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

Title
Gene polymorphisms in the ornithine decarboxylase–polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations
Author
최보율
Keywords
Gastric cancer; Ornithine decarboxylase; SNPs; Phytoestrogen; Polyamine; NQO1; OAZ2; AMD1
Issue Date
2014-07
Publisher
Springer
Citation
Gastric Cancer, 2014, 18(3), P.495-503
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 (95 % CI 0.70?0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15?0.90) and OR 0.26 (95 % CI 0.10?0.64), 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.
URI
https://link.springer.com/article/10.1007/s10120-014-0396-5http://hdl.handle.net/20.500.11754/47067
ISSN
1436-3291; 1436-3305
DOI
10.1007/s10120-014-0396-5
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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