MINISTRY OF EDUCATION
AND TRAINING
MINISTRY OF DEFENCE
VIETNAM MILITARY MEDICAL UNIVERSITY
PHAN THI HIEN LUONG
STUDYING POLYMORPHISM OF TNF- -308 G>Aα AND
TGF- 1-509C>T βIN HEPATOCELLULAR CARCINOMA
PATIENTS WITH HBsAg POSITIVE
Specialty: INTERNAL MEDICINE
Code: 9 72 01 07
THE SUMMARY OF THE MEDICAL DOTORAL THESIS
HANOI – 2020
THIS DOCTORAL THESIS WAS COMPLETED
AT VIETNAM MILITARY MEDICAL UNIVERSITY
Scientific Instructors:
1. A/PROF. Nguyen Ba Vuong
2. A/PROF. Tran Viet Tu
1st Contradictor: A/PROF. Vu Van Khien
2nd Contradictor: PROF. Nong Van Hai
3rd Contradictor:A/PROF. Hoang Thanh Tuyen
The doctoral thesis will be reported to The Grading and
Examinations Committee hold at Vietnam Military Medical
University at
Searching for the dissertation at:
1. National Library
2. Vietname Military Medical University’s library
3. .............................................................................
INTRODUCTION
Hepatocellular carcinoma (HCC) is one of the common malignant
tumors globally with the main cause is chronic hepatitis B virus
(HBV) infection. This cancer has a poor prognosis with a short
survival time, due to limited early diagnosis.
The host's single nucleotide polymorphism (SNP) plays an
important role in determining the body's immune response to HBV
infection, affecting HCC formation.
Research on gene polymorphism helps stratify risk subjects,
improve early detection and treatment results. Recently, many studies
in the world have shown the influence of TNF- -308 G> Aα and TGF
1-509C>Tβ is associated with an increased HCC risk. The carriers
of A allele of TNF- - 308 G>Aα, T alleles of TGF 1-509 C>Tβ
increase the risk of HCC higher than the other carriers of alleles.
The polymorphisms influence HCC progression in controlling the
concentration of the corresponding cytokines. In the microbiological
environment, these cytokines interact, support and enhance the
effects of each other.
Vietnam is a country, located in the epidemic zone of hepatitis B
virus, having a high incidence of HCC with extremely serious
consequences.
Therefore, the thesis "Studying polymorphism of TNF- -308α
G>A and TGF- 1-509C>T in hepatocellular carcinoma patientsβ
with HBsAg positive" was conducted with two objectives.
1. Determining the frequency of genotype and allele of TNF-α
– 308 and TGF- 1-509β in HCC patients with HBsAg (+).
2. Analysing the association of TNF- -308, TGF- 1-509α β
polymorphism with risk of HCC and some clinical and subclinical
characteristics of HCC patients.
1
* New contributions of this doctoral thesis
- This is the first scientific study in Vietnam researching on
frequency of genotype, allele of TNF- -308 G>A, TGF- 1-509α β
C>T in healthy people, chronic hepatitis B and HCC with HBsAg
(+).
* TNF- – 308 G>Aα
+ The AA genotype only appeared in HCC group, which was
0.98%, the frequency of alleles of A TNF- - 308 G>A was low inα
healthy people, 5.4%, which was similar to Asian population.
+ The frequency of allele A in the healthy group, chronic
hepatitis B and HCC was 5.4%, 5.83% and 13.2%, respectively.
There was differences in the frequency of genotypes GG, GA and A
allele among HCC groups compared to healthy, chronic hepatitis B
groups.
* TGF– 1- 509 C>Tβ
+ The frequency of T allele in the healthy group, HBV and
HCC was 52.9%; 61.67% and 63.24%, respectively. There was
difference in the frequency of T allele in HCC and healthy groups.
- The study showed that A allele, genotype containing allele A of
TNF- -308α increased the risk of HCC compared with G allele and
genotype containing allele G. Alen T, genotype containing allele T of
TGF- 1-509β increased the risk of HCC compared with C allele and
genotype contain C allele. Two polymorphisms interacted
synergistically with each other increasing the risk of HCC.
* The doctoral thesis arrangement: This thesis contains 113
pages (without references and appendixes): Introduction: 02 pages,
Chapter 1 Overview: 31 pages, Chapter 2: Subjects and methods: 17
pages, Chapter 3 Results: 30 pages, Chapter 4 Discussion: 30 pages,
Conclusion: 02 pages, Recommendations: 01 page. It includes 46
tables, 23 figures, and 125 references (14 Vietnamese references and
111 English references).
2