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The Expression And Significance Of Base Excision Repair Gene APE And XRCC1 In Colorectal Carcinoma

Posted on:2008-06-29Degree:MasterType:Thesis
Country:ChinaCandidate:J P ZhaoFull Text:PDF
GTID:2144360212983941Subject:Pathology and pathophysiology
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Background and Objective In recent years, with the change of living habits in China, the incidence of disease and death rate of colorectal carcinoma appears a rising trend. The rate that the patients could live is almost 100% after operation in the early stage, it decreases gradually with the disease develops. So early treating is a critical factor to cure colorectal carcinoma. The base of treating early is to find and diagnose early. In the early stage, colorectal carcinoma has no obvious symptom which could be found easily, once the patient has the symptom of having blood in stool , the colorectal carcinoma has already gone into the advanced stage and the patient lost the best opportunity of operation. One of the factors to cause this kind of situation is that the mechanism of colorectal carcinoma is not clarified yet. So we have to investigate deeply for the mechanism of colorectal carcinoma so that we could build an effective early warning stage and find colorectal carcinoma easily. It is usually known that the mutation of DNA in the cell could not be restored by physical and chemical factors. The important reason is that the DNA exists and cumulates for a long time. There are many DNA damage restoration system in the cell when the organism is in the long course of evolution in order to keep stability. There are five ways for DNA damage which are known currently. In the five ways, the loss of function of mismatch repair has a close relation with the colorectal carcinoma, but is there any relation between the repair way and the colorectal carcinoma out of mismatch repair? In this article we discussed the relation between the base excision repair and the colorectal carcinoma. Base excision repair is to excise and restore bases so thatgenetic protein could restore normal DNA double-helix structure, thus it prevents genetic mutation and keeps the genetic stability. APE is one of the important members in BER, the main function is to restore apurinic/apyrimidinic site by the damage of alkylator and oxidation and adjust the genetic expression of cells. XRCC1 also participates in BER, it restores DNA damage caused by all kinds of damage by single-strand restoration. The occurrence of colorectal carcinoma is a very complicated process, colorectal mucosa cell is an unstable cell and easily be damaged by all sorts of noxious substance, any kind could cause the genetic mutation if they are not be repaired in time. Nowadays there are few literature about the relation between the base excision repair and the colorectal carcinoma. In this study we detected BER gene APE,XRCC1's expression in colorectal carcinoma, adjacent mucosa and normal mucosa and discussed the relationship between BER and the colorectal carcinoma.Material and method Colorectal carcinoma specimens were obtained surgically from 185 patients, including adjacent mucosa from 32 patients, normal mucosa from 36 patients. Immunohistochemistry was used to detect the expression of APE,XRCC1 protein in each specimen, and analyzed the relation between the expression and sex, age, tumor location, differentiation degree, chorion invasion and lymphatic metastasis. SPSS 13.0 statistic software was used to analyze the data.Results APE protein is expressed in cell nucleus and also cell plasm. In colorectal carcinoma , adjacent mucosa group, the expression of APE are 78.9%(146/185),81.2%(26/32),which are much higher than the one in the normal group 61.1%(22/36)(P<0.05), but there is no significant difference between the former two(P>0.05). There is no obvious correlation between APE and sex, age, tumor location, differentiation degree, chorion invasion and lymphatic metastasis(P>0.05).XRCC1 protein is mainly expressed in cell nucleus. In colorectal carcinoma , adjacent mucosa group, the expression of XRCC1 are 94.6%(175/185),87.5%(27/32),which are much higher than the one in the normal group 27.7%(10/36)(P<0.05), but there is no significant difference between the former two(P>0.05). There is no obvious correlation between XRCC1 and sex, age, tumor location, differentiation degree, chorioninvasion and lymphatic metastasis(P>0.05).The expression of APE in positive XRCC1 cases 95.8%(136/142) is much higher than the one in negative XRCC1 cases 86%(37/43). There is obvious positive correlation between two of them(r=0.354, P<0.05). The positive rates that APE and XRCC1 expressed simultaneously in colorectal carcinoma, adjacent mucosa are 75.8%(140/185),65.6%(21/32), they are much higher than the one in normal mucosa 16.7% ( 6/36 )(P<0.05),but there is no significant difference between them(P>0.05).Conclusions:1. The expression rates of APE and XRCC1 are increased in colorectal carcinoma.2. The expression rates of APE and XRCC1 are increased in colorectal adjacent mucosa.3. The occurrence of colorectal carcinoma maybe has a close relation with the damage of the site and noxious substance like alkylator in DNA replication.4. To detect different kinds of expression of DNA repair gene in the same time in colorectal mucosa is helpful to early diagnosis for colorectal carcinoma.
Keywords/Search Tags:colorectal carcinoma, base excision repair, APE, XRCC1
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