Abstract
It is believed that an individual’s hereditary factors may be involved in the development of esophageal cancer (EC). The present study recruited 721 esophageal squamous cell carcinoma (ESCC) cases and 1208 controls and explored the roles of single nucleotide polymorphisms (SNPs) in the interleukin-4 (IL-4), IL-10, and herpesvirus entry mediator (HVEM) genes in contributing to ESCC risk. IL-4, IL-10, and HVEM SNPs were analyzed by employing an SNPscan method. After adjustment for body mass index (BMI), smoking, drinking, age and gender, we identified that the rs2070874 T>C locus in IL-4 gene decreased the risk of ESCC (CC vs. TT: P=0.008; CC vs. TT/TC: P=0.010). After a stratified analysis, we suggested that the IL-4 rs2070874 T>C variants might be a protective factor for ESCC in male, ≥63 years old, never smoking, drinking and BMI < 24 kg/m2 subgroups. In addition, we identified that the rs2243263 G>C polymorphism in IL-4 gene was a risk factor for ESCC development in the BMI ≥ 24 kg/m2 subgroup (GC vs. GG: P=0.030 and GC/CC vs. GG: P=0.018). We identified an association of the IL-4 rs2070874 T>C SNP with the decreased susceptibility of ESCC in stage I/II subgroup. Finally, we found an association of the IL-10 rs1800872 T>G SNP with a worse differentiation (TG vs. TT: P=0.048 and GG/TG vs. TT: P=0.032). In conclusion, the findings indicate a potential importance of IL-4 rs2070874 T>C, IL-4 rs2243263 G>C and IL-10 rs1800872 T>G SNPs in the development of ESCC.
Highlights
In China, esophageal cancer (EC) is the fourth most frequently diagnosed form of malignant tumor in males and the fifth most commonly diagnosed form in females, approximately 320800 and 157200 cases occurred in 2015, respectively [1]
Some studies indicated that the single nucleotide polymorphism (SNP) in inflammation and immune-related genes might influence the risk of EC [40,41]
We explored the role of immune-related gene SNPs (HVEM rs2234167, IL-4 rs2070874, and rs2243263, and IL-10 rs1800896 and rs1800872) to Esophageal squamous cell carcinoma (ESCC) development
Summary
In China, esophageal cancer (EC) is the fourth most frequently diagnosed form of malignant tumor in males and the fifth most commonly diagnosed form in females, approximately 320800 and 157200 cases occurred in 2015, respectively [1]. Esophageal squamous cell carcinoma (ESCC) is a major histological subtype, accounting for 90% of all EC cases. The complex interaction of economical and environmental conditions with individual’s hereditary factors may lead to EC development [2,3]. The etiology and development of EC is not fully understood, despite many investigations have payed close attention to the importance of immunity [4,5]. It was hypothesized that some important variants in immune-related genes may influence the susceptibility of ESCC
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