Azribi et al.

BMC Cancer (2021) 21:1350

https://doi.org/10.1186/s12885-021-09094-8

RESEARCH Open Access

Prevalence of BRCA1 and BRCA2 pathogenic

sequence variants in ovarian cancer patients
in the Gulf region: the PREDICT study
Fathi Azribi1*, Ehab Abdou2, Emad Dawoud1, Mohamed Ashour2, Amgad Kamal3, Mohamed Al Sayed3 and
Ikram Burney4

Abstract
Background: Patients with pathogenic sequence variants (PSVs) in BRCA1/BRCA2 are at high risk of developing ovar-
ian cancer (OC). However, genetic testing for BRCA1/BRCA2 PSVs is still not a routine practice in the Middle East. With
the lack of epidemiological studies in the region, we aim to describe the prevalence of BRCA1/BRCA2 PSVs in patients
with OC across different countries in the Gulf region.
Methods: The PREDICT study was an observational, prospective, epidemiological study, which consecutively
recruited women with ovarian, primary peritoneal, and fallopian tube cancers from the following Gulf countries over
the period from July 2017 to July 2019; United Arab Emirates (UAE), Kuwait, and Oman. The study was approved by
the local ethics committee of participating centers. The BRCA1/BRCA2 PSVs were assessed by tissue genetic testing
using next-generation sequencing (NGS).
Results: A total of 105 women were included with a median age at diagnosis of 52 years (IQR 44.5 – 61.0). Nearly
11.4% of patients reported a family history of ovarian or breast cancer, while 4.7% of patients reported a family history
of other cancers. Most of the patients (70.3%) had advanced disease (FIGO stage III/IV) at presentation. Eighty-eight
patients (84%) were successfully tested for somatic BRCA1/BRCA2 PSVs. Fifteen patients (17%) were found to have
PSVs in either BRCA1, BRCA2, or both genes; of them, 10 patients (11.2%) had BRCA1 somatic PSVs alone, eight patients
(9.1%) had BRCA2 somatic PSVs, while three patients (2.9%) had both PSVs. Five patients with BRCA1/BRCA2 somatic
PSVs had germline PSVs tests, and three of them tested positive. Concerning treatment, 87.6% of patients received
perioperative chemotherapy and 6.6% as first-line palliative chemotherapy. Eighty-seven (82.9%) patients underwent
debulking surgery, with no residual disease in 42.5% of patients.
Conclusion: Our study showed that the prevalence of BRCA1/BRCA2 somatic PSVs in patients with OC is higher than
the reported global figures (2-8%). However, more studies are warranted to further elucidate the prevalence of BRCA1/
BRCA2 somatic and germline PSVs, as well as other relevant genetic alterations, to better understand their impact on
OC patient outcomes in Gulf countries.
Trial registration: NCT03​082976.
Keywords: Gynaecological oncology, Cancer genetics, Epidemiology

Introduction
Ovarian cancer is considered to be the eighth most com-
*Correspondence: [email protected]
1
Tawam Hospital, Al Ain, United Arab Emirates
mon cancer among females and the eighth cause of death
Full list of author information is available at the end of the article from cancer in women [1, 2], with a high mortality rate

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Azribi et al. BMC Cancer (2021) 21:1350 Page 2 of 8

