Cumulative evidence for association between genetic polymorphisms and esophageal cancer susceptibility: A review with evidence from meta-analysis and genome-wide association studies.

Jie Tian,Chunjian Zuo,Caiyang Liu,Guanchu Liu,Huanwen Chen

doi:10.1002/cam4.1972

Abstract

An increasing number of publications had reported the association between single‐nucleotide polymorphisms (SNPs) and esophageal cancer (EC) risk in the past decades. Results from these publications were controversial. We used PubMed, Medline, and Web of Science to identify meta‐analysis articles published before 30 July 2018, that summarize a comprehensive investigation for cumulative evidence of genetic polymorphisms of EC and its subtype risk. Two methods, Venice criteria and false‐positive report probability (FPRP) tests, were used to assess cumulative evidence of significant associations. At last, 107 meta‐analyses were considered to be in conformity with the inclusion criteria, yielding 51 variants associated with EC or esophageal squamous cell carcinoma (ESCC). Thirty‐eight variants were considered to be nominally significant associated with risk of EC or ESCC, whereas the rest showed non‐association. In additional, five variants on five genes were rated as strong cumulative epidemiological evidence for a nominally significant association with EC and ESCC risk, including CYP1A1 rs1048943, EGF rs444903, HOTAIR rs920778, MMP2 rs243865, and PLCE1 rs2274223, 10 variants were rated as moderate, and 18 variants were rated as weak. Additionally, 17 SNPs were verified noteworthy in six genomewide association studies (GWAS) using FPRP methods. Collectively, this review offered a comprehensively referenced information with cumulative evidence of associations between genetic polymorphisms and EC and ESCC risk.

Highlights

This review collates a comprehensive investigation for cumulative evidence of genetic polymorphisms of Esophageal cancer (EC) and its subtype risk
We extracted relevant useful information from meta‐analyses and genomewide association studies (GWAS) to support a comprehensive assessment for further evaluation
CYP1A1, located on chromosome 15‐q22, is an isozyme of cytochrome P450 and encods aryl hydrocarbon hydroxylase (AHH) which may combine with DNA to form adducts via a series of biochemical reactions

Summary

| INTRODUCTION

Esophageal cancer (EC) is a digestive tract carcinoma and remains the sixth leading cause of a carcinoma‐associated. Barrett's esophagus and smoking tobacco have been verified as risk factors for EADC These environmental factors were considered to be risk factors for EC, epidemiological and etiological studies have shown that the role of genetic variants was needed to be considered.[8]. GWAS that have two stages (discovery and replication) have identified to be a commonly powerful and successful tool in the identification of genetic variants associated with susceptibility to complex human diseases or phenotypes.[20,21]. In 2010, of the 18 SNPs, Wang LD et al[24] summarized two identified susceptibility loci (10q23 and 20p13) associated with ESCC risk. More than 100 meta‐analyses and several GWAS with association between genetic variants and EC susceptibility had been performed, these results of different studies for same variant were inconsistent, indicating the possibility of false‐positive associations. We attempt to collect cumulative evidence of associations between genetic variants and EC risk from published meta‐analyses and GWAS, and evaluate these associations, which may offer referenced information for further investigation of genetic risk factors for EC and its subtype

| METHOD

| RESULTS

Findings

| DISCUSSION