AIM To assess the relationship between serum levels of insulin-like growth factor-1(IGF1)/IGF-binding protein-3(IGFBP3)and the risk of esophageal carcinoma.METHODS We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective,nested case-control study of participants from the Japan Collaborative Cohort Study.A baseline survey was conducted from 1988 to 1990.Of the 110585 enrolled participants,35%donated blood samples.Those who had been diagnosed with esophageal cancer were considered cases for nested case-control studies.A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels.RESULTS Thirty-one cases and 86 controls were eligible for the present assessment.The molar ratio of IGF1/IGFBP3,which represents the free and active form of IGF1,was not correlated with the risk of esophageal carcinoma.A higher molar difference between IGFBP3and IGF1,which estimates the free form of IGFBP3,was associated with a decreased risk of esophageal carcinoma(P=0.0146),and people in the highest tertile had the lowest risk(OR=0.107,95%CI:0.017-0.669).After adjustment for body mass index,tobacco use,and alcohol intake,the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma(P=0.0150).CONCLUSION The free form of IGFBP3,which is estimated by this molar difference,may be inversely associated with esophageal cancer incidence. AIM To assess the relationship between serum levels of insulin-like growth factor-1 (IGF1) / IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma. METHODS We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% of donated blood samples. who had been diagnosed with esophageal cancer were considered cases for nested case-control studies. A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels. . The molar ratio of IGF1 / IGFBP3, which represents the free and active form of IGF1, was not correlated with the risk of esophageal carcinoma. A higher molar difference between IGFBP3 and I GF1, which estimates the free form of IGFBP3, was associated with a decreased risk of esophageal carcinoma (P = 0.0146), and people in the highest tertile had the lowest risk (OR = 0.107, 95% CI: 0.017-0.669) adjustment for body mass index, tobacco use, and alcohol intake, the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma (P = 0.0150) .CONCLUSION The free form of IGFBP3, which is estimated by this molar difference, may be inversely associated with esophageal cancer incidence.