(62.5%) and one of the worst prognoses among gyneco- consecutively from Kuwait Cancer Control Center
logic cancers [1, 3, 4]. Approximately 75% of women at (KCCC) in Kuwait, SQUH in Oman, and Tawam Hospi-
diagnosis presented with advanced disease status [5], tal in UAE over the period from July 2017 to July 2019.
which account for the poor prognosis of the disease [5, Female patients aged 18 years or older with histologi-
6]. In the Middle East, women with gynecological can- cally confirmed epithelial ovarian, primary peritoneal,
cers tend to seek medical advice very late in the course or fallopian tube cancers were eligible for the study. An
of their disease due to several factors, including stigma availability of paraffin-embedded archived tumor tis-
and the lack of awareness about reproductive health [7]. sue block or a minimum of twenty 10-μm sections (if a
Several risk factors are incorporated in the development block is not available) was also required. Patients with
of ovarian cancer, such as family history, indicating the previous tumors metastasizing to the ovary, patients
involvement of a genetic component in the development with secondary malignancies associated with ovar-
of this disease [8]. Accordingly, knowledge of the genetic ian cancer, patients diagnosed with other severe acute
susceptibility to ovarian cancer can be useful in preven- or chronic medical or psychiatric conditions were
tion efforts [9]. excluded from this study. Patients enrolled in this study
An important factor that contributes to ovarian can- signed an informed consent form (ICF) when meet-
cer susceptibility is mainly represented in BRCA1 and ing all inclusion criteria. Demographic and clinical
BRCA2 genes that are associated with different risks of characteristics data were collected from patient medi-
developing breast and ovarian cancers [9, 10]. Carriers of cal records of the hosting institutions. Archived tumor
inherited pathogenic sequence variants (PSVs) in BRCA1 samples were also obtained for the analysis of somatic
and BRCA2 are at an increased lifetime risk of develop- BRCA​ PSVs. Blood samples for genetic testing of ger-
ing ovarian cancer; recent reports highlighted that the mline BRCA​PSVs were sent to a central lab.
cumulative risk of ovarian cancer to age 80 years was 44% The analysis was performed on genomic DNA iso-
for BRCA1 carriers and 17% (95% CI, 11-25%) for BRCA2 lated from formalin-fixed paraffin-embedded (FFPE)
carriers [11]. The prevalence of BRCA1 and BRCA2 PSVs tissue from blocks or slides of the ovarian, fallopian
vary worldwide depending on several factors, including tube, or peritoneal serous carcinoma using the Tumor
the type of cancer and ethnic groups. Germline BRCA1 BRCA​ Analysis test. As a quality check, the portion of
and BRCA2 PSVs may be prevalent in up to 20% of epi- the tumor should have measured at least 5 × 5 mm and
thelial ovarian cancer. Somatic PSVs occur less frequently contain at least 20% tumor cellularity. In cases where
in BRCA1 and BRCA2 PSVs, with an estimated preva- blocks were not available, one 4-5 μm H&E slide and
lence of 2 and 8%, respectively [8, 12–14]. .There is a scar- four consecutive 10 μm unstained slides were accept-
city of data in the Middle East about the proportion of able. Patient DNA was extracted and purified from
ovarian cancer patients carrying these PSVs, and genetic the tumor specimen, assigned a unique bar-code for
testing is often not part of routine practice, despite its robotic-assisted continuous sample tracking, and sub-
potential for personalized medical treatment [15–18]. mitted for molecular testing.
This study estimated the prevalence of BRCA1 and The test consists of sequencing and large rearrange-
BRCA2 PSVs among female patients ≥18 years of age that ment analyses of the BRCA1 and BRCA2 genes using
are diagnosed with ovarian cancer, peritoneal cancer, and next-generation sequencing (NGS). For BRCA1, full
fallopian tube cancer in the Gulf region, with the aim of sequence determination of approximately 5.400 base-
informing clinical practice and improving clinical treat- pairs comprising 22 coding exons and approximately
ments in the future. It also describes the demograph- 750 introns were performed, excluding exons 1 and 4,
ics and clinical characteristics of patients with ovarian which are non-coding. For BRCA2, full sequence deter-
cancer. mination of approximately 10.200 base-pairs compris-
ing 26 coding exons and approximately 900 introns
Methods were performed, excluding exon 1, which is non-cod-
We followed STROBE guidelines for cross-sectional ing. Genomic DNA derived from the tumor was also
study during the preparation of the present manuscript. analyzed for large rearrangement analyses by NGS to
The study was approved by the local ethics committee of determine copy number abnormalities indicative of

analyzed using BRCAnalysis® (Myriad Genetics, Inc.,

participating centers. deletion or duplication PSVs. Somatic BRCA​ PSV was

Study design Salt Lake City, UT) kits on available tissue blocks from
This study is a multicenter, prospective, observational the subjects enrolled. Germline BRCA​ PSV using blood
epidemiologic study conducted across the Gulf region sample was used to detect if hereditary reason exists in
in UAE, Oman, and Kuwait. Patients were recruited those who were mutated.
Azribi et al. BMC Cancer (2021) 21:1350 Page 3 of 8

