Skip to main content

BRCA1/2 potential founder variants in the Jordanian population: an opportunity for a customized screening panel


A founder variant is a genetic alteration, that is inherited from a common ancestor together with a surrounding chromosomal segment, and is observed at a high frequency in a defined population. This founder effect occurs as a consequence of long-standing inbreeding of isolated populations. For high-risk cancer predisposition genes, such as BRCA1/2, the identification of founder variants in a certain population could help designing customized cost-effective cancer screening panels. This advantage has been best utilized in designing a customized breast cancer BRCA screening panel for the Ashkenazi Jews (AJ) population, composed of the three BRCA founder variants which account for approximately 90% of identified BRCA alterations. Indeed, the high prevalence of pathogenic BRCA1/2 variants among AJ (~ 2%) has additionally contributed to make population-based screening cost-effective in comparison to family-history-based screening. In Jordan there are multiple demographic characteristics supporting the proposal of a founder effect. A high consanguinity rate of ~ 57% in the nineties of the last century and ~ 30% more recently is a prominent factor, in addition to inbreeding which is often practiced by different sub-populations of the country.

This review explains the concept of founder effect, then applies it to analyze published Jordanian BRCA variants, and concludes that nine pathogenic (P) and likely pathogenic (LP) BRCA2 variants together with one pathogenic BRCA1 variant are potential founder variants. Together they make up 43% and 55% of all identified BRCA1/2 alterations in the two largest studied cohorts of young patients and high-risk patients respectively. These variants were identified based on being recurrent and either specific to ethnic groups or being novel. In addition, the report highlights the required testing methodologies to validate these findings, and proposes a health economic evaluation model to test cost-effectiveness of a population-based customized BRCA screening panel for the Jordanian population. The aim of this report is to highlight the potential utilization of founder variants in establishing customized cancer predisposition services, in order to encourage more population-based genomic studies in Jordan and similar populations.

Peer Review reports


Basic definitions: founder effect, founder population and founder variant

When a new population is founded by individuals who are randomly withdrawn from an ancestral population and then allowed to undergo rapid growth, a so-called “Founder Population” with decreased genetic variation in comparison to the parental population is created [1]. This effect could also be observed in populations which practice inbreeding, and results in enrichment of founder variants within respective populations. The high prevalence of some autosomal recessive disorders within certain founder populations are classic examples of this effect, such as Tay-Sachs disease in Ashkenazi Jews (AJ) [2], Ellis-van Creveld Syndrome in the Amish [3], Cystic Fibrosis in the Hutterites [4] and Congenital Chloride Diarrhea in the Finnish [5]. This feature has allowed founder populations to become valuable sources for studying the prevalent disorders within them. In the field of cancer predisposition, founder populations have also allowed the identification of multiple ethnic-specific pathogenic variants of known autosomal-dominantly inherited disease-causing genes, which has exerted great implications on genetic screening in their respective populations (e.g. BRCA screening panel of the AJ [6], the Polish [7, 8] and the Chilean [9]).

