Targeted BRCA1/2 population screening among Ashkenazi Jewish individuals using a web-enabled medical model: An observational cohort study

Published:December 03, 2021DOI:



      This study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs).


      Across 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years.


      A total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing.


      Although continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      ACMG Member Login

      Are you an ACMG Member? Sign in for online access.


      Subscribe to Genetics in Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Nelson H.D.
        • Fu R.
        • Goddard K.
        • et al.
        U.S. Preventive Services Task Force Evidence Synthesis, formerly Systematic Evidence Reviews.
        in: Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Agency for Healthcare Research and Quality (US), Rockville, MD2013
        • Sigal B.M.
        • Munoz D.F.
        • Kurian A.W.
        • Plevritis S.K.
        A simulation model to predict the impact of prophylactic surgery and screening on the life expectancy of BRCA1 and BRCA2 mutation carriers.
        Cancer Epidemiol Biomarkers Prev. 2012; 21: 1066-1077
        • Drohan B.
        • Roche C.A.
        • Cusack Jr., J.C.
        • Hughes K.S.
        Hereditary breast and ovarian cancer and other hereditary syndromes: using technology to identify carriers.
        Ann Surg Oncol. 2012; 19: 1732-1737
      1. PDQ® Cancer Genetics Editorial Board. Cancer genetics risk assessment and counseling (PDQ®) - Health Professional Version. National Cancer Institute. Accessed September 15, 2020.

        • Cohen S.A.
        • Huziak R.C.
        • Gustafson S.
        • Grubs R.E.
        Analysis of advantages, limitations, and barriers of genetic counseling service delivery models.
        J Genet Couns. 2016; 25: 1010-1018
        • Hoskovec J.M.
        • Bennett R.L.
        • Carey M.E.
        • et al.
        Projecting the supply and demand for certified genetic counselors: a workforce study.
        J Genet Couns. 2018; 27: 16-20
        • Mandelker D.
        • Zhang L.
        • Kemel Y.
        • et al.
        Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline testing.
        JAMA. 2017; 318 (Published correction appears in JAMA. 2018;320(22):2381): 825-835
        • Offit K.
        • Tkachuk K.A.
        • Stadler Z.K.
        • et al.
        Cascading after peridiagnostic cancer genetic testing: an alternative to population-based screening.
        J Clin Oncol. 2020; 38: 1398-1408
        • Levy-Lahad E.
        • Lahad A.
        • King M.C.
        Precision medicine meets public health: population screening for BRCA1 and BRCA2.
        J Natl Cancer Inst. 2015; 107: 420
        • Roa B.B.
        • Boyd A.A.
        • Volcik K.
        • Richards C.S.
        Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2.
        Nat Genet. 1996; 14: 185-187
        • Struewing J.P.
        • Hartge P.
        • Wacholder S.
        • et al.
        The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.
        N Engl J Med. 1997; 336: 1401-1408
        • Anglian Breast Cancer Study Group
        Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group.
        Br J Cancer. 2000; 83: 1301-1308
        • Lieberman S.
        • Tomer A.
        • Ben-Chetrit A.
        • et al.
        Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral.
        Genet Med. 2017; 19 (Published correction appears in Genet Med. 2020;22(3):672): 754-762
        • Metcalfe K.A.
        • Poll A.
        • Royer R.
        • et al.
        Screening for founder mutations in BRCA1 and BRCA2 in unselected Jewish women.
        J Clin Oncol. 2010; 28: 387-391
        • Metcalfe K.A.
        • Poll A.
        • Royer R.
        • et al.
        A comparison of the detection of BRCA mutation carriers through the provision of Jewish population-based genetic testing compared with clinic-based genetic testing.
        Br J Cancer. 2013; 109: 777-779
        • Manchanda R.
        • Loggenberg K.
        • Sanderson S.
        • et al.
        Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial.
        J Natl Cancer Inst. 2015; 107: 379
        • Wiesman C.
        • Rose E.
        • Grant A.
        • Zimilover A.
        • Klugman S.
        • Schreiber-Agus N.
        Experiences from a pilot program bringing BRCA1/2 genetic screening to the US Ashkenazi Jewish population.
        Genet Med. 2017; 19: 529-536
        • Lieberman S.
        • Lahad A.
        • Tomer A.
        • Cohen C.
        • Levy-Lahad E.
        • Raz A.
        Population screening for BRCA1/BRCA2 mutations: lessons from qualitative analysis of the screening experience.
        Genet Med. 2017; 19: 628-634
        • Manchanda R.
        • Patel S.
        • Antoniou A.C.
        • et al.
        Cost-effectiveness of population based BRCA testing with varying Ashkenazi Jewish ancestry.
        Am J Obstet Gynecol. 2017; 217: 578.e1-578.e12
        • Daly M.B.
        • Pilarski R.
        • Yurgelun M.B.
        • et al.
        NCCN Guidelines Insights: genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 1.2020.
        J Natl Compr Canc Netw. 2020; 18: 380-391
        • Rajagopal P.S.
        • Nielsen S.
        • Olopade O.I.
        USPSTF Recommendations for BRCA1 and BRCA2 testing in the context of a transformative national cancer control plan.
        JAMA Netw Open. 2019; 2e1910142
        • Swink A.
        • Nair A.
        • Hoof P.
        • et al.
        Barriers to the utilization of genetic testing and genetic counseling in patients with suspected hereditary breast and ovarian cancers.
        Proc (Bayl Univ Med Cent). 2019; 32: 340-344
        • Borry P.
        • Cornel M.C.
        • Howard H.C.
        Where are you going, where have you been: a recent history of the direct-to-consumer genetic testing market.
        J Community Genet. 2010; 1: 101-106
        • Tandy-Connor S.
        • Guiltinan J.
        • Krempely K.
        • et al.
        False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.
        Genet Med. 2018; 20: 1515-1521
        • Horton R.
        • Crawford G.
        • Freeman L.
        • Fenwick A.
        • Wright C.F.
        • Lucassen A.
        Direct-to-consumer genetic testing.
        BMJ. 2019; 367: l5688
        • National Academies of Sciences, Engineering and Medicine
        Exploring the Current Landscape of Consumer Genomics: Proceedings of a Workshop.
        The National Academies Press, 2020
      2. Pace L, Tung N, Hamilton JG, et al. Challenges and opportunities in engaging primary care providers in BRCA testing: early results from the BFOR study. Paper Presented at: Society for General Internal Medicine Annual Meeting; May 8-11, 2019; Washington, DC.