Study Subjects were classified according to treatment Table 1 Patients Demographics

status at the time of enrolment into treatment-experi- Patients’ Demographics N %
enced and treatment naïve subgroups.
Age (Mean, SD in years) 55.2 (12.0)
BMI (Mean, SD in kg/m2) 28.9 (5.7)
Statistical methods and data quality Smoking
Prevalence of BRCA​PSVs and associated 95% confidence Current or past smoker 3 2.9
intervals were estimated from the results of genetic tests. Never smoker 102 97.1
Appropriate descriptive statistics were used to summa- Race
rize the demographics and clinical characteristics of the Arabic 72 68.6
patients as well as disease management patterns. Sta- South Asian 22 21.0
tistical analysis was performed using IBM SPSS. It was East Asian 7 6.7
determined that the sample size of 120 would be suffi- Caucasian 1 1.0
cient to achieve a width of 15%, provided the prevalence African 3 2.9
of somatic BRCA​ PSVs is within the expected range of Nationality
15-20% [18]. PASS software was used to calculate the Egyptian 18 17.1
sample size required for our study. The potential impact Kuwaiti 18 17.1
of non-random assignment was reduced by attempting to Omani 13 12.4
recruit participants consecutively and by using consistent Emiratis 12 11.4
inclusion/exclusion criteria across all study sites. Pakistani 11 10.5
Filipinos 8 7.6
Indian 6 5.7
Results  ­Othersa 19 9.5
Demographic, clinical, and histological characteristics FIGO classification
In total, 105 consenting and eligible patients were IA 4 3.8
enrolled over 18 months. The median age at diagnosis IB 0 0
was 52 years (IQR 44.5 – 61.0). Approximately 68% of IC 14 13.3
patients were of Arab origin. High-grade serous carci- IIA 6 5.7
noma was the most reported histological type of tumors IIB 4 3.8
(46.7%), followed by unclassified serous carcinoma IIC 1 1.0
(23.8%) and low-grade serous carcinoma (2.9%). More IIIA 4 3.8
than half of the patients (54.3%) had advanced disease IIIB 5 4.8
(FIGO stage III/IV) at presentation. Besides, 87 (82.9%) IIIC 37 35.2
patients underwent debulking surgery, with no resid- IV 11 10.5
ual disease in 42.5%, optimal cytoreduction in 29.9%, Unknown/missing 10/9 18.1
and suboptimal cytoreduction in 25.3% of patients. The Histological Type
demographic, clinical, and histological characteristics of High grade serous carcinoma 49 46.7%
the patients are listed in Table 1. Low grade serous carcinoma 3 2.9%
Serous carcinoma (Not classified) 25 23.8%
Endometrioid carcinoma 8 7.6%
Family history Adenosarcoma 8 7.6%
A total of 10 (9.5%) patients reported having a total of Mixed carcinoma 4 3.8%
12 family members with a history of ovarian or breast Clear cell carcinoma 2 1.9%
cancer. Another three (2.9%) patients reported having a Carcinosarcoma 1 1.0%
total of five members with other types of cancer. Those Mucinous carcinoma 1 1.0%
patients with family history of ovarian or breast cancer Müllerian mixed tumor 1 1.0%
were younger than those who did not report any family Serous borderline tumor, micropapillary 1 1.0%
history of ovarian or breast cancer (48.9 versus 55.8 years variant
old respectively). As compared with patients who didn’t Missing 2 1.9%
report any family history of ovarian or breast cancer, a
Others were 3 from Syria, 2 from each of Bangladesh, Lebanon, Sudan, and
those who did were diagnosed at a younger age (46.3 vs Yemen, and 1 from each of United Kingdom, Afghanistan, Comoro islands, Iran,
Jordan, Palestine, Romania, and unknown origin
53.3 years). The distribution of the family history of can-
cers is present in Additional Table 1.
Azribi et al. BMC Cancer (2021) 21:1350 Page 4 of 8

Prevalence of BRCA​PSVs (Fig. 1). Among all 15 patients with the somatic PSVs,
Somatic BRCA​PSVs were present in 15 out of 88 subjects five patients were tested for germline PSVs. Among this
who had available test results (17.0, 95% CI, 9.9 to 26.6%). group, 3 (60%) had positive germline PSVs. The list of
The individual prevalence of BRCA1 and BRCA2 somatic PSVs position as per Gene Report is shown in Table 2.
PSVs among those with test results was 11.2% (95% CI, The clinical and histological features for those with
4.7 to 17.8%) and 9.1% (95% CI, 3.1 to 15.1%), respectively somatic BRCA1/BRCA2 compared with those who do