BRCA founder variants: benefit of applying customized population-based screening

Breast cancer is the most common cancer worldwide, and it is estimated that up to ~ 15% of all cases are hereditary [10]. BRCA1/2 pathogenic/likely pathogenic (P/LP) germline variants are the most common underlying genetic causes, and they are known to be associated with high penetrance rates, aggressive pathological phenotypes and earlier age of onset [11]. Since identification of the BRCA1/2 genes around 30 years ago [12, 13], several other genes related to hereditary breast cancer with variable penetrance rates have been identified (e.g. TP3) [14], and genetic testing and counseling have become an integral part of routine clinical practice. Nevertheless, many experts are continuously calling for expanding current testing guidelines both horizontally by including more patients and vertically by expanding the panel of genes tested for [15, 16]. Mary-Claire King, who was the first to describe BRCA1, has suggested that genetic screening, of at least BRCA1/2, should be offered to every woman at around the age of 30 years, in order to detect healthy carriers prior to cancer onset [17]. Indeed, several groups have calculated that family-history-based screening for BRCA deleterious variants could miss around 50% of carriers in comparison to a population-based screening approach [18]. However, a systematic review of economic evaluations of population-based vs. family-history-based BRCA testing proved cost-effectiveness only in high and upper-middle income countries and those with prevalent gene mutations, while population-based genetic testing for low-middle income countries was limited by the cost of the testing [19]. AJ are considered the first population who have applied a population-based screening, based on a significantly favorable cost-utility analysis (CUA) of applying a customized BRCA screening panel (a discounted incremental cost-effectiveness ratio (ICER) of—£2,079/QALY (quality-adjusted life-years), which is way below the threshold of £20,000/QALY according to the NHS policy in the United Kingdom (UK)) [18]. Besides the income of the country and the cost of testing panel, there are two main factors contributing to making this approach particularly significantly cost-effective for the AJ, which also make it a promising health economic approach for the Jordanian population. First the customized AJscreening panel detecting the three founder BRCA1/2 variants [6], which make ~ 90% of all possible pathogenic variants among the AJ, and second the high frequency of BRCA1/2 carriers (~ 2% of the AJ population, as identified by the GCaPPS study) [20].

Similarly, identifying founder BRCA variants has also been employed to develop simple affordable testing strategies in other involved populations, such as in Poland, where three variants have been identified to contribute to ~ 90% of all BRCA variants [7, 21], and in Chile, where nine founder variants make 78% of all identified BRCA1/2 variants [9]. Similar to the AJ, both populations are considered relatively homogenous. While the majority of the Polish population are believed to come from the seven European Clan mothers, [22] the founder effect in Chile could be attributed to the dramatic reduction of population due to smallpox and wars with the Spanish creating the scarce founder population of limited genetic variability which inflated during the subsequent 300 years [9].

This report analyzes published Jordanian BRCA1/2 variants, taking into consideration the historical demographic characteristics of the Jordanian population which could support the founder effect proposal. The report then provides an insight how to employ these findings to develop a customized BRCA screening panel for the Jordanian population. Finally, it provides a road-map of further steps needed to prove the founder variants and to conduct a CUA of the customized panel with the aim of facilitating decision making on this regard for the policy makers of the Jordanian health sector.

Main text

Breast cancer care in Jordan

Similar to the global situation, breast cancer is the most common malignancy in Jordan accounting for 20.6% of cancers in Jordanians of both sexes and 39.4% of cancers among Jordanian women, with increasing figures by 69% during the past decade [23, 24]. Around 60% of diagnosed Jordanian women are treated at King Hussein Cancer center (KHCC). On the other hand, Al- Bashir Hospital is the largest hospital of the public sector treating a significant share of the remaining 40% of cases. According to limited published data, almost 10–15% of breast cancer occurrences are inherited with the most commonly identified genetic alterations in BRCA1/2. The results of BRCA1/2 genetic testing from Jordan have been published between the years 2018 and 2021 [23, 25,26,27,28], in addition to an old report of a smaller cohort dating back to 2004 [29]. Reports are only available from the two major mentioned centers. Since P/LP mutations of BRCA1/2 genes are associated with early onset breast cancer and/or high-risk features (HR), this review analyzes the results of the two largest published cohorts from KHCC including 616 young female patients (i.e. younger than 40 years) [26] and 500 patients with high-risk (HR) features (median age = 39 years) [28], together with the largest published cohort of 192 female patients with HR features from Al-Bashir hospital (mean age = 43.6 years) [23].

