Research Papers:

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

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

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Oncotarget. 2017; 8:93655-93671. https://doi.org/10.18632/oncotarget.20675

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Liming Wang1,*, Haiyong Gu2,*, Tao Long2,*, Huiwen Pan2, Lu Lv2, Yijun Shi2, Jingfeng Zhu2, Yangyong Sun2, Weifeng Tang2, Guowen Ding2, Suocheng Chen2, Yu Fan1, Hao Ding3, Cheng Qian4, Qun Wang4, Jun Yao5, Lijie Tan4 and Jun Yin2,4

1Cancer institute, Department of Chemotherapy, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

3Department of Respirology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

4Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China

5Department of Gastroenterology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

*Liming Wang, Haiyong Gu and Tao Long contributed equally to this work

Correspondence to:

Jun Yin, email: [email protected]

Lijie Tan, email: [email protected]

Jun Yao, email: [email protected]

Keywords: PADI4, polymorphisms, esophageal squamous cell carcinoma, molecular epidemiology

Received: March 13, 2017     Accepted: July 18, 2017     Published: September 06, 2017


Background: 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: We 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.

Results: Our 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.

Conclusions: Our 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.

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