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

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 A(rs2477137)C(rs1886302)G(rs11203366)G(rs16825533)G(rs2240337)A(rs1635564)A(rs1635562) and C(rs2477137)T(rs1886302)G(rs11203366)A(rs1635564)G(rs2240337)C(rs1635564)T(rs1635562) polymorphism was correlated with decreased susceptibility to ESCC, while C(rs2477137)T(rs1886302)A(rs11203366)A(rs1635564)G(rs2240337)A(rs1635564)A(rs1635562) 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.