Role of polymorphisms of the IGF2 and IGFBP3 genes and risk of gastric carcinoma in China.
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 (CIs) 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% CI = 1.28-2.08, P < 0.05; OR = 1.46, 95% CI = 1.11-1.98, P < 0.05; OR = 1.53, 95% CI = 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 together, a greater effect on GC risk is observed.
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Jun
J
Gu
Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Maolan
M
Li
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Ping
P
Dong
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Jianhua
J
Lu
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Zhujun
Z
Tan
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Xiangsong
X
Wu
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Jiasheng
J
Mu
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Lin
L
Zhang
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Wenguang
W
Wu
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Qichen
Q
Ding
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Jiahua
J
Yang
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Yang
Y
Cao
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Qian
Q
Ding
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
Hao
H
Weng
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China. Email: liuybphd@126.com.
Yingbin
Y
Liu
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
D018972:Insulin-Like Growth Factor Binding Protein 3; D007335:Insulin-Like Growth Factor II