Dataset Information

Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival.

ABSTRACT: 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.

SUBMITTER: Xu L

PROVIDER: S-EPMC4487138 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival.

Xu Linping L Long Jianping J Wang Peng P Liu Kangdong K Mai Ling L Guo Yongjun Y

Oncology letters 20150512 1

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 ...[more]

PMID: 26171056

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Project description:BackgroundTraditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival.MethodsWe evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided.ResultsIn the hypothesis-generating dataset, SNP rs4778137 (C>G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)).ConclusionThe rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.

Dataset Information

Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival.

Publications

Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival.

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