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Title 

Genetic susceptibility on caga-interacting molecules and gene-environment interaction with phytoestrogens: A putative risk factor for gastric cancer

Authors 

J J YangL Y ChoK P KoA ShinS H MaB Y ChoiD S HanK S SongYong Sung KimJ Y LeeB G HanS H ChangH R ShinD KangK Y YooS K Park

Publisher 

Public Library of Science

Issue Date 

2012

Citation 

Plos One, vol. 7, no. 2, pp. e31020-e31020

Abstract 

Objectives: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. Methods: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens(genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. Results: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). Conclusions: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

ISSN 

1932-6203

Link 

http://dx.doi.org/10.1371/journal.pone.0031020

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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