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Analysis To Influence Of MMPs And MTHFR Polymorphisms On Susceptibility Of Cervical Cancer

Posted on:2017-10-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:B B XieFull Text:PDF
GTID:1314330512452722Subject:Obstetrics and gynecology
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BackgroundThe incidence of cervical cancer is rising in our country, with an increase in young women especially. It is well known that cervical cancer is caused by human papillomavirus (HPV) infection. However,only a small percentage of infected women would finally develop into cervical cancer. Cervical cancer is caused by both the genetic and environmental factors, so the genetic factors including genetic polymorphisms have become the important directions of reseach on cervical cancer. Matrix metalloproteinases (MMPs) are proteolytic enzymes depend on the metal zinc or ions, which can effectively degradate the extracellular matrix (ECM), play an important role in growth, angiogenesis and migration of cancer. However the relationship between cervical cancer and the gene polymorphisms has not yet been reported widely. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme which play an important role in the metabolism process of folate, the enzyme activity can affect the metabolism of folic acid, and then participate in a variety of diseases including tumor development. Studies have found that lack of folic acid may increase the risk of cervical cancer, It is reported that MTHFR gene polymorphism is closely related to cervical cancer, but the conclusion is inconsistent. This study aims to explore the association of MMPs and MTHFR gene polymorphism with susceptibility and clinical characters of cervical cancer.ObjectiveExplore the association of MMP2-1306 C/T?MMP3-11715A/6A?MMP7-181A/G? MMP9-1562C/T?MTHFR 677 C/T and MTHFR 1298 A/C with the susceptibility and clinical outcomes of cervical cancer, for it's prevention and therapy.MethodsFrom January 2012-January 2016,230 cervical cancer cases and 230 controls in our hospital are enrolled in our case control study. All the researchers are taken venous blood 3 ml in the morning on an empty stomach,-40 ? refrigerator saved, for blood genomic DNA extraction. Polymerase chain reaction (PCR) method for gene amplification, RFLP analysis of genotype polymorphism of MMP2-1306 C/T? MMP3-11715A/6A?MMP7-181A/G?MMP9-1562C/T?MTHFR 677C/T and MTHFR1298A/C.Cervical cancer (stage ?-?) pathological tissues were collected and placed in liquid nitrogen tank immediately,-80 stored, for extracting DNA. PCR-RFLP was used to detect the expression of gene polymorphisms. Benign uterine cervix were used as control. Chi-square test and Logistic regression method by spss 19.0 Hardy-weinberg balance test of genotype frequency distribution on case group and control; P<0.05 was as significant difference in the standard.ResultsPart 1 MMPs or MTHFR gene polymorphism and cervical cancer1?The genotype frequency distribution of MMP2-1306C/?MMP3-11715A/6A? MMP7-181A/G?MMP9-1562C/T.MTHFR 677C/T and MTHFR1298A/C accords with the Hardy-Weinberg equilibrium, and the object of study was representative.2?MMP2-1306 C/T?MMP7-181A/G and MTHFR 677C/T polymorphisms were significantly associated with cervical cancer.(p<0.05)?3?MMP3-11715A/6A?MMP9-1562C/T and MTHFR1298A/C polymorphisms were not significantly associated with cervical cancer.(p>0.05)?Part 2 MMPs and MTHFR polymorphisms and clinical pathological characteristics of cervical cancer1?MMP2-1306 C/T?MMP7-181A/G and MTHFR 677C/Tpolymorphisms were significantly associated with tumor stages of cervical cancer.(p<0.05)?2?MMP2-1306 C/T?MMP7-181 A/G and MTHFR 677C/T polymorphisms were not significantly associated with lymphnodes metastasis of cervical cancer.(p>0.05)?3?MMP2-1306 C/T?MMP7-181A/G and MTHFR 677C/Tpolymorphisms were not significantly associated with tumor stage and histological type of cervical cancer. (p>0.05)?4?MTHFR gene 677 c/T polymorphism distribution has significant correlation with and MMP2 gene polymorphism, and have no significant correlation with MMP7.ConclusionMTHFR 677C/T?MMP2-1306 C/T and MMP7-181A/G genetic polymorphism was significantly associated with the occurrence and staging of cervical cancer, Specific clinical intervention programs can be conducted on patients according to different genotypes.
Keywords/Search Tags:MMP, MTHFR, Genetic polymorphism, Cervical cancer
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