Gene polymorphisms in the ornithine decarboxylase–polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations

Abstract

Background The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. Methods Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. Results In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 123Gastric Cancer (2015) 18:495-503 DOI 10.1007 respectively; p interaction \ 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction \ 0.01). Conclusions Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Discriminating gastric cancer and gastric ulcer using human plasma amino acid metabolic profile

“…It has been found that elevated polyamine level is closely related to the increased GC risk . The ODC‐polyamine pathway may increase the growth of GC cells through controlling host DNA damage and immune reaction . It indicates that GC cells may use arginine–ornithine–polyamine pathway to synthesis polyamines to promote the proliferation of carcinoma cells.…”

“…Green blocks represent the five amino acids in the regression diagnosis model. immune reaction (42). It indicates that GC cells may use arginine-ornithine-polyamine pathway to synthesis polyamines to promote the proliferation of carcinoma cells.…”

miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells

“…As an endogenous ODC-activity antagonist, the antizyme 2 (OAZ2) expression is expected to be downregulated during cancer progression. Indeed, a dramatic decrease in the expression of OAZ2 has been reported in gastric cancer [ 51 ] and neuroblastoma [ 52 ], and high levels of OAZ2 expression are positively correlated with increased survival rate and favorable clinical prognosis. In this context, we reason that the chemosensitivity-promoting effects of OAZ2 may exhibit through antagonizing ODC activity.…”

Metabolism-associated genes in occurrence and development of gastrointestinal cancer: Latest progress and future prospect

“…Xiao et al [ 38 ] found that PYCR1, a key enzyme in intracellular proline synthesis, is highly expressed in GC, which induces cancer progression by increasing tumor proliferation and reaction to metabolic stress[ 38 ]. Another metabolic gene, known as the ODC1 , has been reported to contribute to the risk of GC by regulating the biosynthesis of ornithine decarboxylase polyamines or by the interaction between isoflavones and NQO1, OAZ2, and AMD1[ 39 ]. In summary, all these studies emphasize the tight connection between metabolic genes and the formation of GC, indicating that changes in specific metabolic pathways may influence the occurrence of GC.…”