Fig. 1 Proportion of patients with BRCA1, BRCA2 PSVs

Table 2 List of PSVs Position as Per Gene Report

- The clinically significant variant NM_007294: c.1016delA was identified in exon 10 of the BRCA1 gene. No Pathogenic BRCA2 mutation or rearrang-
ment detected
- Pathogenic mutation in BRCA1 gene. c.140G > T (p.Cys47Phe)
- c.68_69del (p.Glu23Valfs*17)
- c.3436_3439 delTGTT P.CYS1146FS
- c.2269del (p.Val757Phefs*8) in BRCA 1
- BRCA1: c.4096G > C(p.Gly1366Arg), variant of uncertain significance BRCA2: c.10150C > T(p.Arg3384Ter), variant of uncertain significance
- BRCA1: c.2521C > T p.Arg841Trp BRCA1: c.1723G > A p.Glu575Lys
- BRCA1: c.237del (p.Phe79Leufs*9) BRCA2: None Detected
- BRCA1 mutation c.213-1A > T
- BRCA1 c.5107-5108delGAinsTG p.Glu1703Ter likely pathogenic
- c.4065_4065del
- BRCA1: pathogenic mutation detected. c.1716delA, p. (Glu572*) BRCA2: None Detected
- BRCA1 gene deleterious mutation c.4658del (p.Leu1553Cysfs*6)
- BRCA1 gene deleterious mutation c.1140dupG(p.Lys381 Glufs*3)
- C.512dupT (p.Gln172Thrfs*10)
- c.441 + 1G > A
- c.4065_4068del (p.Asn1355Lysfs*10)
- c.367C > T(p.Arg1203)
- c.3339 T > G, p.Tyr1113Ter pathogenic
- No Pathogenic BRCA1 or BRCA2 Mutation detected in tumor. Additional findings of BRCA2: c.353G > T (p.Arg118Leu) variant of uncertain significance
- c.6385G > T(pathogenic) p.Glu2129Ter
- Positive for a deleterious BRCA2 mutation in tumor c.7618-2A > G
- BRCA2 c.6815G > A p. (Arg2272Lys), variant may or may not modify protein function
- BRCA2 C.3201 del (p.Val1068 Tyrfs*9) gBRCA2 c.5290_5291delTC (p.Ser1764Lysfs*3) c.9019 > T(p.Arg3007*)
Azribi et al. BMC Cancer (2021) 21:1350 Page 5 of 8

