PADI4 rs2240337 G>A polymorphism is associated with susceptibility of esophageal squamous cell carcinoma in a Chinese population.

Liming Wang,Yijun Shi,Lu Lv,Haiyong Gu,Cheng Qian,Huiwen Pan,Yu Fan,Tao Long,Jingfeng Zhu,Yangyong Sun,Qun Wang,Guowen Ding,Hao Ding,Weifeng Tang,Suocheng Chen,Jun Yao,Lijie Tan,Jun Yin

doi:10.18632/oncotarget.20675

Abstract

BackgroundEsophageal cancer (EC) remains one of the major causes of cancer incidence and mortality worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of EC.MethodsWe conducted a hospital based case-control study to evaluate the genetic susceptibility of SNPs on the development of EC. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. Seven PADI4 SNPs were determined by ligation detection reaction method.ResultsOur findings suggested that the PADI4 rs2240337 GA/AA variants were significantly associated with decreased risk of ESCC. Haplotype PADI4 Ars2477137Crs1886302Grs11203366Grs16825533Grs2240337Ars1635564Ars1635562 and Crs2477137Trs1886302Grs11203366Ars1635564Grs2240337Crs1635564Trs1635562 polymorphism was correlated with decreased susceptibility to ESCC, while Crs2477137Trs1886302Ars11203366Ars1635564Grs2240337Ars1635564Ars1635562 was correlated with increased susceptibility of ESCC. Stratification analyses demonstrated that smoking significantly increased ESCC risk in PADI4 rs11203366 AG/AA, rs1886302 CC/CT, rs1635562 AT, rs1635564 CA and rs2477137 AC genotype. Alcohol drinking increased ESCC risk in PADI4 rs11203366 AG, rs1635562 AT, rs1635564 CA, rs2477137 AC, rs1886302 CT genotype. In younger cohort (<63 years), rs11203366 AA genotype was associated with increased risk of ESCC. PADI4 rs1886302 CC variant was associated with ESCC susceptibility in female cohort.ConclusionsOur study suggested that PADI4 rs2240337 G>A polymorphism may be correlated with individual susceptibility to ESCC. PADI4 rs11203366, rs1886302, rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered susceptibility of ESCC based on sex, age, smoking status and alcohol consumption. However, larger studies among different ethnic populations and further experiments using genetically mutated cells or animals are warranted to verify our conclusion.

Highlights

RESULTSEsophageal cancer is one of the most common cancers worldwide, and carries a high mortality after diagnosis following the onset of symptoms [1]
Our study suggested that peptidylarginine deiminase type 4 (PADI4) rs2240337 G>A polymorphism may be correlated with individual susceptibility to esophageal squamous cell carcinoma (ESCC)
PADI4 rs11203366, rs1886302, rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered www.impactjournals.com/oncotarget susceptibility of ESCC based on sex, age, smoking status and alcohol consumption

Summary

Introduction

RESULTSEsophageal cancer is one of the most common cancers worldwide, and carries a high mortality after diagnosis following the onset of symptoms [1]. ESCC dominates in most parts of the world, especially in high-risk areas such as China, where it accounts for about 90% of the total esophageal cancer cases [2, 3]. Recent study using immunohistochemistry further verified a significant PADI4 expression in various malignancies, comprising esophageal squamous cancer cells [12]. We postulated that PADI4 might play an important role in the carcinogenesis of the esophageal cancer. Esophageal cancer (EC) remains one of the major causes of cancer incidence and mortality worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of EC

Methods

Results

Conclusion