title: 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 (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.
authors: Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehakno, Jongno-Gu, Seoul, 110-799, Republic of Korea, lisaycho@snu.ac.kr.
authors: Lisa Y
authors: LY
authors: Cho
authors: Jae Jeong
authors: JJ
authors: Yang
authors: Kwang-Pil
authors: KP
authors: Ko
authors: Seung Hyun
authors: SH
authors: Ma
authors: Aesun
authors: A
authors: Shin
authors: Bo Youl
authors: BY
authors: Choi
authors: Hyun Ja
authors: HJ
authors: Kim
authors: Dong Soo
authors: DS
authors: Han
authors: Kyu Sang
authors: KS
authors: Song
authors: Yong Sung
authors: YS
authors: Kim
authors: Soung-Hoon
authors: SH
authors: Chang
authors: Hai-Rim
authors: HR
authors: Shin
authors: Daehee
authors: D
authors: Kang
authors: Keun-Young
authors: KY
authors: Yoo
authors: Sue K
authors: SK
authors: Park
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000097:blood; D012437:Adenosylmethionine Decarboxylase / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D060754:Equol / Q000097:blood; D059647:Gene-Environment Interaction; D019833:Genistein / Q000097:blood; D006801:Humans; D007529:Isoflavones / Q000097:blood; D017705:Lignans / Q000097:blood; D015337:Multicenter Studies as Topic; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D048789:Phytoestrogens / Q000097:blood*; D011073:Polyamines / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D007529:Isoflavones; D017705:Lignans; D048789:Phytoestrogens; D011073:Polyamines; D060754:Equol; C004742:daidzein; D019833:Genistein; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D009955:Ornithine Decarboxylase; C000608756:AMD1 protein, human; D012437:Adenosylmethionine Decarboxylase; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone