Abstract
Many molecular studies have indicated that genetic and epigenetic alterations are important for carcinogenesis in the prostate. Alterations in the one-carbon metabolism pathway can influence DNA synthesis and DNA methylation. Polymorphisms in the genes for the methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), serine hydroxymethyltransferase (SHMT) have been reported to be associated with some forms of malignancies. In a case-control study of 200 cases and 240 controls, we investigated whether four common polymorphisms in the MTHFR (C677T and A1298T), MTR (A2756G), SHMT1 (C1420T), MTRR (A66G), cystathione-\#946;-synthase (CBS, 844ins68), and reduced folate carrier (RFC-1, A80G) may have a role in altering prostate cancer susceptibility. The genotype was mainly determined by the PCR-RFLP method. The MTHFR C677T genotype was associated with a significant decrease in the risk with an adjusted odds ratio of 0.50 (95% confidence interval: 0.27-0.92). However, the MTHFR A1298C, MTR A2756G and SHMT1 C1420T, MTRR A66G, CBS and RFC-1 were not associated with prostate cancer risk. We also analyzed CpG island hypermethylation in five genes (GSTP1, RAR\#946;2, AR, DAPK, TIMP-3 and hMLH1) and its association with four polymorphisms in 50 prostate cancers. The MTHFR A1298C was significantly associated with AR methylation status. These findings suggest that polymorphisms of the MTHFR may be involved in carcinogenesis of the prostate.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2126.
Footnotes
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO
- American Association for Cancer Research
Volume 69, Issue 9 Supplement
