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

• Published in: Molecular nutrition & food research Vol. 56; no. 11; pp. 1617 - 1626
• Main Authors: Yang, Jae Jeong, Cho, Lisa Y., Ko, Kwang-Pil, Ma, Seung Hyun, Shin, Aesun, Choi, Bo Youl, Han, Dong Soo, Song, Kyu Sang, Kim, Yong Sung, Chang, Soung-Hoon, Shin, Hai-Rim, Kang, Daehee, Yoo, Keun-Young, Park, Sue K.
• Format: Journal Article
• Language: English
• Published: Weinheim Blackwell Publishing Ltd 01.11.2012; Wiley
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - pharmacology; Aged; AKT/NF-κB signaling; Anticarcinogenic Agents - pharmacology; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Case-Control Studies; CDC2 Protein Kinase - genetics; CDK1; Enterolactone; Equol - blood; Equol - pharmacology; FAS; fas Receptor - genetics; Female; Food industries; Fundamental and applied biological sciences. Psychology; Gene-Environment Interaction; Genetic Predisposition to Disease; Genistein - blood; Genistein - pharmacology; Humans; Isoflavones - blood; Isoflavones - pharmacology; Lignans - pharmacology; Male; MAP Kinase Kinase Kinase 1 - genetics; MAP3K1; Middle Aged; Odds Ratio; Phytoestrogens - blood; Phytoestrogens - pharmacology; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Republic of Korea; Signal Transduction - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - prevention & control; B signaling; MAP3K1; Enterolactone; Interaction; Malignant tumor; Carcinogenesis; AKT/NF; Case study; Phytoestrogen; Gene; CDK1; FAS; Cancer
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201200169

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.