title: Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.
abstract: METHODS
  To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer.
  
  
  RESULTS
  The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction)  < 0.05).
  
  
  CONCLUSIONS
  CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Yang
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Cho
authors.forename: Kwang-Pil
authors.initials: KP
authors.lastname: Ko
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Ma
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Bo Youl
authors.initials: BY
authors.lastname: Choi
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Soung-Hoon
authors.initials: SH
authors.lastname: Chang
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D044466:Asian People / Q000235:genetics; D016203:CDC2 Protein Kinase / Q000235:genetics; D016022:Case-Control Studies; D060754:Equol / Q000097:blood / Q000494:pharmacology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D019833:Genistein / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000097:blood / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D048789:Phytoestrogens / Q000097:blood / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D056910:Republic of Korea; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D019014:fas Receptor / Q000235:genetics
chemical_list: D016588:Anticarcinogenic Agents; C491901:FAS protein, human; D007529:Isoflavones; D017705:Lignans; D048789:Phytoestrogens; D019014:fas Receptor; D060754:Equol; C004742:daidzein; D019833:Genistein; D051057:Proto-Oncogene Proteins c-akt; D016203:CDC2 Protein Kinase; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone