The expression of core 2 beta 1,6-N-acetylglucosaminyltransferase-1 (C2GnT) is associated with development and progression of malignancy. Sequence analysis showed that the codon 152 of C2GnT has a polymorphism having GTT encoding valine or ATT encoding isoleucine. By examining the polymorphism in prostate cancer and benign prostatic hyperplasia patients, we found that the C2GnT G allele was more frequently observed in the prostate cancer group (p = 0.015) than the control group. Men with the GG genotype had a 3.60-fold increased risk of prostate cancer, and men with the AG genotype had a 1.58-fold increased risk of prostate cancer compared with those with the AA genotype. The G allele was found to have a gene dosage effect for prostate cancer risk. No such risk was associated for benign prostatic hyperplasia. These results demonstrate that C2GnT A/G polymorphism is associated with the susceptibility to prostate cancer in a Japanese population. (c) 2005 Elsevier Inc. All rights reserved.