الفهرس 
acknowledgmentOnly 14 pages are availabe for public view
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Abstract
Breast cancer is one of the most common and important diseases affecting women.
One million females worldwide are diagnosed with breast cancer every year. Treatment of
I’ advanced breast cancer is often futile and disfiguring, making early detection is a high
. priority in medical management of the disease (Frolov et ai, 2002) ..
The risk factors for breast cancer include environmental, hormonal and genetic
factors (Gad et al. 2002). Genetic factors contribute to a small proportion of breast cancer
incidence, approximately 30% of them could be diagnosed before the age of thirty (Lux et
al, 2006). The majority of breast cancer result from somatic mutation but 5 % - 10 % of all
cases of breast cancer are inherited as the result of germline mutation in autosomal
dominant breast cancer susceptibility genes. Many genes have been found to increase
susceptibility to cancer and are also associated with familial breast cancer. These genes
include Breast Cancer types 1 (BRCAl), Breast cancer type2 (BRCA2). Ataxia-
Telangiectasia Mutated gene (A TM), phosphate and Tensin homolog (PTEN), and Tumor
protein 53k Dalton (P53). Several other less frequently occurring predisposing genes such
as the Androgen receptor gene (AR), and the Estrogen Receptor (ER) gene may be
involved but to a lesser extent (Gad et al, 2002 and Lux et al, 2006).
Carriers of these predisposing genes mutations have been evaluated as having a 90%
lifetime risk of breast cancer. BRCAl and BRCA2 mutations are accounting for up to 90%
of these predisposing genes. BRCA2 gene on chromosome 13q 1.2 is thought to be
responsible for an estimated one-third of familial female breast cancer and the majority of
hereditary male breast cancer (Wooster et ai, 1994, 1995; Ford and Easton, 1998).
The BRCA2 gene spans approximately 70 kb and is composed of 27 exons, which
encodes a protein of 3418 amino acids. BRCA2 is involved in homologous recombination
(Davies et al, 2001 and Moynahan et al, 2001) but is also suggested to play a role in
transcriptional regulation (Hughes et al, 2003) and cell cycle control (Marmorstein et al. 2001).
Predisposition to cancer is inherited as a dominant genetic trait, whereas the
predisposing allele generally behaves as a recessive allele in somatic cells. Thus, a single
inherited copy of the mutant allele causing predisposition, and loss or inactivation of the
wild type allele, complete one of the steps in progression toward malignancy. When
chromosome loss is observed in breast and ovarian tumors from patients who carry
BRCA2 predisposing alleles, the wild-type copy of BRCA2 is invariably lost while the
presumptive mutant allele is retained. This finding supports the hypothesis that BRCA2 is
a tumor suppressor gene and suggests that the functional BRCA2 protein is present in
normal breast and ovarian epithelium tissue and is altered, reduced, or absent in some
breast and ovarian tumors (Lux et al, 2006). It has been shown that ethnically different
populations exhibit different germline mutation spectra in the BRCAl and BRCA2 genes
(Liede et al, 2002 and verhooge et al, 2001).
A variety of different types of mutation has been found in the BRCA2 gene
presumably predisposing to development of cancer. The most common mutation of them is
a frameshift mutation at position 999 in exon9, involving a deletion of 5-bp and denoting
(999de1.5) mutation (Thorlacius et al, 1996). There are no previous publications on
BRCA2 mutation detection in the Egyptian population. The Identification and study of the
Egyptian mutations could facilitate early diagnosis and proper counseling for breast cancer.