MMP-2和TIMP-2基因启动子区多态性与卵巢上皮性癌关系的研究

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为探讨MMP-2和TIMP-2基因启动子区单核苷酸多态性(SNPs)与卵巢上皮性癌发病风险的关系,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测了246例卵巢上皮性癌患者和324例对照妇女的MMP-2C-1306T、C-735T和TIMP-2G-418C3个SNPs的基因型。结果显示,MMP-2C-1306TSNP的等位基因及基因型频率分布在卵巢癌与对照组间无显著差异(P=0.55和P=0.42);但卵巢癌组MMP-2C-735TSNP的C等位基因和C/C基因型频率(80.7%和66.7%)明显高于对照组(75.5%和55.9%),与T/T+C/T基因型比较,携带C/C基因型可以显著增加卵巢癌的发病风险(OR=1.58,95%CI=1.12~2.23),进一步分层分析显示,C/C基因型主要与宫内膜样癌和年龄≥50岁妇女的发病风险显著相关,OR值分别为1.69(95%CI=1.03~2.79)和1.71(95%CI=1.14~2.57);对MMP-2C-1306T、C-735T2个SNPs的单体型分析显示,4种单体型频率(T-1306-T-735、T-1306-C-735、C-1306-T-735和C-1306-C-735)在两组间分布无显著差异(P=0.24);虽然TIMP-2G-418CSNP的等位基因及基因型频率在卵巢癌组与对照组间分布无显著性差异(P=0.33和P=0.47),但以病理类型分层分析显示,携带TIMP-2G-418G/G基因型有增加宫内膜样癌发病风险的趋势(OR=1.62,95%CI=0.94~2.78)。以上结果提示,MMP-2基因启动子区C-735TSNP的C/C基因型可能是卵巢上皮性癌发病的潜在危险因素,而C-1306TSNP可能与卵巢上皮性癌的发病风险无关;TIMP-2G-418CSNP可能与不同病理类型的卵巢上皮性癌发病风险有关。 To investigate the relationship between SNPs in the promoter region of MMP-2 and TIMP-2 gene and the risk of epithelial ovarian cancer, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) ) Method was used to detect the genotypes of MMP-2C-1306T, C-735T and TIMP-2G-418C3 SNPs in 246 patients with epithelial ovarian cancer and 324 control women. The results showed that there was no significant difference (P = 0.55 and P = 0.42) between the frequency of allele and genotype of MMP-2C-1306TSNP in ovarian cancer and control group. However, the C allele of MMP-2C-735TSNP in ovarian cancer The frequency of genotype and C / C genotype (80.7% and 66.7%) was significantly higher than that of the control group (75.5% and 55.9%). Compared with T / T + C / T genotype, C / C genotype could significantly increase ovarian (OR = 1.58, 95% CI = 1.12-2.23). Further stratified analysis showed that the C / C genotype was mainly associated with the risk of endometrial carcinoma and women over 50 years of age, and the OR value Were 1.69 (95% CI = 1.03 ~ 2.79) and 1.71 (95% CI = 1.14 ~ 2.57) respectively. The haplotype analysis of the two SNPs of MMP-2C-1306T and C-735T showed that the frequencies of four haplotypes T-1306-T-735, T-1306-C-735, C-1306- T-735 and C-1306- C-735) did not differ significantly between the two groups (P = 0.24) -418CSNP allele and genotype frequency in the ovarian cancer group and control group distribution was no significant difference (P = 0.33 and P = 0.47), but by pathological type stratification analysis showed that carrying TIMP-2G-418G / G Genotypes increased the risk of endometrial carcinoma (OR = 1.62, 95% CI = 0.94-2.78). The above results suggest that the C / C genotype of C-735TSNP in the promoter region of MMP-2 gene may be a potential risk factor for the pathogenesis of epithelial ovarian cancer, while C-1306TSNP may not be associated with the risk of epithelial ovarian cancer. TIMP-2G -418CSNP may be related to the different pathological types of epithelial ovarian cancer risk.
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