functional polymorphism in Asian Indian subjects

“…Till date, there have been 30 SNPs reported in the dbSNP ( http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref ) corresponding to the MSMB proximal promoter region of which rs10993994 is well established as a susceptibility locus for PCa. However, there are few reports which suggest that this SNP has not been found to be a predisposing factor for benign prostatic hyperplasia (BPH) development (Ho et al 2012 ; Ban and Yoo 2014 ). Further, the MSMB promoter region has recently been studied extensively; using in vitro analysis and a ~370 bp region has been shown to harbour the core promoter and two negative regulatory elements.…”