Potential Jordanian BRCA1/2 founder variants

Eighty (12.2%) patients of the first cohort, seventy-two (13%) of the second and twenty-nine (14.5%) of the third had a P/LP variant of BRCA1/2 [23, 26, 28]. The prevalence of P/LP BRCA1/2 gene mutations among the specific subgroup of triple negative (TN) disease was 33.9%, and it was 60% among patients with both TN disease and a family history of breast cancer as published by KHCC group [30]. There are sixteen recurrent variants (i.e. occurring in two or more patients) which were identified in these two cohorts, as summarized in Tables 1 and 2. Further analysis of these variants leads to the proposal that ten could be founder variants, including nine BRCA2 variants and a single BRCA1 variant. Significantly, this group composes 43%, 55% of all identified BRCA1/2 variants among the two studied cohorts from KHCC, while the percentage was not easy to calculate from the third cohort, as the paper has only provided the results of 16 of the 29 reported patients with P/LP variants of BRCA1/2 (table 3 of the original paper [23]). In addition to the observation that all of the identified ten variants are recurrent, four are Palestinian-specific, four are specific to European/Caucasian ethnicity, and two are novel. In addition, one of these novel variants co-occurred with another variant in several patients suggesting the possibility of them being inherited as part of a mutual allele (Table 1). BRCA2 c.2254_2257del p.(Asp752Phefs*19) is the most common variant, accounting for 11/55 (20%) BRCA2 variant findings in the cohort of young patients, 8/48 (16.7%) in the second cohort and 2/8 (25%) of the third cohort. This variant has only been reported previously in a Palestinian patient [31]. Furthermore, five (six) of the patients, additionally carry BRCA2 c.5351dup p.(Asn1784Lysfs*3) in the first (second) cohort (Table 1) [27]. Both variants are located in exon 11, and their co-occurrence has not been reported previously [32,33,34,35,36,37], suggesting that they may have been both inherited as part of a shared founder allele from a common Jordanian ancestor. It could be argued here, that only the first variant is a bona fide pathogenic one, as it may omit the effect of the second downstream variant by its truncating effect on the protein or by nonsense mediated RNA decay. The other novel variant was BRCA2 c.4222_4223del p.(Gln1408Argfs*5) occurring in 2/55 cases among young patients [26]. The fourth potential founder variant was a BRCA2 exon 5–11 duplication, which occurred in 8/55 [26] and 5/48 patients [28]. This variant has been previously reported for Christian Palestinians exclusively, with a frequency of 5/33 [38]. The other two identified Palestinian-specific variants were: BRCA2 c.6685G > T p.(Glu2229Ter), and BRCA2 c.6627_6634del p.(Ile2209Metfs*13). On the other hand, only one of the identified recurrent BRCA1 variants seems to be ethnic-specific, which is BRCA1 c.5123C > A p.(Ala1708Glu), that was identified in 2/25 [26] and 2/24 patients [28]. This variant is a known Mediterranean founder variant, and has been described in the Spanish [39], Sephardic Jews [40] and Hispanics [41] (Table 2). In order to understand how Palestinian and Mediterranean founder variants could be mutual with the Jordanian population, a few historical characteristics of the Jordanian population need to be understood.

Table 1 Recurrent pathogenic and likely pathogenic BRCA2 variants of Jordanian patients with breast cancer
Table 2 Recurrent pathogenic and likely pathogenic BRCA1 variants of Jordanian patients with breast cancer

Understanding the historical demographic characteristics of the Jordanian population that could have created a founder effect

Jordan is a home of about 10.8 million inhabitants, with a majority of Arabs (98%) [47]. There are two major well-mixed communal groups in the country: Jordanians who originally come from Jordan, which is the land laying East to Jordan River, and Jordanians of Palestinian origin, who mainly fled to the country as a consequence of Palestinian-Israeli wars in 1948 and 1967 [48]. Secondly, while 4% of Arabs in the country are Christians [47], Circassians and Chechens represent the biggest two ethnic minorities in Jordan, with estimated percentages of ~ 1% [49] and ~ 0.1% [50] of the Jordanian population respectively (Fig. 1). Inbreeding is a common practice of the latter three subpopulations, and disparity in the distribution of mtDNA haplotype frequencies among Jordanian Arabs, Circassians and Chechens was demonstrated by Al-Eitan et al. in 2019 [51]. In a similar vein, up to twice as high crude rates of breast cancer in Circassians and Chechens in comparison to Arab Jordanians were reported in 2013, with (95%CI) rate ratios of 2.1 (1.48, 2.72) and 1.81 (1.16, 2.85), respectively [52]. Secondly, mutual Mediterranean founder variants, could be attributed to historical migratory movements, trade activities, and other populations’ interactions that used to occur along the Mediterranean and the Black sea (Fig. 1) [53], which could explain the recurrence of the three European/Caucasian BRCA2 variants and the known Mediterranean BRCA1 founder variant. Thirdly, even though Al-Eitan’s study did not include analysis in respect to religion, the fact that the recurrent BRCA2 exon 5–11 duplication has only been previously reported among Christian Palestinians [38], together with the tendency of this subpopulation to get married to Jordanians or Palestinians of the same religion, most likely makes this variant a potential founder variant for the Christian Jordanian-Palestinian population. Finally, consanguinity is a very common practice all over the country. In 1990, it was estimated that 57% of marriages in Jordan were consanguineous [54]. Despite the downward trend of this figure over the years, it still contributes to 30% of marriages in the country [54], which supports the proposal of potential founder effect in the general Jordanian population, which could be indeed thought of as a whole population descending from a few families whose offspring had been breeding with their cousins over the ages.

