MUC5AC Upstream Complex Repetitive Region Length Polymorphisms Are Associated with Susceptibility and Clinical Stage of Gastric Cancer

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.鉴于胃癌（GC）患者中反复检测到黏蛋白5AC（MUC5AC）异常表达，故认为MUC5AC参与胃癌发生过程。本研究针对230例胃癌患者与328例非癌症对照人群，对MUC5AC启动子邻近的复杂重复区域的长度多态性进行了分析。结果显示，1.4kb与1.8kb等位基因在胃癌组中的分布频率显著高于对照组；与之相反，2.3kb与2.8kb等位基因在患者群体中的分布频率则显著低于对照组。随后，根据等位基因与胃癌易感性的关联程度，将其分为易感型（S；1.4kb与1.8kb）、保护型（P；2.3kb与2.8kb）以及无效型（N；其余所有等位基因）三类。携带SS基因型的个体发生胃癌的风险升高2.7倍，而PN基因型则与胃癌发病风险的显著降低相关。此外，相较于未携带1.4kb等位基因的患者，携带1份或2份1.4kb等位基因的杂合或纯合个体发病年龄更早，转移分期更晚（经Bonferroni校正后的P值分别为1.35×10⁻⁴与6.60×10⁻⁴）；而携带2份1.8kb等位基因的纯合患者则与更低分期的胃癌TNM分期相关。本研究结果表明，MUC5AC上游重复区域的特定遗传变异与胃癌的易感性及疾病进展相关。