MUC5AC was deemed to be involved in gastric carcinogenesis since aberrant MUC5AC expression has been repeatedly detected in patients with gastric cancer (GC). In this study, length polymorphisms in a complicated repetitive region adjacent to MUC5AC promoter were assessed in 230 patients with GC and 328 cancer-free controls. Alleles of 1.4 and 1.8 kb were significantly more prevalent in GC group than in controls. In contrast, 2.3 and 2.8 kb alleles occurred at significantly lower frequencies in patients than in controls. Alleles were then classified into susceptible (S; 1.4 and 1.8 kb), protective (P; 2.3 and 2.8 kb) and null (N; all other alleles) categories with respect to their linkage with the susceptibility to GC. Individuals with genotype SS had a 2.7-fold increased risk of GC occurrence, but PN genotype was associated with a significantly reduced risk of this cancer. Moreover, homozygous or heterozygous individuals with one or two copies of 1.4 kb allele showed an earlier age of onset and more advanced metastasis stage compared with patients without this allele (Bonferroni corrected p = 1.35×10(-4) and 6.60×10(-4) accordingly), whereas homozygous patients with two copies of 1.8 kb allele were linked to less advanced GC TNM stage. Our results suggest that certain genetic variations in MUC5AC upstream repetitive region are associated with the susceptibility and progression of GC.