Fig. 1
figure 1

Mapping historical migratory movements to Jordan from Chechnya and the North Caucasus, which contribute to the two big ethnic minorities of the country. The figure also illustrates the third minority of Christian Arabs, together with the relationship between Jordanians and Palestinians who fled to the country during Palestinian-Israeli wars and currently make about half of the population. In addition, the interaction of populations around the Mediterranean and the Black sea are illustrated

A roadmap for developing a customized panel for the Jordanian population

Development of a customized screening panel for the Jordanian population would start with proving that the proposed variants are true founder variants. There are two types of association studies used for this purpose: Haplotype Analysis and Identity By Descent (IBD) studies, both studies help identify the longer shared DNA segments among affected patients who harbor the same potential founder variants, or in other words help to prove that the variants have been inherited as part of a mutual founder allele coming from a common ancestor [55]. Based on the size of the shared allele, several computational tools could be applied to predict the variant age [56], which could then be correlated to potential historical events contributing to the creation of the founder effect. Having those founder variants confirmed would allow the development of a customized test for the Jordanian population, offering ‘targeted screening’ for the common ten BRCA1/2 variants for lesser costs and faster turnaround times than conventional NGS panel sequencing of the BRCA genes. The cost of this customized test needs to be well-identified by communication with candidate provider companies before proceeding with conducting the health economic evaluation of a population-based screening vs. family-history-based screening. In addition, various probabilities and costs should be actively identified by conducting several further dedicated studies. A suggested model for such a CUA could be learnt from the AJ experience, particularly the analysis conducted by Manchanda et al. [18]. It can be observed from this model, that in order to proceed with the analysis, the frequency of BRCA1/2 mutations among the Jordanian population needs to be identified. The GCaPPS study of AJ has calculated the prevalence by testing a random sample of 1034 healthy volunteers of the AJ of both genders [20]. Other probabilities needed for the analysis would include the likelihood of the uptake of the screening panel by Jordanian population once made available, and the likelihood of an identified carrier to undergo risk-reducing mastectomy (RRM), with or without risk-reducing salpingo-oophorectomy (RRSO), which could be estimated by conducting a Knowledge, Attitude, and Practice (KAP) survey. In the CUA conducted by Manchanda et al., a test uptake of 71% of the general population was assumed as estimated by the GCaPPS study, together with a 52% probability of undergoing RRM and a 55% probability of undergoing RRSO, based on previously conducted KAP surveys [57, 58]. In addition, several studies have been conducted to study the factors affecting the attitude of AJ toward uptake of prophylactic surgeries, which might help predict the attitude of other populations. Next step of the analysis would be estimating QALYs of each health state in the model by multiplying their utility weights by the survival in life years, where utility weights range from 1 for a perfect health and 0 for death. Needed utility weights are available in the literature [59,60,61,62]. Finally, the costs of breast cancer treatment and ovarian cancer treatment need to be actively assessed by calculating the costs of different stages of both diseases in Jordan. Having that all done would allow ICER calculation to decide on the cost utility of the intended customized screening panel.


