The insulin-like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non-cancer control subjects were enrolled in this case-control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per-allele model after adjusting for other risk factors (OR: 1.14 [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also observed a positive and dosedependent association between the number of risk alleles and stomach cancer risk (P-trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted. (Cancer Sci 2011; 102: 2231-2235 S tomach cancer remains one of the most common cancers in Japan, as well as worldwide.(1) The known and suspected risk factors for stomach cancer include smoking, diabetes, family history of stomach cancer, green tea intake and Helicobacter pylori infection. Recent studies have focused on the detection of single nucleotide polymorphisms (SNP) that have an incident and prognostic impact in cancer, including stomach cancer. Specifically, SNP in the gene encoding insulin-like growth factor (IGF) have been studied in the context of several cancers, but to our knowledge, their influence in the development of stomach cancer has not yet been investigated.The IGF signaling system plays a central role in cellular growth, differentiation and proliferation.(2) IGF1 is reported to be a potential proliferative molecule, affecting almost every cell type via the RAS-mitogen-activated protein kinase signaling pathway. (3,4) It is also reported to be a powerful antiapoptotic molecule, activating the phosphatidylinositol-3 kinase-AKT pathway, which ultimately activates downstream transcription factors that regulate gene expression of proliferative, differentiation and antiapoptotic factors.(3,4) Given this role of IGF1 in stimulating cellular growth and inhibiting apoptosis, abnormalities in IGF1 levels might contribute to the development of cancer. IGF1 polymorphisms ...