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
Article first published online: 5 OCT 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 11, pages 1617–1626, November 2012
How to Cite
Yang, J. J., Cho, L. Y., Ko, K.-P., Ma, S. H., Shin, A., Choi, B. Y., Han, D. S., Song, K. S., Kim, Y. S., Chang, S.-H., Shin, H.-R., Kang, D., Yoo, K.-Y. and Park, S. K. (2012), 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. Mol. Nutr. Food Res., 56: 1617–1626. doi: 10.1002/mnfr.201200169
- Issue published online: 24 OCT 2012
- Article first published online: 5 OCT 2012
- Manuscript Accepted: 9 AUG 2012
- Manuscript Revised: 9 JUL 2012
- Manuscript Received: 26 MAR 2012
- National Research Foundation of Korea
- Ministry of Education, Science and Technology. Grant Numbers: KRF-2007–313-E00175, 2011–0001564
- AKT/NF-κB signaling;
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).
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.