To conclude, understanding the concept of a founder mutation has allowed implementing cost-effective policies for genetic testing and screening for carriers in respective populations. Population-based screening for BRCA carriers has been suggested by several experts in the field and has been shown to be cost-effective for middle and high-income countries. Jordan, as an upper-middle-income country, where 43–55% of all identified BRCA events are potential founder events, has a real opportunity to benefit of a customized BRCA screening panel to detect healthy carriers prior to costly disease treatment. Indeed, adopting such an early detection approach would certainly decrease the current estimated incidence of late diagnoses of breast cancer in the country, which makes ~ 12% of new cases (double the rate of developed countries) [15]. This is the first report highlighting the preponderance of BRCA1/2 founder variants in Jordan. It is also the first report explaining how the historical demographic characteristics of the country could have created a founder effect, which might have similarly affected other genes in Jordan and in neighboring countries of similar historical and demographic features. On the other hand, a few limitations of this study need to be addressed. The first is the frequencies of potential founder BRCA variants, which have been estimated from the largest two published cohorts from KHCC and the available cohort from Al-Bashir hospital. A more accurate calculation by combining the data of all tested patients at KHCC would help calculate frequencies more precisely. Secondly, a threshold of two or more patients is used in this report to define recurrent variants. No clinical data have been available to examine if the identified variants are coming from different families, which would have strengthened our proposal, especially for the variants of lowest frequencies. Nevertheless, six out of the ten identified variants would still meet an increased threshold of three or more patients, and four different variants occur in five or more patients. Lastly, no data have been available to support the proposal that the two co-occurring variants on exon 11 of BRCA2 gene are in cis orientation (i.e. on the same allele). Thirdly, as mentioned in the manuscript, it was difficult to calculate the prevalence of the shortlisted variants among the cohort from Al-Bashir hospital due to limited published data. Nevertheless, it was good to identify BRCA2 c.2254_2257del as the most common variant at KHCC and Al-Bashir hospital, despite the small numbers of the latter cohort. Finally, it has to be clearly stated that this report focuses on a population-based screening approach aiming at early detection of healthy carriers. Other non-BRCA1/2 genes associated with breast and/or ovarian cancer (in less than 6% of hereditary cases [14]), are targeted by NGS-based multigene panel diagnostics adopted for affected families, which is not the focus of this report.

Availability of data and materials

Not applicable.



Ashkenazi Jews




Likely pathogenic


Cost-utility analysis


Incremental cost-effectiveness ratio


Quality-adjusted life years


United Kingdom




Triple Negative


Identity By Descent


Risk-reducing mastectomy


Risk-reducing salpingo-oophorectomy


Knowledge, Attitude, and Practice


  1. Templeton AR. The reality and importance of founder speciation in evolution. BioEssays. 2008;30(5):470–9.

    Article  PubMed  Google Scholar 

  2. Myerowitz R, Costigan FC. The major defect in Ashkenazi Jews with Tay-Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase. J Biol Chem. 1988;263(35):18587–9.

    Article  CAS  PubMed  Google Scholar 

  3. Ruiz-Perez VL, Ide SE, Strom TM, Lorenz B, Wilson D, Woods K, et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000;24(3):283–6.

    Article  CAS  PubMed  Google Scholar 

  4. Zielenski J, Fujiwara TM, Markiewicz D, Paradis AJ, Anacleto AI, Richards B, et al. Identification of the M1101K mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and complete detection of cystic fibrosis mutations in the Hutterite population. Am J Hum Genet. 1993;52(3):609–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hoglund P, Haila S, Socha J, Tomaszewski L, Saarialho-Kere U, Karjalainen-Lindsberg ML, et al. Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. Nat Genet. 1996;14(3):316–9.

    Article  CAS  PubMed  Google Scholar 

  6. Shiri-Sverdlov R, Oefner P, Green L, Baruch RG, Wagner T, Kruglikova A, et al. Mutational analyses of BRCA1 and BRCA2 in Ashkenazi and non-Ashkenazi Jewish women with familial breast and ovarian cancer. Hum Mutat. 2000;16(6):491–501.

