Abstract
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.
Highlights
In the past few decades, the incidence of esophagogastric junction adenocarcinoma (EGJA) has been increasing worldwide.[1,2] According to its anatomical region relative to the esophagogastric junction (EGJ), EGJA has been divided into three subtypes by the Siewert classification
We found that rs1470579 A > C variant in the Insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) gene was a protective factor for EGJA (CC vs AA: crude odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44‐0.99, P = 0.045 and CC vs AA/AC: crude OR = 0.63, 95% CI = 0.42‐0.94, P = 0.023)
We explored the relationship of IGF2BP2 rs4402960 G > T, rs1470579 A > C, Insulin‐like growth factor‐1 (IGF1) rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A single nucleotide polymorphisms (SNPs) with the development of EGJA in 2261 subjects
Summary
In the past few decades, the incidence of esophagogastric junction adenocarcinoma (EGJA) has been increasing worldwide.[1,2] According to its anatomical region relative to the esophagogastric junction (EGJ), EGJA has been divided into three subtypes by the Siewert classification. Most of the IGF1 bind to insulin‐like growth factor binding proteins (IGFBPs). Some case‐control studies have focused on the relationship of IGFBP3 and IGF1 single nucleotide polymorphisms (SNPs) with the risk of cancer.[9-11]. A previous case‐control study indicated that IGFBP3 rs2270628 C > T was associated with an increased risk of ovarian cancer.[12]. Liu et al[14] reported that IGFBP3 rs2270628 C > T and rs3110697 G > A SNPs were associated with a significantly decreased risk of esophageal squamouscell carcinoma (ESCC). Some case‐control studies focused on the relationship of IGF1 SNPs and gastric cancer.[15,16]. Liu et al[24] found that IGF2BP2 variants might be an independent predictor of chemotherapeutic response in patients with metastatic gastric cancer. The associations of IGFBP3, IGF2BP2 and IGF1 SNPs with EGJA risk were unknown. With an aim to explore the relationship of IGF1, IGFBP3, and IGF2BP2 SNPs with the development of EGJA, IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci were selected and genotyped in 720 EGJA cases and 1541 controls
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