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The Screening for Pancreatic Cancer in Asymptomatic Community Populations Using the High Risk Scoring Model and the Preliminary Study of SNP Applications in High Risk Populition

Author: ShiYiHai
Tutor: QianJiaMing;LiJingNan;YangHong
School: Peking Union Medical College , China
Course: Department of Gastroenterology,
Keywords: Pancreatic Cancer Risk model Single nucleotide polymorphisms Community groups Diabetes
CLC: R735.9
Type: PhD thesis
Year: 2009
Downloads: 235
Quote: 0
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Abstract


Pancreatic cancer is a clinical manifestation of occult, the rapid development and poor prognosis of gastrointestinal cancer, early diagnosis is to improve the survival rate of pancreatic cancer, the most effective way. However, the vast majority of the crowd because of symptoms of treatment in patients with advanced, has lost the best time for treatment. Establish asymptomatic high-risk groups and regular follow-up is to raise the key rate of early diagnosis of pancreatic cancer. Those with a family history of pancreatic cancer abroad and / or suffering from certain genetic syndromes (such as hereditary pancreatitis, HNPCC, PJ syndrome) is defined as high risk individuals for screening, access to the encouraging results, the follow-up of asymptomatic high risk screening strategies for people to accept. However, sporadic pancreatic cancer reported in the literature China accounted for 90% to 95% or more; how to identify sporadic pancreatic cancer in asymptomatic high-risk groups at home and abroad have been reported. Wang Li and other studies suggest carrying MTHFR -677 CT and TT genotype had pancreatic cancer risk genotype CC 2.17 and 3.53 times, suggesting that certain genes carry single nucleotide polymorphisms (SNPs) of the population may be with a high risk of cancer genetic susceptibility. Comprehensive assessment of environmental and genetic factors determine the screening of asymptomatic high-risk groups is an important way for early detection of pancreatic cancer. Domestic and international research suggests that the incidence of pancreatic cancer patients with diabetes increased from 1 to 8 times the range, new-onset diabetes in patients with pancreatic cancer, the annual incidence of up to 0.31%, significantly higher than the general population incidence. Diabetes is a high risk of pancreatic cancer, pancreatic cancer still remains an early manifestation of research in China, was established diabetes cohort studies / clear the issue important foundation. Thus, by looking for SNPs studied genetic risk of pancreatic cancer, and with the combination of high-risk scoring models, hoping to get sporadic pancreatic cancer in asymptomatic high-risk groups, for whom follow-up can be really early diagnosis of pancreatic cancer. In this study, Beijing Union Medical College Hospital, the first to establish a high-risk rating model for the asymptomatic population, first verify its asymptomatic high-risk groups in the community, the application value, and explore related gene polymorphisms and risk scoring model combining asymptomatic population in the community feasibility of the application. Therefore, the goal of early diagnosis of pancreatic cancer, pancreatic cancer in asymptomatic high-risk groups how to establish the center, this study from pancreatic cancer susceptibility SNPs, hospital-acquired pancreatic cancer \coarse sieve and queues build crowd started to study aims to: 1. investigate the expression of immune-related genes CTLA-4 and CD86 SNPs with pancreatic cancer genetic susceptibility; 2. evaluation of risk scoring model community in determining the application of asymptomatic high-risk groups value; and explore related gene polymorphisms and risk scoring model combining feasibility; 3. establish the relationship between diabetes and pancreatic cancer, a prospective cohort study. a cellular immune-related gene single nucleotide polymorphisms and the risk of pancreatic cancer Association Study Methods: PCR-RFLP and PCR-SSP method, 138 cases of pancreatic cancer patients and 278 normal controls were immune related genes CTLA-4 rs231775, rs5742909 and CD86 rs1129055, rs9831894 genotyping results: 1. CTLA-4 gene rs231775 polymorphism associated with increased risk of pancreatic cancer, carrying rs231775AG-AA genotype pancreatic cancer risk GG genotype was 1.93 (95% CI :1.24-3 .01, P = 0.0032) times. 2 . CD86 gene rs9831894 polymorphism associated with increased risk of pancreatic cancer, carrying rs9831894 CC genotype pancreatic cancer risk is AA-AC genotype 2.27 (95% CI :1.03-4 .98, P = 0.042) times. 3 Haplotype analysis showed that the haplotype analysis showed that carrying rs1129055 G-rs9831894 C haplotype risk of pancreatic cancer who are rs1129055A-rs9831894A haplotype's 1.59 (95% CI :1.01-2 .50, P = 0.048) times . Summary: This study demonstrated CTLA-4 and CD86 single nucleotide polymorphisms and the risk of pancreatic cancer there is a correlation between, is likely to determine individual genetic susceptibility to pancreatic important factor two, asymptomatic pancreatic cancer risk application scoring model community groups and Preliminary Application of SNPs Methods: A hospital-based to establish a \asymptomatic sub-populations at high risk of pancreatic cancer is defined as the follow-up, and to verify / evaluate risk scoring model community asymptomatic high-risk populations in determining the application value. using PCR-RFLP method for high-risk populations CA19-9 ≥ 37U/ml 25 patients were CTLA-4 rs231775 genotyping, and with pancreatic cancer group and normal control group were compared. Results: 1. were screened 29,550 people; identify people at high risk of 1173, accounting for 3.9% of those surveyed, the average score of 65.3 ± 17.8 minutes; non-high-risk groups an average score of 8.7 ± 8.7 points, there were significant differences between the two groups (P <0.0001). 2.2 year follow-up were found in three cases of pancreatic cancer patients, including two cases of advanced pancreatic cancer, pancreatic cancer, one case of early , and also found in other gastrointestinal tumors four cases. 3.CTLA-4 gene rs231775 genotype in CA19-9-positive group, pancreatic cancer and control groups were not significantly different. Summary: The screening program can be screened population concentration was 3.9% at high risk, high risk initially validated scoring model community application value. Third, the relationship between diabetes and pancreatic cancer, a prospective cohort study of initial establishment Methods: Since 2009, Daqing Oilfield General Hospital Group, an 86 community health service stations registration and management of chronic diseases in diabetic patients as research subjects, to keep the new cohort included patients with new-onset diabetes through community health service stations chronic disease management registration, Daqing City, the CDC tumors and death registration and regular follow-up for outcome variables. Results: A total of Daqing Oilfield General Hospital Group belongs 86 community health service stations registration and management of patients with diabetes were 2217 cases, the median age at diagnosis of 52.7 years, mean diabetes on average 85.8 ± 55.20 months. new-onset diabetes (≤ 24 month) 273 cases, accounting for 12.3%. were registered first-degree relatives of patients with diabetes (including the patient's parents and children) 6602 people, with a median age of 55.9 years old. Summary: In Daqing City, the establishment of a reliable and informative, scientific design, easy-to long-term Prospective Diabetes follow-up cohort. CONCLUSION: 1.CTLA-4 and CD86 single nucleotide polymorphisms and the risk of pancreatic cancer there is a correlation between, is likely to determine individual genetic susceptibility to pancreatic important factor; 2. preliminary validation of the scoring model of pancreatic cancer at high risk of asymptomatic community value of the application; 3 in Daqing City, the establishment of a reliable and informative, scientific design, easy-to long-term follow-up of prospective cohort diabetes.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Pancreatic tumors
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