not are presented in Table 3. Patients with somatic PSVs Table 3 Clinical and Histological Characteristics for those with
had slightly higher prevalence of family history of cancer and without somatic BRCA1 or BRCA2 PSVs
(13.3% versus 9.7%) and high-grade serous carcinoma Somatic BRCA1 or BCRA2
(66.7% versus 38.7%).
No (N = 72) Yes (N = 15)
n % n %
Discussion
The overall prevalence of somatic BRCA1/BRCA2 PSVs Age at diagnosis
in our study was 17% (95% CI, 9.9 to 26.6%). Accord- Mean ± SD 51.90 12.10 55.73 9.95
ing to previously published literature, the prevalence of Median (Q1-Q3) 51.50 44.50-60.0 56.00 47.0-64.0
BRCA1/BRCA2 PSVs ranges from 16 to 40% [13, 19–21], Family History
which reflects that the prevalence of BRCA1/BRCA2 Yes 7 9.7% 2 13.3%
PSVs in the Gulf region falls within the lower end in the No 65 90.3% 13 86.7%
global prevalence range. Several studies reported varia- Laterality
tion in the worldwide prevalence of BRCA1 and BRCA2 Bilateral 56 77.8% 10 66.7%
PSVs [13, 19–21]. This could be due to the ethnic differ- Unilateral 16 22.2% 5 33.3%
ences in the studied populations, barriers to access, dif- Allele
ferent tissue histology, and other latent variables. The Not Wild 17 23.6% 12 80.0%
Integrated genomic analyses of ovarian carcinoma study Wild 55 76.4% 3 20.0%
conducted through the Cancer Genome Atlas (TCGA) Stage at Diagnosis
Research Network reported a prevalence of 20% BRCA​ Unknown 4 5.6% 0 0.0%
PSVs in high-grade serous ovarian cancer samples. 0 1 1.4% 1 6.7%
Somatic BRCA​ PSVs were found in only 3% of patients I 13 18.1% 3 20.0%
[19]. Other studies reported an even higher overall preva- IIA 4 5.6% 2 13.3%
lence of BRCA​PSVs in ovarian cancer patients; In a study IIB 4 5.6% 1 6.7%
of 100 samples of ovarian carcinoma, the PSVs were IIIA 6 8.3% 1 6.7%
identified in 28% of samples [22]. However, other studies IIIC 26 36.1% 5 33.3%
found a lower prevalence of BRCA1/BRCA2 PSVs, rang- IV 14 19.4% 2 13.3%
ing from 8 to 14.1% [10, 23, 24]. Moreover, Koczkowska Tumor stage
et al. reported the overall prevalence of somatic BRCA1/ Unknown 4 5.6% 0 0.0%
BRCA2 PSVs was 4.1%, respectively [22]. Tis 1 1.4% 0 0.0%
Looking closely at individual BRCA​ PSVs, our study T1a 4 5.6% 0 0.0%
reported that BRCA1 and BRCA2 PSVs were detected T1b 1 1.4% 0 0.0%
in 11.2 and 9.1% of the patients, respectively. Variabil- T1c 9 12.5% 3 20.0%
ity in the prevalence of individual BRCA1 and BRCA2 T2a 4 5.6% 1 6.7%
PSVs (similar to the overall prevalence of BRCA1/BRCA2 T2b 5 6.9% 0 0.0%
PSVs) was also observed in similar studies. Previous T2c 1 1.4% 1 6.7%
reports showed that the prevalence of somatic BRCA1 T3a 11 15.3% 4 26.7%
and BRCA2 PSVs occurred in 2 and 8% of the patients, T3b 3 4.2% 1 6.7%
respectively [8, 12]. T3c 24 33.3% 4 26.7%
Most patients in our study were with advanced stages Tx 5 6.9% 1 6.7%
at diagnosis. This is consistent with the study by Heintz Node stage
et al., which reported that 75% of patients with ovar- Unknown 4 5.6% 0 0.0%
ian cancer were typically diagnosed at late stages (56.3% N0 17 23.6% 2 13.3%
stage III or higher; 44.6% stage III and 11.7% stage IV) N1 8 11.1% 4 26.7%
[25]. Another German study conducted on 1038 patients Nx 43 59.7% 9 60.0%
with ovarian cancer showed similar results (79% present- Metastatic stage
ing with FIGO III disease) [26]. The late presentation of Unknown 4 5.6% 0 0.0%
ovarian cancer in the Gulf region and the Middle East is M0 25 34.7% 5 33.3%
due to the stealthy nature of ovarian cancer, the stigma M1 6 8.3% 2 13.3%
of reporting gynecological symptoms, and lack of health Mx 37 51.4% 8 53.3%
awareness, especially among older women. FIGO classification
According to Stratton et al., and compared to women
IA 3 4.2% 0 0.0%
without familial history of ovarian cancer, women with a
Azribi et al. BMC Cancer (2021) 21:1350 Page 6 of 8

