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Research On The Association Of Angiotensin-converting Enzyme Gene Polymorphism With Colorectal Carcinogenesis And Lymph Node Metastasis

Posted on:2019-10-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:X ZhengFull Text:PDF
GTID:1364330545455091Subject:Surgery
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Colorectal cancer(CRC)is one of the most common malignant tumors of the digestive tract.China is a low-risk area in the world,but with the development of economy,the improvement of living standards,the change of dietary structure and the influence of genetic factors,the incidence of colorectal cancer in China is increasing year by year.Early diagnosis and early treatment of colorectal cancer are closely related to the five-year survival rate.Statistics indicate that colon cancer has early detection and early treatment of cancer,and its five-year survival rate is 90%.However,many countries still lack effective means for early screening,and less than40% of patients are diagnosed early in the tumor.The 5-year survival rate of colorectal cancer in Asian countries is close to 60%.Clinically diagnosed as early colorectal cancer is rare,the majority of patients have reached the advanced stage of treatment,and about half of the patients are diagnosed as colorectal cancer with local or distant metastatic symptoms.At present,the treatment of colorectal cancer mainly includes comprehensive treatment including surgery,chemotherapy,radiotherapy,and targeted therapy,and surgery is the first choice for the treatment of tumors.Although some advances have been made in radiotherapy and chemotherapy and targeted therapies,its overall The 5-year survival rate is still not satisfactory.The main reason is that due to tumor metastasis,including lymph node metastasis,direct invasion of adjacent organs and hematogenous metastasis,leading to tumor recurrence,is one of the main reasons for treatment failure.Therefore,the focus of the current research is mainly on the pathogenesis of colorectal cancer and the study of tumor metastasis mechanism.It has certain guiding significance for the prevention of colorectal cancer and improving the five-year survival rate.The exact mechanism of the occurrence and development of colorectal cancer has not been specifically clarified.At this stage,basic research on tumors is divided into four aspects: cellular level,DNA level,RNA level,and protein level.There is relatively little research on the relationship between genetic polymorphisms and colorectal cancer at the DNA level.Studies have shown that genetic polymorphisms can cause alterations in DNA spatial structure,which in turn lead to functional changes that ultimately affect DNA transcriptional functions,resulting in changes in the corresponding translated protein products,and involvement in the development of diseases.At present,it has become a hot spot in gene research.The relationship between certain polymorphisms and diseases has been confirmed.Angiotensin-converting enzyme(ACE)is mainly expressed in vascular endothelial cells of the lung and kidney and is associated with the pathogenesis of heart,brain and kidney.Angiotensin-converting enzyme is a key enzyme of the renin-angiotensin system(RAS)and plays an important role in maintaining the balance of water and sodium electrolytes in the circulatory system.The angiotensin-converting enzyme(ACE)gene is located in the 3rd region of the long arm of human chromosome 17,and there is a 287 base Alu sequence insertion(I)and deletion(D)polymorphism in the 16 th intron of the ACE gene.Sex,and then formed three genotypes: II,ID and DD.Studies have confirmed that this polymorphism is associated with serum ACE levels,and the deletion of allele(D)ACE levels is significantly increased.A large number of studies have found that angiotensin-converting enzyme is expressed on many kinds of tumors,and can affect the biological behaviors such as tumor proliferation,tumor cell migration,angiogenesis and metastasis.At the same time,studies have found that angiotensin-converting enzyme inhibitors(ACEI)can significantly reduce the risk of cancer and related mortality.However,there are also reports that the polymorphism of the angiotensin converting enzyme gene has nothing to do with tumorigenesis but is related to race.Our role in ACE polymorphisms in the development of colorectal cancer remains unclear.To further clarify the possible relationship between ACE gene polymorphism and colorectal cancer,146 patients with colorectal cancer within Tai'an City were studied in this study.Objective to investigate the potential relationship between ACE