The role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese population.
Insulin-like growth factors (IGFs) and their receptors play a crucial role in regulating cell proliferation, differentiation, and apoptosis. Insulin-like growth factor-binding protein-3 is the most abundant insulin-like growth factor receptor in the serum and binds the majority of insulin-like growth factors. Studies reported that circulating level of insulin-like growth factor-binding protein-3 was modulated by functional genetic variants of insulin-like growth factor-binding protein-3 and, therefore, maybe associated with the risk of gastric cancer. In this case-control study of 576 gastric cancer cases and 647 cancer-free control participants in a high-risk Chinese population, we tested the hypothesis that functional polymorphisms A-202C and Gly32Ala of insulinlike growth factor-binding protein-3 are associated with risk of gastric cancer. We found that the variant 32Ala allele was associated with a significantly increased risk of gastric cancer (adjusted odds ratio=1.84, 95% confidence interval=1.45-2.33 for 32Gly/Ala and odds ratio=2.39, 95% confidence interval=1.47-3.90 for 32Ala/Ala, respectively), compared with the wild-type homozygote 32Gly/Gly. Although the A-202C variant was not significantly associated with gastric cancer risk in the single locus analysis, we found a significant locus-locus interaction between insulin-like growth factor-binding protein-3 A-202C and Gly32Ala loci on gastric cancer risk (Pint<0.001). These findings suggest that functional variants of insulin-like growth factor-binding protein-3 might be important markers for gastric cancer susceptibility and further studies are warranted to characterize the functional relevance of the locus-locus interaction of this gene.
Chen
Wensen
W
Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing, China.
Wang
Lina
L
Ke
Qiao
Q
Jin
Guangfu
G
Tan
Yongfei
Y
Zhou
Yan
Y
Hu
Zhibin
Z
Ma
Hongxia
H
Wang
Jianmin
J
Hua
Zhaolai
Z
Ding
Weiliang
W
Shen
Jing
J
Xu
Yaochu
Y
Shen
Hongbing
H
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins