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,