1. Why GWAS?

The etiology of ESCC remains unclear, and epidemiological studies suggest that tobacco smoking, heavy alcohol drinking, micronutrient deficiency and dietary carcinogen exposure may cause this malignancy. However, only a portion of exposed individuals develop ESCC, indicating that individual’s genetic makeup may also play an important role in esophageal carcinogenesis. GWAS is a powerful method in interrogation of genome-wide variants associated with complex human diseases and many genetic susceptibility loci for various types of human cancer have been identified with this approach.

2. Why Survival GWAS?

Although surgery, chemotherapy and radiotherapy are frequently used to treat ESCC, the long-term outcome of this cancer is still dismal, with 5-year survival rates around 30%. It has been observed that some demographic and clinicopathological characteristics of patients, such as age, sex, history of alcohol consumption and tobacco smoking, tumor stage and lymph node metastasis, have an impact to some extent on length of survival in ESCC. Nevertheless, these clinical and lifestyle features can only partially explain the great heterogeneity in survival times for affected individuals. Studies have suggested that germline genetic variability can provide important prognostic information for those with cancer.

3. Why eQTL?

eQTLs are regions of the genome containing SNPs that influence the expression level of one or more genes. They help researchers to understand why risk variants susceptible to certain disease. The mapping and positional cloning of an eQTL may reveal an expression regulator such as a transcription factor or small regulatory RNA. Besides, studies have shown that genetic variants reproducibly associated with complex diseases or phenotypes are found to be significantly enriched for eQTLs. Therefore, eQTL analysis is a good way to figure out the gene regulatory networks behind phenotypes, providing important insights into the underlying genetic mechanism of complex traits.

4. Why Associations of Somatic Mutations with Survival of ESCC Patients?

There are currently no specific molecule-targeting agents for ESCC treatment. Several studies on WES or WGS of ESCC in Chinese populations and Japanese populations have been published recently. These studies reported an extremely high frequency of TP53 mutations and low prevalence but statistically significant SNVs in several other genes including CDKN2A, NOTCH1, RB1 and PIK3CA. We have comprehensively characterized the genomic landscape features in ESCC that may identify potential targets that may guide to develop precision treatment and prevention of this malignancy. However, the associations between somatic mutation (SNVs/indels) and patients’ survival have not been systematically explored yet.

5. What version of dbSNP is CCGD-ESCC querying?

CCGD-ESCC is currently querying build 146 of dbSNP.

6. What version of the human genome sequence are the data mapped to at CCGD-ESCC?

All data in CCGD-ESCC is currently mapped to hg19.