Summary of doctoral thesis in medicine: Study on single nucleotide polymorphism of MUC1 and PSCA gene in gastric cancer patients

Single-nucleotide polymorphisms (SNP) are common genetic changes in the human genome. In recent time, many scientists have shown their interests in studies on SNPs’ roles in the pathological risk especially in cancer and metabolic diseases.
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Summary of doctoral thesis in medicine: Study on single nucleotide polymorphism of MUC1 and PSCA gene in gastric cancer patients MINISTER OF EDUCATION MINISTER OF HEALTH HA NOI MEDICAL UNIVERSITY NGUYEN THI NGOC LAN STUDY ON SINGLE NUCLEOTID POLYMORPHISMS OF MUC1 GENE AND PSCA GENE IN GASTRIC CANCER PATIENTS Specialty : Biochemistry Code : 62720112 SUMMARY OF DOCTORAL THESIS IN MEDICINE HA NOI - 2020 The work was completed at: HA NOI MEDICAL UNIVERSITY Supervisor: Prof. Ta Thanh Van Assoc Prof. Dang Thi Ngoc Dung Review 1: Assoc Prof.PhD. Bach Khanh Hoa Review 2: Assoc Prof.PhD. Bach Vong Hai Review 3: Prof.PhD. Tran Van Thuan The thesis was defended before the Council at the university level Meeting at: Ha Noi Medical University On: The thesis can be found in the library: - National Library - The Library of Ha Noi Medical University THE RESEARCH RELATED TO THE THESIS 1. Nguyen Thi Ngoc Lan, Dang Thi Ngoc Dung, (2018), Research on pepsinogen concentration and some related factors in patients with stomach cancer, Vietnam Journal of Medicine, Specialized issue Topic (469), 87 - 94. 2. Tran Van Chuc, Nguyen Thi Ngoc Lan, Dang Thi Ngoc Dung, Ta Thanh Van (2018), Single polymorphism rs2294008 PSCA gene and risk of gastric cancer, Journal of Medical Research, 6 (115), 25-32. 3. Nguyen Thi Ngoc Lan, Nguyen Van Tan, Ta Thanh Van, Dang Thi Ngoc Dung (2019), Identification the polymorphism rs4072037 of MUC1 gene in patients with gastric cancer, Journal of Medicine Research, 2 (118 E4), 8-15. 1 INTRODUCTION Gastric cancer (GC), which is statistically proven to be the fifth most common cancer and the third leading cause of cancer death, is a malignant disease. The pathogenesis of GC is a complex process involving factors such as Helicobacter pylori (H.pylori) infection, diets, lifestyles and genetics. With regard to genetic changes, Single Nucleotide Polymorphism (SNP) is one of the common types of genetic variants in the human genome. Nowadays, a plenty of researchers in some countries with high prevalence of GC patients such as Japan, South Korea and China tend to carry out investigations on SNPs of MUC1 and PSCA, the promising findings of which indicated that these SNPs are potential markers for screening GC risks. MUC1 encodes the mucin-1 protein, which prevents exogenous factors from causing damages to cells under normal conditions. In addition, PSCA has been shown to be linked to many cancers including GC. Although Vietnam is a country with a high rate of patients with GC, the number of studies on genetic variants such as SNPs on GC patients, especially the combination of these SNPs with the risk factors of GC is still small and with lots of limitations. For the above reasons, the research Study on Single Nucleotide Polymorphism of MUC1 and PSCA gene in gastric cancer patients was conducted with the following objectives: 1) Identify single nucleotide polymorphisms of MUC1 and PSCA genes among patients with Gastric cancer. 2) Assess the correlation between MUC1 and PSCA polymorphisms and z risk factors of gastric cancer. 1.1. Urgency Single-nucleotide polymorphisms (SNP) are common genetic changes in the human genome. In recent time, many scientists have shown their interests in studies on SNPs’ roles in the pathological risk especially in cancer and metabolic diseases. ... Many SNPs including the ones of MUC1 and PSCA were reported to have relation with GC. 2 The studies on combination of these SNPs with risk factors including H.pylori infection, drinking history, or smoking history, etc. was launched. The risk of getting diseases in general and GC in particular is a combination of risk factors and genetic factors. Research on SNPs of MUC1 and PSCA especially on their combination with risk factors in GC has not been studied in Vietnam. These are the reasons pushing the research to be conducted. New contributions of the thesis - It is identified that SNPs including AA genotype of rs4072037 and GG genotype of rs2070803, both belonging to MUC1 gene, increase the risk of GC development. - No matter what risk factor is in combination with MUC1’s sensitive genotypes does the risk of GC development increase. Especially when these genotypes combine with the family history of GC, patients have six times higher risks of suffering from it. When these SNP genotypes combine with each other, only the combination of one of the two above mentioned sensitive genotypes increases the risk of GC. A prognosis model of GC based on age, history of individual gastrointestinal disease, family history of GC, drinking history and rs4072037 (MUC1) was developed. Model test results obtained AUC = 70%, accuracy = 0.63, Brier index = 0.231. Layout of the thesis - The 123-page- thesis includes the following parts: 2-page introduction, 29-page literature review, 16-page research participants and methodology, 34-page research findings, 40-page discussion, 1- page conclusion. - The thesis has 27 tables, 11 charts, 26 figures as well as231 references arranged in the order of appearance in the thesis. Chapter 1 LITERATURE REVIEW 1.1. Overview about Gastric cancer 1.1.1. Epidemiology According to GLOBOCAN in 2018, there were about 1 million new cases of GC. GC becomes the fifth leading malignancy after lung cancer, 3 breast cancer, colon cancer and prostate cancer. More than 70% of new cases are found in developing countries andhalf of the new cases in East Asia (mainly in China). Mortality caused by GC ranks the third position following lung cancer and colon cancer. The a ...