الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide,
it is rarely detected early. HCC is the commonest primary cancer of the liver. It is one of
the major causes of morbidity and mortality in the world. It represents the third leading
cause of cancer death in males and the fourth in females with more than 600000 deaths
per year.
HCC development is a multi-step process that involves establishment of chronic
HCV infection, persistent chronic hepatic inflammation, progressive liver fibrogenesis,
initiation of neoplastic clones accompanied by irreversible somatic genetic/epigenetic
alterations, and progression of the malignant clones in a carcinogenic tissue
microenvironment, and each step in the process could be a target for prevention of
HCC.
Human DNA repair mechanisms play an important role in the protection of the
genome against chemical carcinogens and ionizing radiations, these agents induce
mutations in DNA and promote malignancies such as leukemia, liver, thyroid, lung,
colon, and breast cancers. Altered DNA repair capacity due to gene mutations or
nucleotide substitutions can result in increased susceptibility to these cancers.
Excision repair cross complementation group 1 (ERCC1) is an important gene
involved in base excision repair of DNA. Single-nucleotide polymorphisms (SNPs) in
ERCC1 gene have been related to tumor susceptibility in gastric, lung, colorectal, and
ovarian cancers. This research aimed to study the clinical significance of rs 1046282
polymorphism of ERCC1 as a risk factor for HCC.
This study was conducted on 100 subjects classified into 3 groups: HCC group,
Cirrhosis group and Control group.
All participants were subjected to detailed history, full clinical examination,
liver function tests, viral markers, AFP and ultrasonography. Genotypes of rs1046282
(T/C) SNP in ERCC1 were evaluated via real-time PCR using Taqman allelic
discrimination.
Regarding AST, total and direct bilirubin, PT and INR, cirrhotic group and HCC
group were significantly higher than control group. Regarding ALT, HCC group was
significantly higher than control group and cirrhotic group. Regarding albumin, HCC
group was significantly lower than control group and cirrhotic group.
There was a significant difference between cirrhosis group and HCC group as
regards genotype distribution (p=0.021) as CC genotype was more represented in HCC
group than cirrhosis group.
Also, there was a significant difference between cirrhosis group and HCC group
as regards allele distribution (p=0.047) and C allele was more represented in HCC than
cirrhosis group. The CC genotype as well as C allele was significantly associated with
increased risk of HCC (OR =1.006, 2.08 respectively).
The CC genotypes displayed significant risk for HCC between HCC and non
HCC groups compared to TT genotype as reference group by 16 folds (p=0.001,
OR=16). The C allele displayed significant risk for HCC between HCC and non HCC
groups by 1.8 folds compared to T allele as reference group (p=0.043, OR=1.882).
The univariate analysis of the data showed that spleen size and the CC genotype
were the most independent risk factors for HCC. However, the multivariate analysis
revealed that the CC genotype of the ERCC1 gene (p= 0.031) was the most independent
risk factor for the development of HCC.