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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. |