Table 3 (continued) emphasized on the importance of genetic counseling,

Somatic BRCA1 or BCRA2 guidelines for risk assessment, early detection, and put-
ting cost-effective screening programs in action [31].
No (N = 72) Yes (N = 15) This study has several strengths, and it opens the way
n % n % for future studies investigating clinical endpoints among
ovarian cancer patients in the Arabian Gulf region; one
IB 0 0.0% 0 0.0%
point of strength is the recruitment from multiple study
IC 11 15.3% 3 20.0%
sites across multiple countries in the Gulf region. This
IIA 4 5.6% 2 13.3%
study also highlighted the importance of tissue archiving
IIB 3 4.2% 1 6.7%
in a bio-bank / bio-repository and represents an encour-
IIC 1 1.4% 0 0.0%
aging example for oncology centers to start bio-banking.
IIIA 3 4.2% 0 0.0%
One potential limitation of our study is that, in absolute
IIIB 3 4.2% 1 6.7%
terms, the sample is relatively small, although this study
IIIC 24 33.3% 4 26.7%
recruited a substantial and sufficient sample size to con-
IV 5 6.9% 3 20.0%
duct all planned analyses. Another limitation was that
Unknown 15 20.8% 1 6.7%
only 84% (88 out of 105) of patients had genetic test-
ECOG Performance status
ing done; this was attributed to insufficient sample, low
0 47 65.3% 9 60.0%
sample quality, lack of tissue availability, or failed test-
1 17 23.6% 5 33.3%
ing. Also, the germline testing was limited to those with
2 5 6.9% 1 6.7%
somatic PSVs, so the prevalence of germline PSVs could
3 3 4.2% 0 0.0%
not be computed. More patients will need to be recruited
Tumor type
for future studies investigating longitudinal endpoints,
High grade serous carcinoma 29 38.7% 10 66.7%
such as survival. In addition to that, and although all
Low grade serous carcinoma 3 4.0% 0 0.0%
efforts possible were made in order to ensure that accu-
Serous carcinoma (Not classified) 20 26.7% 2 13.3%
rate and complete data is collected for each patient, the
Endometrioid carcinoma 5 6.7% 1 6.7%
extent to which it is practical to do so (for example, the
Adenosarcoma 5 6.7% 0 0.0%
completeness of electronic patient medical records) is not
Mixed carcinoma 4 5.3% 0 0.0%
known a priori. Another possible limitation in our study
Clear cell carcinoma 2 2.7% 0 0.0%
is that the collected information regarding family history
Carcinosarcoma 0 0.0% 1 6.7%
was obtained through a personal interview and was not
Mucinous carcinoma 1 1.3% 0 0.0%
confirmed by the medical records of family members in
Müllerian mixed tumor 1 1.3% 0 0.0% question or a formal cancer registry database. It is also
Serous borderline tumor, micro- 1 1.3% 0 0.0% worth mentioning that the Gulf region is characterized
papillary variant
by a mixed ethnic population with Arabic predominance
Unclassified 1 1.3% 1 6.7%
[32]. Data regarding parity were not collected as well.
Secondary malignancies were excluded, as the primary
objective of the study was to reflect the frequency of
family history are reported to have a higher risk of devel-
BRCA1/BRCA2 PSVs in primary ovarian cancer patients.
oping this disease [27]. This has been interpreted as a
However, excluding breast cancer cases might have intro-
hereditary susceptibility genetically transmitted across
duced bias to our findings. Finally, there is always a pos-
generations [28]. A study by Negri et al. confirms that a
sibility among observational studies such as this one that
family history of ovarian cancer in first-degree relatives
unaccounted variables may result in residual bias in the
increases the risk of ovarian cancer. A family history of a
planned analyses, though caution was taken when inter-
few other cancer sites, including breast, intestine, stom-
preting the final results.
ach, and lymphomas, was also directly associated with
ovarian cancer risk, and the OR was increased for fam-
ily history of any cancer [29]. A study in Saudi Arabia Conclusion
reported that 20.3% of cases had a positive family history Our study showed that somatic BRCA1/BRCA2 PSVs
of either breast or ovarian cancer in either first- or sec- prevalence in Gulf Countries is notably higher than the
ond-degree relatives. 32.5% of cases were early-onset (age reported global figures (2-8%). These results warrant
at diagnosis < 40 years) [30]. more detailed future studies with a larger number of
A recent study by Siraj et al. in 2019, conducted in patients and further evaluation of germline and somatic
the Middle East, reported that BRCA1 PSVs were sig- BRCA1/BRCA2 PSVs to better understand their impact
nificantly associated with positive family history and on ovarian cancer patient outcomes in Gulf countries.
Azribi et al. BMC Cancer (2021) 21:1350 Page 7 of 8

