When the PADI4 rs2240337 G>A SNP GG homozygote genotype (AA) was used as the reference group, both the GA heterozygote genotype (AB) and the AA mutated homozygote genotype (BB) were associated with a significantly decreased risk of ESCC (AB vs. AA: adjusted OR = 0.52, 95% CI = 0.39-0.71, p<0.0001; BB vs. AA: adjusted OR = 0.30, 95% CI = 0.13-0.68, p = 0.004). The gene discussed is PADI4; the disease is esophageal squamous cell carcinoma.