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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

Authors

  • Jae Jeong Yang,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Lisa Y. Cho,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Kwang-Pil Ko,

    1. Department of Preventive Medicine, Gachon University of Medicine and Science, Incheon, Korea
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  • Seung Hyun Ma,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Aesun Shin,

    1. Molecular Epidemiology Branch, Research Institute, National Cancer Center, Goyang, Korea
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  • Bo Youl Choi,

    1. Department of Preventive medicine, Hanyang University College of Medicine, Seoul, Korea
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  • Dong Soo Han,

    1. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
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  • Kyu Sang Song,

    1. Department of Pathology, Chungnam National University College of Medicine, Daejeon, Korea
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  • Yong Sung Kim,

    1. Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
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  • Soung-Hoon Chang,

    1. Department of Preventive Medicine, Konkuk University, Chungju, Korea
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  • Hai-Rim Shin,

    1. Department of Preventive Medicine, Gachon University of Medicine and Science, Incheon, Korea
    2. Non Communicable Diseases and Health Promotion, World Health Organization, Western Pacific Regional Office, Manila, Philippines
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  • Daehee Kang,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
    3. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
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  • Keun-Young Yoo,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
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  • Sue K. Park

    Corresponding author
    1. Cancer Research Institute, Seoul National University, Seoul, Korea
    2. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
    • Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
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Correspondence: Dr. Sue K. Park, Department of Preventive Medicine, Seoul National University College of Medicine, 103 Yongon (Daehangno), Jongno-gu, Seoul, Korea

E-mail: suepark@snu.ac.kr

Fax: +82-2-747-4830

Abstract

Scope

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.

Methods and 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 (pinteraction < 0.05).

Conclusion

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.

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