    Article  CAS  PubMed  Google Scholar 

  7. Gorski B, Jakubowska A, Huzarski T, Byrski T, Gronwald J, Grzybowska E, et al. A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int J Cancer. 2004;110(5):683–6.

    Article  CAS  PubMed  Google Scholar 

  8. Nguyen-Dumont T, Karpinski P, Sasiadek MM, Akopyan H, Steen JA, Theys D, et al. Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer? Genet Res (Camb). 2020;102:e6.

    Article  CAS  PubMed  Google Scholar 

  9. Alvarez C, Tapia T, Perez-Moreno E, Gajardo-Meneses P, Ruiz C, Rios M, et al. BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile. Oncotarget. 2017;8(43):74233–43.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Drohan B, Roche CA, Cusack JC Jr, Hughes KS. Hereditary breast and ovarian cancer and other hereditary syndromes: using technology to identify carriers. Ann Surg Oncol. 2012;19(6):1732–7.

    Article  PubMed  Google Scholar 

  11. Edaily S, Abdel-Razeq H. Management Strategies of Breast Cancer Patients with BRCA1 and BRCA2 Pathogenic Germline Variants. Onco Targets Ther. 2022;15:815–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182):66–71.

    Article  CAS  PubMed  Google Scholar 

  13. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990;250(4988):1684–9.

    Article  CAS  PubMed  Google Scholar 

  14. Hauke J, Horvath J, Gross E, Gehrig A, Honisch E, Hackmann K, et al. Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancer Med. 2018;7(4):1349–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Abdel-Razeq H. Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity! Oncol Rev. 2021;15(1):544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Moyer VA, Force USPST. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(4):271–81.

    Article  PubMed  Google Scholar 

  17. King MC, Levy-Lahad E, Lahad A. Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA. 2014;312(11):1091–2.

    Article  CAS  PubMed  Google Scholar 

  18. Manchanda R, Legood R, Burnell M, McGuire A, Raikou M, Loggenberg K, et al. Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing. J Natl Cancer Inst. 2015;107(1):380.

    Article  PubMed  Google Scholar 

  19. Meshkani Z, Aboutorabi A, Moradi N, Langarizadeh M, Motlagh AG. Population or family history based BRCA gene tests of breast cancer? A systematic review of economic evaluations. Hered Cancer Clin Pract. 2021;19(1):35.

    Article  PubMed  PubMed Central  Google Scholar 

  20. GCaPPS. Genetic cancer prediction through population screening 2008–2016. ISRCTN: International Standard Randomised Controlled Trial Number, Version 2.0. Available from: Accessed 30 June 2023.

  21. Kowalik A, Siolek M, Kopczynski J, Krawiec K, Kalisz J, Zieba S, et al. BRCA1 founder mutations and beyond in the Polish population: A single-institution BRCA1/2 next-generation sequencing study. PLoS ONE. 2018;13(7):e0201086.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Szubański K. Science in Poland: science for the society. 2019. Available from:,in%20Western%20Europe%2C%20especially%20in%20Spain%20and%20Portugal. Accessed 1  June 2023.

  23. Abu-Helalah M, Azab B, Mubaidin R, Ali D, Jafar H, Alshraideh H, et al. BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan. Sci Rep. 2020;10(1):17573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Abdel-Razeq H, Mansour A, Jaddan D. Breast Cancer Care in Jordan. JCO Glob Oncol. 2020;6:260–8.

    Article  PubMed  Google Scholar 

  25. Abdel-Razeq H, Tamimi F, Abujamous L, Edaily S, Abunasser M, Bater R, et al. Patterns and Prevalence of BRCA1 and BRCA2 Germline Mutations Among Patients with Triple-Negative Breast Cancer: Regional Perspectives. Cancer Manag Res. 2021;13:4597–604.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Abdel-Razeq H, Abujamous L, Abunasser M, Edaily S, Bater R. Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan. Sci Rep. 2021;11(1):14906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Abdel-Razeq H, Al-Omari A, Zahran F, Arun B. Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan. BMC Cancer. 2018;18(1):152.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Abdel-Razeq H, Abujamous L, Jadaan D. Patterns and Prevalence of Germline BRCA1 and BRCA2 Mutations among High-Risk Breast Cancer Patients in Jordan: A Study of 500 Patients. J Oncol. 2020;2020:8362179.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Atoum MF, Al-Kayed SA. Mutation analysis of the breast cancer gene BRCA1 among breast cancer Jordanian females. Saudi Med J. 2004;25(1):60–3.

