Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival

Ornithine decarboxylase (ODC) is a significant rate-limiting enzyme in polyamine synthesis, required for normal cell growth, and is highly expressed in various malignancies, including colorectal and breast cancer. In the present study, the associations between the ODC G316A single nucleotide polymorphism (SNP) and breast cancer-specific survival were investigated. In addition, the functional effects of this SNP were examined in the MCF-7 human breast cancer cell line. The present study recruited 300 stage I-III breast cancer cases, which were diagnosed at the Affiliated Cancer Hospital of Zhengzhou University (Zhengzhou, China) between 2002 and 2003, with follow-up visits conducted until May 2013. ODC G316A was genotyped (ODC GG vs. ODC AG/AA) in the 300 cases and the association of the genotypes with cancer-specific survival was analyzed. In the MCF-7 cell line, the ODC allele-specific binding of E-box transcription factors was determined using western blot and chromatin immunoprecipitation assays. Survival differences were observed between the two genotypes: Compared with the ODC GG genotype, patients with ODC GA/AA exhibited significantly higher survival rates (P<0.05). In cultured cells, the ODC SNP, which is flanked by two E-boxes, appeared to predict ODC promoter activity. Furthermore, the E-box activator c-MYC and repressor MAX interactor 1 were found to preferentially bind to ODC minor A-alleles compared with major G-alleles, in cultured MCF-7 cells. In conclusion, the results of the current study suggest that the regulation of ODC may affect survival in breast cancer patients and indicate a model in which the ODC SNP may be protective for breast adenoma recurrence and detrimental for survival following a diagnosis of breast cancer.