الفهرس 
CirrhosisOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) represents an international public
health concern as one of the most common cancers worldwide. It is the fourth
most common cause of cancer-related death worldwide and is the sixth
regarding incidence rate.
Angiogenesis is the process of new blood vessel creation from the
already existing ones. Angiogenesis is a very crucial process in both
physiological and pathological conditions including tumor growth, and it is
firmly regulated by several factors. Many pathological conditions, including
tumors, can lead to uncontrolled angiogenesis. Tumor-induced angiogenesis is
enabled by over-expression of proangiogenic factors, along with underexpression of anti-angiogenic factors, causing increased tumor vascular
density with abnormal vascular structure.
The vascular endothelial growth factor is among the most common proangiogenic factors. There are four VEGF isoforms (A, B, C, and D) in
addition to the placental growth factor (PlGF) encoded by related different
genes.
Vascular endothelial growth factors (VEGF) are a group of
angiogenesis-promoting proteins has a role in primary tumor growth, invasion
and metastasis associated with many cancer types like breast cancer, lung
cancer, renal cancer, prostate cancer and leukemia. VEGF is highly
polymorphic gene, and its promoter, 5’- and the 3’-untranslated region (UTR)
has a variety of Single nucleotide polymorphisms (SNPs) which found to be
associated with variations in VEGF protein production.
The aim of this work was the detection of VEGF gene polymorphism
(rs699947 and 1570360) in liver cirrhosis and HCC and its correlation with
control cases, among the Egyptians.
The study population consisted of two groups who were divided according to
genotyping for VEGFA gene polymorphism (rs699947 and rs1570360) into
another three groups.
The first group (rs699947)
included 122 subjects who were
divided into
? group (1) included 34 healthy subjects as a control group.
? group (2) included 24 Cirrhotic liver diagnosed patients.
? group (3) included 64 HCC diagnosed patients.
The second group (rs1570360) included186 subjects who were divided into
? group (1) included 80 healthy subjects as a control group.
? group (2) included 36 Cirrhotic liver diagnosed patients.
? group (3) included 70 HCC diagnosed patients.
Relevant clinical data were collected. Samples of peripheral venous
blood were collected using EDTA anticoagulant-containing tubes and other
aliquots for serum isolation. Basic laboratory tests were done including
complete blood count using Sysmex xp- 300AM automated hematology
analyzer, liver function tests including [alanine aminotransferase (ALT),
aspartate aminotransferase (AST), total bilirubin, direct bilirubin and
albumin], ?- fetoprotein (AFP) and hepatitis serology (hepatitis B surface
antigen [HBsAg]and hepatitis C virus antibodies [HCV Ab].
DNA extraction and purification, tetra Primer Polymerase Chain Reaction
(ARMS-PCR) was performed for genotyping. The results were evaluated
using UV transilluminator and digital photographs were captured.
Interestingly, the current study demonstrated that the AA and the AC
genotypes of VEGF (rs69947), in addition to A- allele frequency, were
lower in HCC compared with the cirrhotic group. It also showed that control
group had the least frequent A-allele followed by HCC while the cirrhotic
group showed the highest A- allele frequency. The CC (wild type) genotype
was the most frequent in HCC patients (56.2%), followed by the CA
(heterozygous mutant type) (31.6%) and the least frequent was the AA
(homozygous mutant type) (12.2%). Based on the presence of rs699947 in
the promotor region at ?2578, it was expected to influence the expression of
VEGF.
According to VEGF (rs1570360) the current study demonstrated that
the AA and the AG genotypes, in addition to A- allele frequency, weren’t
different in HCC compared with the cirrhotic group. Also we showed that
cirrhotic group had the least frequent A-allele followed by control while
HCC group showed the highest A- allele frequency. In the current study, the
GG (wild type) genotype was the most frequent in HCC patients (60.2%),
followed by the AG (heterozygous mutant type) (31.6%) and the least
frequent was the AA (homozygous mutant type) (8.2%).in Conclusions,
there was no significant risk for HCC development in Egyptian patients with
the presence of VEGF (rs699947) but the risk in the presence of VEGF
(rs1570360), is possible.