    PubMed  Google Scholar 

  30. Vishnubalaji R, Abdel-Razeq H, Gehani S, Albagha OME, Alajez NM. Identification of a Gene Panel Predictive of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy Employing Transcriptomic and Functional Validation. Int J Mol Sci. 2022;23(18):10901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. National human genome institute. BIC BRCA2 data results 2022. last updated 2022. Available from: Accessed 3 March 2022.

  32. BRCA Exchange. The ENIGMA Consortium. 2022. Available from: Cited 20 Jan 2022.

    Google Scholar 

  33. Breast Cancer Information Core. National Human Genome Research Institute. 2022. Available from: Cited 20 Jan 2022.

    Google Scholar 

  34. GC-HBOC. German Consortium for Hereditary Breast and Ovarian Cancer. 2022. Available from: Cited 20 Jan 2022.

    Google Scholar 

  35. ClinVar [database]. National center for biotechnology information, national library of medicine. Retrieved from : Accessed 22 Jan 2022.

  36. COSMIC. Catalogue Of Somatic Mutations In Cancer. Version 90. Wellcome Trust Sanger Institute. Retrieved from: Accessed 20 Jan  2022.

    Google Scholar 

  37. dbSNP [database]. Single nucleotide polymorphism database. National Center for Biotechnology Information (NCBI), national library of medicine. Retrieved from : Accessed 20 Jan  2022.

  38. Reznick Levi G, Larom G, Ofen Glassner V, Ekhilevitch N, Sharon Swartzman N, Paperna T, et al. A recurrent pathogenic BRCA2 exon 5-11 duplication in the christian Arab population in Israel. Fam Cancer. 2021;20(4):309–14.

  39. Diez O, Osorio A, Duran M, Martinez-Ferrandis JI, de la Hoya M, Salazar R, et al. Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. Hum Mutat. 2003;22(4):301–12.

    Article  CAS  PubMed  Google Scholar 

  40. Sagi M, Eilat A, Ben Avi L, Goldberg Y, Bercovich D, Hamburger T, et al. Two BRCA1/2 founder mutations in Jews of Sephardic origin. Fam Cancer. 2011;10(1):59–63.

    Article  PubMed  Google Scholar 

  41. Torres D, Rashid MU, Gil F, Umana A, Ramelli G, Robledo JF, et al. High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Res Treat. 2007;103(2):225–32.

    Article  CAS  PubMed  Google Scholar 

  42. Salahat MA. Two Novel BRCA1 and BRCA2 mutations in Palestinian women affected with breast cancer. 2011.

    Google Scholar 

  43. Laitman Y, Friebel TM, Yannoukakos D, Fostira F, Konstantopoulou I, Figlioli G, et al. The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries. Hum Mutat. 2019;40(11):e1–23.

    Article  CAS  PubMed  Google Scholar 

  44. MASTERMIND [database]. A comprehensive cancer genomics database. GENOMENON. Retrieved from: Accessed 20 Jan 2022.

  45. Laitman Y, Borsthein RT, Stoppa-Lyonnet D, Dagan E, Castera L, Goislard M, et al. Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel. Breast Cancer Res Treat. 2011;127(2):489–95.

    Article  PubMed  Google Scholar 

  46. Zidan J, Zhou AY, van den Akker J, Laitman Y, Schayek H, Schnaider J, et al. Inherited predisposition to breast and ovarian cancer in non-Jewish populations in Israel. Breast Cancer Res Treat. 2017;166(3):881–5.

    Article  CAS  PubMed  Google Scholar 

  47. Deaprtment of statistics Jordan. Jordanian population estimate 2022. Retrieved from: Updated Jan 23, 2022. Accessed 3 Mar 2022.