References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global
Abbreviations cancer statistics 2018: GLOBOCAN estimates of incidence and mor-
DNA: Deoxyribonucleic Acid; FFPE: Formalin-fixed paraffin-embedded; FIGO: tality worldwide for 36 cancers in 185 countries. CA Cancer J Clin.
The International Federation of Gynecology and Obstetrics; H&E: Hematoxylin 2018;68:394–424.
and Eosin; ICF: Informed consent form; KCCC : Kuwait Cancer Control Center; 2. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global
kg: Kilogram; NGS: Next-generation sequencing; m: Meter; OC: Ovarian cancer; Cancer Observatory: Cancer Today; 2018.
PREDICT: Prevalence of BRCA1 and BRCA2 Pathogenic Sequence Variants in 3. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer
Ovarian Cancer Patients in The Gulf Region; PSVs: Pathogenic sequence vari- in the world: epidemiology and risk factors. Int J Women’s Health.
ants; SD: Standard deviation; TCGA​: The Cancer Genome Atlas. 2019;11:287–99.
4. Coburn SB, Bray F, Sherman ME, Trabert B. International patterns and
trends in ovarian cancer incidence, overall and by histologic subtype. Int
Supplementary Information J Cancer. 2017;140:2451–60.
The online version contains supplementary material available at https://​doi.​ 5. SEER Cancer stat facts: ovarian cancer. National Cancer Institute. https://​
org/​10.​1186/​s12885-​021-​09094-8. seer.​cancer.​gov/​statf​acts/​html/​ovary.​html.
6. Clark TG, Stewart ME, Altman DG, Gabra H, Smyth JF. A prognostic model
for ovarian cancer. Br J Cancer. 2001;85:944–52.
Additional file 1: Table 1. Family history of Cancer. 7. Ortashi O. Gynecological cancer services in Arab countries: present
scenario, problems and suggested solutions. Asian Pac J Cancer Prev.
2013;14:2147–50.
Acknowledgments 8. Ramus SJ, Gayther SA. The contribution of BRCA1 and BRCA2 to ovarian
This study was sponsored by AstraZeneca, United Arab Emirates. We appreci- cancer. Mol Oncol. 2009;3:138–50.
ate all the efforts made by Clinart MENA in performing the biostatistics and 9. Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, et al.
manuscript writing. Association of type and location of BRCA1 and BRCA2 mutations with risk
of breast and ovarian cancer. JAMA. 2015;313:1347–61.
Authors’ contributions 10. Alsop K, Fereday S, Meldrum C, DeFazio A, Emmanuel C, George J, et al.
FA contributed to concept and design, literature search, clinical stud- BRCA mutation frequency and patterns of treatment response in BRCA
ies, statistical analysis, manuscript preparation, manuscript editing, and mutation-positive women with ovarian cancer: a report from the Austral-
manuscript review. EA, ED, MA, and IB contributed to literature search, clinical ian ovarian Cancer study group. J Clin Oncol. 2012;30:2654–63.
studies, statistical analysis, manuscript preparation, manuscript editing, and 11. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips K-A, Mooij TM, Roos-
manuscript review. AK and MA contributed to concept and design, definition Blom M-J, et al. Risks of breast, ovarian, and contralateral breast Cancer for
of intellectual content, literature search, clinical studies, data acquisition, data BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317:2402–16. https://​
analysis, statistical analysis, manuscript preparation, manuscript editing, and doi.​org/​10.​1001/​JAMA.​2017.​7112.
manuscript review. All authors reviewed the manuscript. The author(s) read 12. John EM, Miron A, Gong G, Phipps AI, Felberg A, Li FP, et al. Prevalence of
and approved the final manuscript. pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA.
2007;298:2869–76.
Funding 13. Hennessy BTJ, Timms KM, Carey MS, Gutin A, Meyer LA, Flake DD, et al.
This study was sponsored by AstraZeneca, United Arab Emirates. We appreci- Somatic mutations in BRCA1 and BRCA2 could expand the number of
ate all the efforts made by Clinart MENA in performing the biostatistics and patients that benefit from poly (ADP ribose) polymerase inhibitors in
manuscript writing. ovarian cancer. J Clin Oncol. 2010;28:3570–6.
14. Li W, Shao D, Li L, Wu M, Ma S, Tan X, et al. Germline and somatic muta-
Availability of data and materials tions of multi-gene panel in Chinese patients with epithelial ovarian
The datasets used and/or analysed during the current study available from the cancer: a prospective cohort study. J Ovarian Res. 2019;12:80.
corresponding author on reasonable request. 15. Trainer AH, Meiser B, Watts K, Mitchell G, Tucker K, Friedlander M. Moving
toward personalized medicine: treatment-focused genetic testing of
women newly diagnosed with ovarian cancer. Int J Gynecol Cancer.
Declarations 2010;20:704–16.
16. Nassar HR, Sallam YA, Darwish T, Elbassuiony MA. Clinicopathological, Epi-
Ethics approval and consent to participate
demiologic Characteristics and Treatment Outcomes of Ovarian Cancer
The study was approved by the local ethics committee of Ministry of Health,
Patients at NCI, Cairo University. EC Cancer. 2016:2(3):106–20.
Kuwait (Ref No. 1990), Sultan Qaboos University (SQUH), Oman (Ref No. MREC
17. Abdulrashid K, Alhussaini N, Ahmed W, Thalib L. Prevalence of BRCA
# 1441), and Tawam Hospital, UAE (Ref No. SA/SS/600). Patients enrolled in
mutations among hereditary breast and/or ovarian cancer patients
this study signed an informed consent form (ICF) when meeting all inclusion
in Arab countries: systematic review and meta-analysis. BMC Cancer.
criteria.
2019;19:256.
18. Ashour M, Shafik HE. Frequency of germline mutations in BRCA1 and
Consent for publication
BRCA2 in ovarian cancer patients and their effect on treatment outcome.
Not applicable.
Cancer Manag Res. 2019;11:6275–84.
19. Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F, et al. Integrated
Competing interests
genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.
Amgad Kamal and Mohamed Alsayed work for AstraZeneca; however, there
20. McAlpine JN, Porter H, Köbel M, Nelson BH, Prentice LM, Kalloger SE, et al.
is no conflict of interest. Dr. Fathi Azribi has received honoraria for Advisory
BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and pres-
board, as a speaker and travel, from AstraZeneca, Pfizer, Novartis, BMS, Amgen,
ence of immune cell infiltrates in ovarian high-grade serous carcinoma.
and MSD. The rest of the authors declare that they have no conflict of interest.
Mod Pathol. 2012;25:740–50.
21. Mafficini A, Simbolo M, Parisi A, Rusev B, Luchini C, Cataldo I, et al. BRCA
Author details
1 somatic and germline mutation detection in paraffin embedded ovarian
Tawam Hospital, Al Ain, United Arab Emirates. 2 Kuwait Cancer Control Center,
cancers by next-generation sequencing. Oncotarget. 2016;7:1076–83.
Kuwait City, Kuwait. 3 Medical Affairs Department, AstraZeneca, Dubai, United
22. Koczkowska M, Zuk M, Gorczynski A, Ratajska M, Lewandowska M,
Arab Emirates. 4 Sultan Qaboos University Hospital, Seeb, Oman.
Biernat W, et al. Detection of somatic BRCA1/2 mutations in ovarian
cancer – next-generation sequencing analysis of 100 cases. Cancer Med.
Received: 17 June 2021 Accepted: 23 November 2021
2016;5:1640–6.
Azribi et al. BMC Cancer (2021) 21:1350 Page 8 of 8

23. Chao A, Chang T, Lapke N, Jung S, Chi P, Chen C, et al. Prevalence and
clinical significance of BRCA1/2 germline and somatic mutations in
Taiwanese patients with ovarian cancer. Oncotarget. 2016;7:85529–41.
24. Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, et al. BRCA1
and BRCA2 mutations account for a large proportion of ovarian carci-
noma cases. Cancer. 2005;104:2807–16.
25. Heintz A, Odicino F, Maisonneuve P, Quinn M, Benedet J, Creasman W,
et al. Carcinoma of the ovary. Int J Gynecol Obstet. 2006;95:S161–92.
26. Keyver-Paik M-D, Abramian A, Domröse C, Döser A, Höller T, Friedrich M,
et al. Integrated care in ovarian cancer “IgV Ovar”: results of a German
pilot for higher quality in treatment of ovarian cancer. J Cancer Res Clin
Oncol. 2016;142:481–7.
27. Stratton JF, Pharoah P, Smith SK, Easton D, Ponder BA. A systematic review
and meta-analysis of family history and risk of ovarian cancer. Br J Obstet
Gynaecol. 1998;105:493–9.
28. Easton D, Peto J. The contribution of inherited predisposition to cancer
incidence. Cancer Surv. 1990;9:395–416.
29. Negri E, Pelucchi C, Franceschi S, Montella M, Conti E, Dal Maso L,
et al. Family history of cancer and risk of ovarian cancer. Eur J Cancer.
2003;39:505–10.
30. Bu R, Siraj AK, Al-Obaisi KAS, Beg S, Al Hazmi M, Ajarim D, et al. Identifica-
tion of novel BRCA founder mutations in middle eastern breast cancer
patients using capture and sanger sequencing analysis. Int J Cancer.
2016;139:1091–7.
31. Siraj AK, Bu R, Iqbal K, Siraj N, Al-Haqawi W, Al-Badawi IA, et al. Prevalence,
spectrum, and founder effect of BRCA1 and BRCA2 mutations in epithe-
lial ovarian cancer from the Middle East. Hum Mutat. 2019;40:729–33.
32. Altinoz A, Al Ameri M, Qureshi W, Boush N, Nair SC, Abdel-Aziz A. Clinico-
pathological characteristics of gene-positive breast cancer in the United
Arab Emirates. Breast. 2020;53:119–24.

Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.

Ready to submit your research ? Choose BMC and benefit from:

• fast, convenient online submission

• thorough peer review by experienced researchers in your field
• rapid publication on acceptance
• support for research data, including large and complex data types
• gold Open Access which fosters wider collaboration and increased citations
• maximum visibility for your research: over 100M website views per year

At BMC, research is always in progress.

Learn more biomedcentral.com/submissions