In our study of men of European descent, GNMT STRP1 and rs10948059 were indeed associated with prostate cancer risk. Those with an increased number of tandem repeats had a 32% decreased risk of prostate cancer compared to those with less repeats. In addition, those with the rs10948059 T/T genotype had a 62% increased risk of prostate cancer compared to those with the C/C genotype This association appeared to be stronger in Ibufenac non-aggressive compared with aggressive cancers. These findings are in agreement with those of a recent study by Koutros et al., which showed a stronger association between serum sarcosine and non-aggressive prostate cancer, but no association with aggressive prostate cancer. It is therefore possible that GNMT may be a biomarker for early non-aggressive prostate cancer. Our study results are also supported by a study on the genotypic and phenotypic association of GNMT, which demonstrated that MLS1547 promoters containing either STRP1 10 GAs or rs10948059 T allele had significantly higher transcriptional activity than promoters containing STRP1 16 GAs or rs10948059 C allele. Although GNMT acts as a tumor suppressor and was found to be down-regulated in HCC, its role in the pathogenesis of prostate cancer remains unknown. Gnmt2/2 mice developed HCC but not prostate cancer, suggesting that other risk factors contributed to the tumorigenesis of prostate cancer besides deficiency or perturbation of the expression level of GNMT. Previously, we used a yeast two-hybrid system to screen proteins interacting with GNMT and found that DEPTOR and NPC2 bound directly with GNMT. We postulate that maybe GNMT exerts its function by interacting with other effectors including DEPTOR and NPC2. DEPTOR is an mTOR inhibitor reported to have an important and more direct role in prostate carcinogenesis. Therefore, further studies on the association of DEPTOR and NPC2 with prostate cancer are needed. Findings of this study are in contrast to those of our study in Taiwanese men, which showed that the rs10948059 T allele was not significantly associated with non-aggressive prostate cancer and had a protective association against aggressive prostate cancer.