Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival

Xu, Lei; Long, Jian-Ping; Wang, Peng; Liu, Kangdong; Mai, Linh; Guo, Yongjun

doi:10.3892/ol.2015.3201

Cited by 10 publications

(8 citation statements)

References 27 publications

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“…The induction of ODC1 might contribute to increased cellular proliferation rates, which in turn predisposes to, and possibly potentiates, HCC. Moreover, ODC1 is overexpressed in several human cancers such as colon, liver [84], and breast carcinomas [85]. A similar role can be hypothesized for ARAF; indeed, an overexpression of RAF kinases (i.e., ARAF, BRAF, and CRAF) is associated with activation of the ERK pathway, which in turn increases cell proliferation in vitro and in vivo [86].…”

Section: Cancermentioning

confidence: 77%

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Pauletto

Tolosi²,

Giantin³

et al. 2020

Toxins

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Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species.

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Section: Cancermentioning

confidence: 77%

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Pauletto

Tolosi²,

Giantin³

et al. 2020

Toxins

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“…increased ornithine levels can reduce ammonia and its associated oxidative stress via the urea cycle 19,20 , which may contribute to a protective mechanism as lower oxidative stress levels are associated with lower breast cancer risk 21 . However, ornithine is a substrate for producing polyamine via enzyme ornithine decarboxylase, which promotes the progression of cancer 5,11,22,23 . Although the biological mechanisms of action through which ornithine contributes to carcinogenesis are conflicting, the former mechanism may be dominant based on the findings from the present study.…”

Section: Discussionmentioning

confidence: 99%

Ornithine and breast cancer: a matched case–control study

Zhang

Tao

Chong

et al. 2020

Sci Rep

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In vivo and vitro evidence indicates that ornithine and its related metabolic products play a role in tumor development. Whether ornithine is associated with breast cancer in humans is still unclear. We examined the association between circulating ornithine levels and breast cancer in females. This 1:1 age-matched case–control study identified 735 female breast cancer cases and 735 female controls without breast cancer. All cases had a pathological test to ascertain a breast cancer diagnosis. The controls were ascertained using pathologic testing, clinical examinations, and/or other tests. Fasting blood samples were used to measure ornithine levels. The average age for cases and controls were 49.6 years (standard deviation [SD] 8.7 years) and 48.9 years (SD 8.7 years), respectively. Each SD increase in ornithine levels was associated with a 12% reduction of breast cancer risk (adjusted odds ratio [OR] 0.88; 95% confidence interval [CI] 0.79–0.97). The association between ornithine and breast cancer did not differ by pathological stages of diagnosis or tumor grades (all P for trend > 0.1). We observed no effect measure modification by molecular subtypes (P for interaction = 0.889). In conclusion, higher ornithine levels were associated with lower breast cancer risk in females.

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“…Earlier studies on breast and colorectal cancers reported that the G316A GG genotype is associated with a more favorable outcome than the AG/AA genotypes [ 18 , 19 ]. We investigated the association between SNP genotype and survival in a publicly available colorectal cancer cohort of 290 cases (Sieber, R2 Genomics Analysis and Visualization platform; , accessed on 3 August 2020).…”

Section: Resultsmentioning

confidence: 99%

“…Three possible genotypes result from the SNP: GG, AG and the variant AA which occurs at a low frequency of 7–10% in the general population [ 14 , 18 ]. A previous study has shown that the transcriptional repressor Mad1 suppresses the activity of the ODC1 promoter in colon cancer cells containing the A-allele but not the G-allele, and other studies have also reported that the E-box repressors MAD4 (MXD4) and MXI1 bind less strongly in cells homozygous for the GG genotype [ 18 , 19 ]. These findings suggest allele-specific regulation of ODC1 by E-box transcription factors.…”

Section: Introductionmentioning

confidence: 99%

“…These findings suggest allele-specific regulation of ODC1 by E-box transcription factors. It has also been shown that the GG genotype is associated with improved survival compared to people with AG/AA genotypes in colorectal and breast cancer patients [ 18 , 19 ]. This finding contrasts with those from a colon cancer prevention trial, in which individuals with the AA genotype who reported using aspirin were 10× less likely to have an adenoma recurrence compared to non-aspirin users with the GG genotype [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma

Gamble

Purgato

Henderson

et al. 2021

Cancers

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Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.

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Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival

Cited by 10 publications

References 27 publications

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Ornithine and breast cancer: a matched case–control study

A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma

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