  48. Brand LA. Palestinians and Jordanians: A Crisis of Identity. JPS. 1995;24(4):46–61 16 pages.

    Google Scholar 

  49. Sam Mcneil. Jordan royals’ Circassian guards a symbol of thriving minority. The Times of Israel. Published Jan 30 2016. Retrieved from: Accessed 20 Jan 2022.

  50. Jordanian Chechen Site. Immigration To Jordan 2022. Document of sukhna. Retrieved from: Accessed 20 Jan 2022.

  51. Khoury SA, Massad D. Consanguineous marriage in Jordan. Am J Med Genet. 1992;43(5):769–75.

    Article  CAS  PubMed  Google Scholar 

  52. Fathallah RM, Dajani R. Comparison of population based cancer incidence rates among Circassians, Chechans and Arabs in Jordan (1996–2005). Asian Pac J Cancer Prev : APJCP. 2013;14(10):6035–40.

    Article  PubMed  Google Scholar 

  53. Charoute H, Bakhchane A, Benrahma H, Romdhane L, Gabi K, Rouba H, et al. Mediterranean Founder Mutation Database (MFMD): Taking Advantage from Founder Mutations in Genetics Diagnosis, Genetic Diversity and Migration History of the Mediterranean Population. Hum Mutat. 2015;36(11):E2441–53.

    Article  CAS  PubMed  Google Scholar 

  54. Islam MM, Ababneh FM, Khan MHR. Consanguineous Marriage in Jordan: An Update. J Biosoc Sci. 2018;50(4):573–8.

    Article  PubMed  Google Scholar 

  55. Sticca EL, Belbin GM, Gignoux CR. Current Developments in Detection of Identity-by-Descent Methods and Applications. Front Genet. 2021;12:722602.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Walter+Eliza Hall. Institute of medical research.  Genetic mutation age simulator. Retrieved from: Accessed 1 Jan 2023.

  57. Evans DG, Lalloo F, Ashcroft L, Shenton A, Clancy T, Baildam AD, et al. Uptake of risk-reducing surgery in unaffected women at high risk of breast and ovarian cancer is risk, age, and time dependent. Cancer Epidemiol Biomarkers Prev. 2009;18(8):2318–24.

    Article  PubMed  Google Scholar 

  58. Manchanda R, Burnell M, Abdelraheim A, Johnson M, Sharma A, Benjamin E, et al. Factors influencing uptake and timing of risk reducing salpingo-oophorectomy in women at risk of familial ovarian cancer: a competing risk time to event analysis. BJOG. 2012;119(5):527–36.

    Article  CAS  PubMed  Google Scholar 

  59. Havrilesky LJ, Broadwater G, Davis DM, Nolte KC, Barnett JC, Myers ER, et al. Determination of quality of life-related utilities for health states relevant to ovarian cancer diagnosis and treatment. Gynecol Oncol. 2009;113(2):216–20.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Madalinska JB, Hollenstein J, Bleiker E, van Beurden M, Valdimarsdottir HB, Massuger LF, et al. Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol. 2005;23(28):6890–8.

    Article  PubMed  Google Scholar 

  61. NICE. Advanced breast cancer: diagnosis and treatment. 2017.

    Google Scholar 

  62. Peasgood T, Ward SE, Brazier J. Health-state utility values in breast cancer. Expert Rev Pharmacoecon Outcomes Res. 2010;10(5):553–66.

    Article  PubMed  Google Scholar 

Download references


Open Access funding enabled and organized by Projekt DEAL.

Author information

Authors and Affiliations



Conceptualization and identifying potential founder variants, O.A.; Reviewing identified BRCA variants in BRCA specific databases, C.Su and S.H.; Writing—original draft preparation, O.A.; Writing—review and editing, C.Su., S.H., S.P. and C.Sc.; Visualization, O.A. and C.Su.; All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Christian P. Schaaf.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

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 The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmad, O., Sutter, C., Hirsch, S. et al. BRCA1/2 potential founder variants in the Jordanian population: an opportunity for a customized screening panel. Hered Cancer Clin Pract 21, 11 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: