الفهرس 
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Abstract
Breast cancer is the most common cancer in women and its impact on mortality and morbidity is significant and well documented. It is also the most common cause of death from cancer among women worldwide. About 10% of breast cancer is due to strong inherited risk conferred by a dominant gene mutation. Significant proportion of hereditary breast cancer is due to germline mutations in either of the two predisposing genes, BRCA1 and BRCA2.
A wide variation in the BRCA2 mutation spectrum and frequency has been reported for different populations. Some of the BRCA2 mutations represent founder mutations; founder mutations can provide a starting place for understanding of the public health impact of inherited predisposing genes.
The aim of this work is to assess the frequency of founder 6174delT and 999del5 mutations of BRCA2 gene in healthy females and breast cancer female patients in Qalubia Governorate and correlate them with the presence or absence of family history of breast &/ or ovarian cancer to allow identification of individuals at high risk. The study was carried out on fifty females from Qalubia divided as the following:
. Control group (Group І): Including twenty healthy females, subdivided into two subgroups:
Group Іa: Ten healthy females without a family history of breast &/or ovarian cancers.
Group Іb: Ten healthy females with a family history of breast &/or ovarian cancer.
. Breast cancer group (Group П):
Including thirty female patients attending general surgery department, Benha university hospital, subdivided into two subgroups:
Group Пa: Fifteen female patients without a family history of breast &/or ovarian cancers.
Group Пb: Fifteen female patients with a family history of breast &/or ovarian cancers.
Consents were taken from the subjects after being informed the aim of the study, full history was taken (Age, menstrual history, marital status, parity, lactation, contraception and family history). All patients included were diagnosed to have invasive breast carcinoma. 5ml of venous blood from each subject were collected on tube containing EDTA, the sample mixed well and stored at -80 for further processing. Regarding to the patient group, the histopathology of the lesions were studied, formalin fixed paraffin embedded sections of breast lesions were retrieved from the archives of department of histopathology, faculty of medicine, Benha University.
DNA was extracted from the blood according to the manufacturer instructions. Primers were designed for amplification of the founder mutations 999del5 and 6174delT in BRCA2 gene, exons 9 and 11 respectively. Detection of 6174delT founder mutation of exon 11 was carried out by digestion of amplified products of exon 11with BstXI restriction Endonuclease. Agarose gel electrophoresis was done using separated on 2% agarose gel and 100 bp DNA ladder; the bands were stained with ethidium bromide.
Detection of the other founder mutation 999del5 was done using 7.5% polyacrylamide gels and 50 bp DNA ladder, stained with ethidium bromide; the mutation was identified by the presence of an extra band as compared with the pattern in carriers of only the wild-type allele.
Statistical package for social sciences (SPSS) and Microsoft Office Excel were used for data processing and data analysis. Our results showed that there was no statistically significant difference among the studied groups regarding to age, age of menarche, lactation , parity and use of oral contraceptives, the percentage of family history of breast cancer is much more than the ovarian cancer; also this study showed that the percentage of the first degree relative with breast and/or ovarian cancer is extremely higher than that of the second degree relative in the control and breast cancer groups with family history. In this study, the frequency of 999del5 was 14%, confirming the founder effect of this mutation in Egyptian population.The other mutation screened in this study was the founder mutation 6174delT, we found two cases showing this founder mutation, both are from the patient group with family history.
The mutations found in this study were of heterozygous genotype, according to this study, there was statistically significant negative correlation between frequency BRCA2 gene mutations and female age in the studied groups, there was negative correlation between BRCA2 gene mutations and ER receptor, PR receptor and HER2/neu status (positivity and negativity) and positive correlation between gene mutations and the pathological grade of the tumor in patients with breast cancer groups with and without family history; however this correlation did not reach a significant level.