الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 218 |  |  |
| | | from | 218 | | |
Abstract
Breast cancer is one of the most common malignancies and the most common cause of
tdeaths among women around worldwide. This is known to be the second deadlies
cancer among American women and the first deadly cancer among European
of%women .In Egypt, BC is the most common cancer in females accounting for 38.8
tient age,aall female cancers. Several risk factors for breast cancer were studied as p
eatingtgender, hormone therapy, the number of offspring, breastfeeding and differen
fectionnhabits, but other factors remain obscure and less known as oncogenic viral i
e disease andhand their role in initiating breast cancer and their effect on the path of t
.its prognosis upon treatment
• Our study focused on exploring relation between the presence of BRCA1/2 mutations
and some clinic-pathological characteristics which might impact the pathogenesis of
BC disease and establishing diagnostic tool like HRM for genetic counselling, which
will help when selecting treatment modalities for BC patients. Also we aimed at
evaluating frequency of HPV in different samples, and its association with some
clinical and pathological characteristics of BC disease as a possible indicator of BC
who are at high risk of development of severe disease.
• This study was conducted on 48 BC patients diagnosed and treated at the medical
oncology department, National Cancer Institute (NCI), Cairo University between July
2018 and December 2020. The inclusion criteria were young women less than 45 years
old suffering from breast cancer and didn’t receive any chemotherapy treatment before
surgery. Thirty normal control women without known oncological disease and with
comparable age were included as a control group.
English Summary
140
Briefly we can summarize our results in the following points:
• The presence of HPV DNA was detected by qualitative PCR assay in both serum and
leukocyte of the two studied groups. The total positivity in tissue and/or leukocyte
among BC patients and control group were 16/48 (33.3%) and 0/30 (0%), respectively.
HPV DNAemia was detected in 16/48 (33.3%) in tissue of BC patients, and in 0/30
(0.0%) of controls, while in Leukocytes, HPV DNA was detected in 16/48 (33.3%) and
in 0/30 (0.0%) of BC and control groups respectively.
• HPV DNA was detected in 16/48(33.3%) with median viral load 20500(1700-240000)
in tissues of BC patients group. Whereas in control HPV DNA was not detected 0/30
(0%) with median viral load 0 (0) in leukocyte of control group, without significance
difference between BC and control group in leukocyte.
• Tweleve different HPV genotypes were detected included high risk genotypes ((HPV
18 in 3 samples), (HPV45 in 2 sample), 70 and 52), low risk genotype (HPV11)
urodetected into only one sample along with 3 other genotypes (102, 114 and 151). F
dsamples showed no significant similarity with any sequence registered in the use
• Regarding presence of HPV DNAs by quantitative real time PCR an.dd atcalbinaisce-s
pathological parameters. HPV DNA was detected in 16/48(33.3%) with median viral
load 20500 copies/μl ranged from1700 copies/μl to 240000 copies/μl in tissues of BC
patients group. Moreover, there was no significant association between HPV viral load
and any of the demographic or pathological findings. HPV DNA viral load presence
and quantity was higher in patients with age ≤ 45 years (median: 19000.0 Copies/l,
range: 1700.0 Copies/l to 100000.0 Copies/l) than older patients.
• The study identified 40 and 54 different BRCA1 and BRCA2 mutations, respectively
mostly in the form of frame shift and stop codon mutations. Regarding, BRCA1, 14
pathogenic mutations were detected, exon10 and exon 9 showed to be the most
affected exons representing (c.C1612T (25%) and c.C1471T (22.9%), respectively.
For BRCA2, only five pathogenic mutations were identified, exon 11 and exon 14
English Summary
141
showed to be the most affected exons (cT4001A (6.25%) and c.7231delA (4.16%),
respectively.
• Regarding relation between BRCA1/2 genes mutations and clinic-pathological
parameters, BRCA1 and BRCA2 carriers were younger than non-carriers though not
significant (p=0.440). Regarding the tumor characteristics, BRCA1/2 carriers had large
tumor size (p=0.091), high tumor grade compared to non-carriers but without
significance (P=0.098). Micro-classifications positivity (60%) was also more
frequently among BRCA1/2 carrier than non-carrier (p= 0.082). Regarding detection
of HMTV and HPV, BRCA1/2 mutation carriers has a skew towards negative results
(P=<0.001 and 0.004, respectively).
• Variations in BRCA 1/2 genes in the selected exons by HRM assay to confirm our
results by NGS for establishing diagnostic tool like HRM for genetic counseling,
which will help when selecting treatment modalities for BC patient.
• Only two samples with high risk human Papillomavirus type (HPV45) carrying three
pathogenic deleterious mutations, one sample HPV45 with viral load 1×105 copies/μl
had two stop codon mutations(exon9:c.C1471T:p:Q491X and exon 10
c.C1612T:p:Q538X) in BRCA1 and another sample HPV45 with viral load 7.5×103
copies/μl had one stop codon mutation ( exon 10:c.C818A:p.S273X) in BRCA2,
respectively.
• BRCA1and or BRCA2 UVS were identified in all positive cases with HPV. BRCA1
UVS were identified in 5 (31.25%) out of 16 positive HPV in BC cases with sixteen
non synonymous mutations. However, Exon 9, 10, 14 and 15 were the most affected
exons. The most frequently detected UVS (c.G967A:P.V323I in exon 9) in one case,
(c.G1108A:P.V370I in exon 10) in one case, (c.G4558A:P.G150R in exon 14) and all
the mutations in the affected exons.
• Regarding BRCA2, UVS were identified in 16 (100%) out of all 16 positive HPV cases
with nine non synonymous mutations. Exons 11, 10, 14 and 27 were the most affected
English Summary
142
exons. The most frequently detected UVS (c.A6337C:p.N113H in exon 11) in eleven
cases, (c.C1694T:p.A565V in exon 10) in seven cases and (c.G9702A:p.M3234I in
exon 27) in two cases.
• c.A6337C:p.N113H & c.C1694T:p.A565V with UVS in BRCA2 occurred in a case
with two pathogenic deleterious mutations (c.C1471T:p.Q491X in exon 9 &
c.C1612T:p.Q534X in exon 10) as this case had high risk HPV type 45 with viral load
(1×105 copies/μl).
• We conclude from this study, the relation between the presence of BRCA1/2 mutations
and some clinic-pathological characteristics which might impact the pathogenesis of
BC disease and establishing diagnostic tool like HRM for genetic counseling, which
will help when selecting treatment modalities for BC patients. Also we evaluating the
presence ratio of HPV in breast cancer patients, and their association with some
clinical and pathological characteristics of BC disease as a possible indicator of breast
cancer who are at high risk of development of severe disease.