gene I/D polymorphisms and the occurrence of colorectal cancer,and to further analyze the relationship between ACE gene polymorphisms and tumor lymph node metastasis,and provide scientific basis for tumor prevention and treatment.Part I The relationship between angiotensin-converting enzyme gene polymorphism and the occurrence of colorectal cancerObjective:This study aimed to investigate the distribution of angiotensin-converting enzyme gene polymorphism(ACE)in normal and colorectal cancer patients.And the correlation between ACE gene polymorphisms and the occurrence of colorectal cancer.MMethods:We detected ACE gene polymorphisms in 146 Chinese Han patients with colorectal cancer and 106 healthy controls.Then,through case-control analysis,the relationship between ACE gene polymorphisms and susceptibility to colorectal cancer was studied,and relevant clinical data were collected to analyze the relationship between general clinical data and the occurrence of colorectal cancer.RResults:1.There was no significant difference in clinical data between the colorectal cancer group and the healthy control group.2.The frequency distribution of ACE I / D polymorphism in patients with colorectal cancer(CRC)was different from that in healthy controls.The frequency of occurrence of ?,ID and DD phenotypes in colorectal cancer patients was: 26.03%,50.68%and 23.29%respectively,while the frequency of occurrence of ?,ID and DD phenotypes in the healthy control group was: 38.68%,45.28% and 16.04%3.The ACE DD genotype was observed more frequently in CRC patients than in healthy controls(23.29% vs.16.04%),indicating that the DD genotype is a risk factor for the development of CRC(P= 0.038,OR = 2.158,95% Cl = 1.039-4.480).4.The D allele frequency showed a significant increase in the CRC patient group,and the D allele significantly increased CRC susceptibility(P = 0.026,OR = 1.501,95% CI = 1.048-2.150).Conclusion:The frequency distribution of ACE I / D polymorphisms in patients with colorectal cancer(CRC)was different from that in healthy controls;ACE DD genotype was a risk factor for CRC development.The D allele is significantly associated with the risk of CRC.Part ? Correlation of Angiotensin Converting Enzyme Gene Polymorphism with Lymph Node Metastasis in Colorectal CancerObjective:The purpose of this study was to investigate the distribution of angiotensin converting enzyme gene polymorphism(ACE)in lymph node metastasis and non-lymph node metastasis of colorectal cancer patients.And the association of ACE gene polymorphism with lymph node metastasis in colorectal cancer.Methods:We divided 146 colorectal cancers into lymph node metastasis group and non-lymph node metastasis group according to lymph node metastasis.Individual ACE gene polymorphisms were detected.Then through case-control analysis,we studied the relationship between ACE gene polymorphisms and lymph node metastasis of colorectal cancer,and general clinical data were collected to analyze the relationship between ACE gene polymorphism and lymph node metastasis of colorectal cancer.Results:1.The general clinical data of lymph node metastasis group and non-lymph node metastasis group had no significant difference.2.The frequency distribution of ACE I / D polymorphism in patients with lymph node metastasis of colorectal cancer(CRC)is different from those without lymph node metastasis,and the phenotypes of ?,ID and DD in patients with lymph node metastasis and colorectal cancer are different.The frequencies were: 18.18%,50.00%,and 31.82%,respectively.The frequencies of the ?,ID,and DD phenotypes in the non-lymphatic metastasis group were: 32.50%,47.50%,and 20.00%.3.ACE DD genotypes were more frequently observed in patients with CRC lymph node metastases than in those without lymph node metastases(31.82%vs.20.00%).The DD genotype was significantly associated with the risk of lymph node metastasis in CRC patients(P = 0.028,OR = 2.844,95 % CI = 1.107-7.038).4.The D allele frequency showed a significant increase in the CRC lymph node metastasis group,and the D allele significantly increased the susceptibility to CRC lymph node metastasis(P = 0.026,OR = 1.692,95% CI = 1.063-2.693).Conclusion:The frequency distribution of ACE I / D polymorphism in patients with colorectal cancer(CRC)lymph node metastasis was different from that in non-lymph node metastasis;ACE DD genotype was a risk factor for CRC lymph node metastasis.The D allele was significantly associated with the risk of CRC lymph node metastasis.
Keywords/Search Tags:colorectal cancer, angiotensin converting enzyme I/D gene polymorphism, lymph node metastasis
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