Background The insulin-like growth factor signaling pathway plays an important role in the modulation of cell growth and proliferation.The aim of this study was to investigate the role of polymorphisms of the insulin-...Background The insulin-like growth factor signaling pathway plays an important role in the modulation of cell growth and proliferation.The aim of this study was to investigate the role of polymorphisms of the insulin-like growth factor 2 （IGF2） and IGF-binding protein 3 （IGFBP3） genes,which encode key proteins of this pathway,as risk factors for gastric carcinoma （GC）.Methods A case-control study including 404 histologically confirmed GC patients and 424 healthy controls of the same ethnicity was conducted to retrospectively investigate the genetic polymorphisms of two genes,IGF2＋820A＞G （rs680） and IGFBP3 A-202C （rs2854744）.Adjusted odds ratios （ORs） and 95％ confidence intervals （C/s） were calculated using Logistic regression.Results The IGF2 genetic variants examined contributed to GC risk individually （OR,1.26; 95％ CI,1.08-1.46）.The genotype frequencies of IGFBP3 A-202C were not significantly different between the cancer cases and controls （P ＞0.05）.Compared to the IGF2 AA genotype,carriers of one variant combined genotype were more pronounced among young subjects （＜60 years）,male subjects,never smokers,and those with a family history of cancer （OR=1.36,95％ CI=1.09-1.72,P ＜0.05; OR=1.61,95％ C/=1.28-2.08,P ＜0.05; OR=1.46,95％ C/=1.11-1.98,P ＜0.05; OR=1.53,95％ C/=0.91-2.6,P ＜0.05; respectively）.Moreover,when the combined effects of the risk genotypes were investigated,significant associations were detected between highrisk genotypes in IGF2 and IGFBP3 （OR,2.47; 95％ CI,1.75-3.49）.Conclusions Our results suggest that polymorphic variants of the IGF2 genes modulate gastric carcinogenesis.Moreover.when the IGF2 and IGFBP3 variants are evaluated toaether,a areater effect on GC risk is observed.展开更多
基金This work was supported by Shanghai Committee of Science and Technology （No.12JC1406700,12410705900,12401905800）,the Foundation of Xinhua Hospital （No.12YJ01）,the National Natural Science Foundation of China （No.30972918,81172029,81272402）,the National High Technology Research and Development Program （863 Program） （No.2012AA022606）,and the Medical and Engineering Cross-Foundation of Shanghai Jiaotong University （No.YG2011ZD07）.
文摘Background The insulin-like growth factor signaling pathway plays an important role in the modulation of cell growth and proliferation.The aim of this study was to investigate the role of polymorphisms of the insulin-like growth factor 2 （IGF2） and IGF-binding protein 3 （IGFBP3） genes,which encode key proteins of this pathway,as risk factors for gastric carcinoma （GC）.Methods A case-control study including 404 histologically confirmed GC patients and 424 healthy controls of the same ethnicity was conducted to retrospectively investigate the genetic polymorphisms of two genes,IGF2＋820A＞G （rs680） and IGFBP3 A-202C （rs2854744）.Adjusted odds ratios （ORs） and 95％ confidence intervals （C/s） were calculated using Logistic regression.Results The IGF2 genetic variants examined contributed to GC risk individually （OR,1.26; 95％ CI,1.08-1.46）.The genotype frequencies of IGFBP3 A-202C were not significantly different between the cancer cases and controls （P ＞0.05）.Compared to the IGF2 AA genotype,carriers of one variant combined genotype were more pronounced among young subjects （＜60 years）,male subjects,never smokers,and those with a family history of cancer （OR=1.36,95％ CI=1.09-1.72,P ＜0.05; OR=1.61,95％ C/=1.28-2.08,P ＜0.05; OR=1.46,95％ C/=1.11-1.98,P ＜0.05; OR=1.53,95％ C/=0.91-2.6,P ＜0.05; respectively）.Moreover,when the combined effects of the risk genotypes were investigated,significant associations were detected between highrisk genotypes in IGF2 and IGFBP3 （OR,2.47; 95％ CI,1.75-3.49）.Conclusions Our results suggest that polymorphic variants of the IGF2 genes modulate gastric carcinogenesis.Moreover.when the IGF2 and IGFBP3 variants are evaluated toaether,a areater effect on GC risk is observed.
