MMP-2基因启动子区单核苷酸多态性与高发区食管癌易感性的关系

Association of single nucleotide polymorphisms in the promoter region of MMP-2 gene with susceptibility to esophageal squamous cell carcinoma in high prevalence area

目的:采用病例-对照研究,探讨基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)启动子区C-1306T和C-735T单核苷酸多态性(single nucleotide polymorphisms,SNP)与河北省食管癌高发区-磁县食管鳞状细胞癌(esophageal squa-mous cell carcinoma,ESCC)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术检测335例ESCC患者和624名健康对照的MMP-2C-1306T和C-735TSNP的基因型频率分布。结果:MMP-2基因启动子区C-1306T多态的基因型及等位基因频率分布在ESCC患者组与对照组之间差异有统计学意义(Pgenotype=0.01和Pallele=0.02),与C/T+T/T基因型相比,C/C基因型显著增加ESCC的发病风险(OR=1.57,95%CI=1.10～2.23);以家族史和吸烟状况分层分析显示,C/C基因型可显著增加家族史阳性和吸烟个体的发病风险(OR=2.06和1.96,95%CI=1.19～3.55和1.09～3.53)。C-735T多态的基因型及等位基因频率分布在ESCC患者组与对照组之间差异无统计学意义(P>0.05)。结论:MMP-2基因启动子区C-1306T多态的C/C基因型可能是河北省磁县ESCC发病的危险因素,尤其可以增加家族史阳性及吸烟人群的发病风险;而C-735TSNP可能与食管癌发病风险无关。

Objective：To investigate the association of the C-1306T and C -735T functional single nucleotide polymorphisms （SNPs） in matrix metalloproteinase-2 （MMP-2） with the susceptibility to esophageal squamous cell carcinoma （ESCC） in a high prevalence area, Ci county in Hebei Province by using case-control study. Methods：The frequencies of C - 1306T and C -735T SNP were analyzed by polymerase chain reation-restriction fragment length polymorphism （PCR-RFLP） method in 335 ESCC patients and 624 healthy indMduals without overt cancer in a population of high incidence region in Hebei Province, China. Results：The allele frequencies and genotype distributions of C - 1306T polymorphism in the promoter region of the MMP-2 were significantly different between ESCC group and control group （ P = 0.02 and 0. 01 , respectively）. Compared with the C/T or T/T genotypes, the C/C genotype significantly increased the risk of developing ESCC. The OR was 1.57 （95% CI = 1.10-2.23 ）. When stratified for smoking status and family history, of UGIC, the C - 1306C genotype significantly increased the risk of developing ESCC in those individuals in smoking status （the adjusted OR = 1.96 and 95% CI： 1.09-3.53 ） or with positive family history of upper gastrointestinal complications （ UGIC, the adjusted OR = 2.06 and 95% CI： 1.19-3.55 ）. The genotype distribution and allele frequency of C - 735T polymorphism in the promoter region of the MMP-2 gene were not significantly different between ESCC group and control group （P 〉 0.05）. Conclusion：This study indicated that C/C genotype of C - 1306T SNP in the promoter region of MMP-2 could be the independent risk factor for developing ESCC, especially for those in the smoking status and with family history of UGIC. But the SNP of C -735T may be not related with the risk of developing ESCC.