Abstract 1285: Analysis of esophageal cancer SNPs and gene expression to predict ESCC risk

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Abstract Esophageal cancer is one of most common cancers worldwide and its incidence has increased rapidly over the past decades. The majority of esophageal cancers is the esophageal squamous cell carcinoma (ESCC), which is particularly prevalent in Asian and South African areas. Most cases of ESCC are diagnosed at advanced stages, with an overall 5-year survival rate of 10–20%. Currently, genome-wide association studies (GWAS) are used to identify high risk individuals for the development of ESCC. Many SNPs have been identified to associate with a risk of ESCC. However, the effect size attributable to individual SNPs was typically modest, suggesting that genetic variants may only account for a very small amount of genetic risk and heritability of ESCC. The combined effect of multi genetic variants with altered mRNA expression play critical roles in ESCC. In this study, we used several existing bioinformatics databases (HaploReg, GTEx Portal and cBio Portal). We first selected 450 potential ESCC risk SNPs from HaploReg and then defined which SNPs caused gene expression alterations in the esophagus through expression quantitative trait loci (eQTL). Nine SNPs in eight genes (MUC1, ALS2CR12, ADHB1, TMEM173, XBP1, PLCE1, HEATR3 and SMG6) were identified as having altered mRNA expression. The altered mRNA expression of these seventeen genes are: MUC1, THBS3, GBAP1, EFNA1, SCAMP3, CASP8, CASP10, ALS2CR12, STRADB, ADH4, TMEM173, CYCTM1, DNAJC18, DNAJC20, NOC3L, HEATR3 and SRR. These altered gene expressions in the mucosal layer of the esophagus metabolize enzymes, repair DNA, and prevent cell death and inflammation, all of which may indicate that the existing altered esophageal mRNA levels plus the predisposition of normal esophageal epithelial cells can lead to harmful environmental carcinogens, thus attributing to ESCC development. In order to validate these gene alterations related to ESCC SNPs in screening and early detection of high risk individuals, DNA genotyping of this group of SNPs with a prospective cohort (n=5451) in a high risk area of ESCC will be tested in future studies. Citation Format: Lilly A. Ding, Molly P. Ding, Xin Song, Lidong Wang, Liang Wang. Analysis of esophageal cancer SNPs and gene expression to predict ESCC risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1285. doi:10.1158/1538-7445.AM2017-1285