Haplotypes, Loss of Heterozygosity, and Expression Levels of GlycineN-Methyltransferase in Prostate Cancer

methylation and interactingwith environmental carcinogens. In a previous study, we showed that GNMTacts as a susceptibility gene for hepatocellular carcinoma. Here, we report onour efforts to characterize the haplotypes, loss of heterozygosity (LOH), and expression levels of theGNMT in prostate cancer. Experimental Design: Peripheral blood mononuclear cell DNA collected from 326 prostate cancer patients and 327 age-matched controls was used to determine GNMT haplotypes. Luciferase reporter constructs were used to compare the promoter activity of different GNMT haplotypes. GNMT LOH rates in tumorous specimens were investigated via a comparison with peripheral blood mononuclear cell genotypes. Immunohistochemical staining was used to analyze GNMTexpression in tissue specimens collected from 5 normal individuals, 33 benign prostatic hyperplasia patients, and 45 prostate cancer patients. Results: Three major GNMT haplotypes were identified in 92 % of the participants: A, 16GAs/ DEL/C (58%); B,10GAs/INS/C (19.9%); and C,10GAs/INS/T (14.5%). Haplotype C carriers had significantly lower risk for prostate cancer compared with individuals with haplotype A (odds ratio, 0.68; 95 % confidence interval, 0.48-0.95). Results from a phenotypic analysis showed tha