Research papers: Gastrointestinal CancerThe role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese populationChen, Wensena b; Wang, Linaa b; Ke, Qiaoa; Jin, Guangfua; Tan, Yongfeic; Zhou, Yanc; Hu, Zhibina; Ma, Hongxiaa; Wang, Jianmind; Hua, Zhaolaid; Ding, Weiliangc; Shen, Jinga; Xu, Yaochua; Shen, Hongbinga b Author Information aDepartment of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University bInstitute of Applied Toxicology, Nanjing Medical University, Nanjing 210029 cYixing People's Hospital, Yixing City, Jiangsu Province 214200 dYangzhong Cancer Institute, Yangzhong City, Jiangsu Province 210623, China Correspondence to Dr Hongbing Shen, Department of Epidemiology & Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Rd., Nanjing 210029, China Tel: +86 25 868 62756; fax: +86 25 868 62756; e-mail: [email protected] Received 24 October 2006 Accepted 27 December 2006 European Journal of Cancer Prevention: April 2008 - Volume 17 - Issue 2 - p 82-87 doi: 10.1097/CEJ.0b013e32809b4cff Buy Metrics Abstract 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. © 2008 Lippincott Williams & Wilkins, Inc.