Methyl group metabolism gene polymorphisms and susceptibility to prostaticcarcinoma

BACKGROUND. Alterations of DNA methylation are very frequent in prostatic c arcinoma. A possible cause underlying altered DNA methylation could be an i nsufficient level of S-adenosylmethionine as a consequence of nutritional i mbalances or of weaker alleles of genes for its synthesis, i.e., encoding m ethylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and beta -cystathione synthetase (CBS). Therefore, homozygosity or heterozygosi ty for such weaker alleles may underlie susceptibility to prostatic carcino ma. METHODS. The distribution of the two most frequent MTHFR, MS, and CBS allel es was determined in 132 prostatic carcinoma patients and 150 population co ntrols by restriction fragment length polymorphism-(RFLP) PCR. RESULTS. In the controls, a Hardy-Weinberg equilibrium was observed for eac h allele pair. No significant differences were observed with respect to age or gender. No significant differences for single genes or combinations wer e found between prostatic carcinoma patients and controls, although the MTH FR Val allele was slightly overrepresented among the tumor patients. Neithe r did the allele distribution significantly differ among the prostatic carc inoma patients stratified according to age, clinical stage, or presence of metastases. However, the MTHFR Val allele tended to be associated with high er tumor grade. CONCLUSIONS. In general, the data do not support the hypothesis that weaker alleles in methyl group metabolism genes constitute a major factor in the high prevalence of DNA methylation alterations found in prostatic carcinoma . However, a potential association with the MTHFR genotype deserves further study. Prostate 45:225-231, 2000. (C) 2000 Wiley-Liss, Inc.