2009 Vienna - European Society of Human Genetics

Cancer genetics
also studied.
In 317 cases, Rad50 revealed two variants (Q426R, Q1011R) predicted
to significantly disrupt protein structure or function. Q426R was
observed in two families. These exons and exon 5, the site of a Finnish
founder mutation, were analyzed in 600 controls: none of these
variants were found, though one additional likely deleterious variant,
N981I, was observed.
In 353 cases, Mre11 revealed two deleterious mutations (R576X,
R592X) and three likely benign variants (A492D, E497K, R576Q). One
probably deleterious mutation was observed among controls: W210G
concerns the same amino acid seen in ATLD patients homozygous for
W210C. No variants of NBN were observed in 250 cases. Our results
suggest that the R-M-N complex may contribute to breast cancer risk
in a small proportion of non-BRCA HBOC families. The observation of
deleterious mutations among the non-HBOC control group, however,
suggests that the oncogenic penetrance of such mutations may be
modest.
P06.041
codon 72 Polymorphism of P53 gene is Associated with an
increased susceptibility to Hepatocellular carcinoma in the
turkish Population
F. Eren1,2 , N. Tozun3 , F. Ture Ozdemir4 , H. Over Hamzaoglu5 , N. Imeryuz6 , O.
Ozdogan6 , E. Avsar6 ;
1Marmara University, Institute of Gastroenterology P.K. 53, İstanbul, Turkey,
2Marmara University, Instute of Health Sciences, Medical Biology and Genetics,
Istanbul, Turkey, 3Acıbadem University, School of Medicine, İstanbul, Turkey,
4 5 Marmara University Institute of Gastroenterology, İstanbul, Turkey, Marmara
University School of Medicine Gastroenterology Department, İstanbul, Turkey,
6Marmara University Institute of Gastroenterology and School of Medicine Gastroenterology
Department, İstanbul, Turkey.
Background and Aim: The P53 tumor suppressor gene plays role major
role in molecular mechanism of hepatocellular carcinoma (HCC)
being involved in cell cycle contol, the iniatiation of apoptosis and in
DNA repair. The effect of p53 Arg72Pro polymorphism on HCC risk
remains consistent due to ethnic differences of the populations studied.
We aim to evaluate the p53 Arg72Pro polymorphism on the susceptibility
of HCC in Turkish population. Method: In case-control study
including 54 patients with HCC and 112 cancer-free control subjects
matched for age, gender. P53 Arg72Pro polymorphism was genotyped
using PCR-RFLP. Fisher’s test with Woolf’s approximation was used
for statistical analysis. Results: The frequency of Pro allele was 49,1%
in HCC cases and 33,9 in controls, respectively. The Pro allele was
significantly associated with the presence of HCC (OR= 1,9, 95% [CI]=
1,17 - 2,99 p=0.01,). In addition, Pro/Pro homozygote genotype were
more frequent in patients with HCC than controls (OR, 2,9; 95%CI,
1.242-6.851 p= 0.02). We found that allele and genotype frequencies
of the control group for codon 72 of P53 are very similar to NCBI
SNP database records for the European population (RefSNP ID:rs
1042522).Conclusion: These findings indicate that the Pro allele of
p53 Arg72Pro polymorphism is associated with the presence of HCC
and Pro/Pro homozygote genotype is a potentially one of the genetic
risk factor for HCC in Turkish population. Carriage of Pro allele is a significant
predictor for HCC and therefore it can be used as a biomarker
for susceptibility to HCC.
P06.042
the Polymorphism of DNA repair gene XRcc3 thr241met is
Associated with an increased Risk of Hepatocellular carcinoma
in the turkish Population
F. Eren 1,2 , N. Tozun 3 , F. Ture Ozdemir 1 , H. Over Hamzaoglu 4 , N. Imeryuz 5 , O.
Ozdogan 5 , E. Avşar 5 ;
1 Marmara University Institute of Gastroenterology, İstanbul, Turkey, 2 Marmara
University, Instute of Health Sciences, Medical Biology and Genetics, Turkey,
3 Acıbadem University, İstanbul, Turkey, 4 Marmara University School of Medicine
Gastroenterology Department, İstanbul, Turkey, 5 Marmara University Institute
of Gastroenterology and School of Medicine Gastroenterology Department,
İstanbul, Turkey.
Background and Aim: Hepatocellular carcinoma (HCC) is associated
with HBV infection and chemical carcinogens (such as aflatoxin B1)
that induce DNA damage. In addition, genomic instability and DNA
repair play important role in hepatocarcinogenesis. we tested the hypothesis
that the polymorphism of DNA repair gene X-ray repair cross
complementing group 3 (XRCC3) Threonin (Thr)241Metionin (Met) is
associated with risk of developing HCC.
Method: Genomic DNA was extracted from peripheral blood cells of
42 patients with HCC and 105 cancer-free control subjects matched
for age, gender. XRCC3 Thr241Met genotypes were identified PCR-
RFLP. Fisher’s test with Woolf’s approximation was used for statistical
analysis.
Results: The frequencies of Thr allele was 83.7% in HCC cases and
55.7 in controls, respectively. The Thr allele was significantly associated
with the presence of HCC (OR, 4,09, 95% CI, 2.131-7.876
p