Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism-related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA ( IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43-0.98, P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41-0.93, P = 0.021 and IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47-0.93, P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48-0.95, P = 0.026). However, we also found that IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02-3.46, P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06-3.47, P = 0.032). This study suggests that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA. © 2018 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.