These findings suggest that GNMT deficiency results in decreased ability in eradicating endogenous free radicals and xenobiotic compounds both at the cellular level and in an animal model; and therefore, homeostasis of GNMT expression is very important for the cellular defense against both endogenous and exogenous stress. However, the association of GNMT with prostate cancer in other races or ethnicities remains unclear. A recent study by Sreekumar et al. DMH2 reported that sarcosine �� a differential metabolite regulated by GNMT��CS1 increased markedly in tissue and serum of metastatic prostate cancer and was found in the urine after digital rectal examination in organ-confined disease. They showed a stepwise elevation of sarcosine tissue concentration during prostate cancer progression from benign prostate to clinically localized prostate cancer to metastatic disease. GNMT is the enzyme responsible for converting glycine to sarcosine, and they showed that knockdown of GNMT attenuated prostate cancer invasion. However, subsequent studies on the role of sarcosine as a potential biomarker for early prostate cancer detection failed to see any association between sarcosine concentration in the urine and either tumor grade or tumor stage, and studies on the association of serum sarcosine levels and prostate cancer reported conflicting results. The human GNMT gene is located at chromosome 6p12 and we previously reported that it has 3 polymorphic sites in the promoter region that may affect transcriptional activity: short tandem repeat 1, a n dinucleotide repeat polymorphism, INS/DEL with insertion or deletion of a GAGT tetranucleotide, and rs10948059. A recent study in Italians by Ianni et al. showed that the GNMT rs9462856 T allele, which is also located in the promoter region upstream of rs10948059, was associated with increased prostate cancer risk. Using the publicly available HapMap version 3, release R2 database, strong linkage disequilibrium was found between Ianni et al.��s rs9462856 and rs10948059. In this study, we tried to determine the association of the GNMT polymorphisms STRP1, INS/DEL and rs10948059 and prostate cancer risk in Americans of European ancestry.