        • Pace L.E.
        • Tung N.
        • Lee Y.S.
        • et al.
        Challenges and opportunities in engaging primary care providers in BRCA testing: results from the BFOR study.
        J Gen Intern Med. 2021; (Published online June 25, 2021)
        • LeCompte L.L.
        • Young S.J.
        Revised common rule changes to the consent process and consent form.
        Ochsner J. 2020; 20: 62-75
        • Daly M.B.
        • Pilarski R.
        • Axilbund J.E.
        • et al.
        Genetic/familial high-risk assessment: breast and ovarian, version 2.2015.
        J Natl Compr Canc Netw. 2016; 14: 153-162
        • Pace L.E.
        • Lee Y.S.
        • Tung N.
        • et al.
        Comparison of up-front cash cards and checks as incentives for participation in a clinician survey: a study within a trial.
        BMC Med Res Methodol. 2020; 20: 210
        • Kind A.J.H.
        • Buckingham W.R.
        Making neighborhood-disadvantage metrics accessible - the neighborhood atlas.
        N Engl J Med. 2018; 378: 2456-2458
      3. Area Deprivation Index V3.0. University of Wisconsin School of Medicine and Public Health. Accessed May 1, 2021.

      4. Eckstein Y. Genetic testing? Only when it will do no harm. AMI Living. Published December 28, 2016. Accessed August 26, 2020.

        • Lynce F.
        • Isaacs C.
        Population-based BRCA1/2 testing in Ashkenazi Jews: ready for prime time.
        J Natl Compr Canc Netw. 2016; 14: 809-812
        • Manchanda R.
        • Burnell M.
        • Gaba F.
        • et al.
        Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study.
        BJOG. 2019; 126: 784-794
        • Trepanier A.M.
        • Supplee L.
        • Blakely L.
        • McLosky J.
        • Duquette D.
        Public health approaches and barriers to educating providers about hereditary breast and ovarian cancer syndrome.
        Healthcare (Basel). 2016; 4: 19
        • Weitzel J.N.
        • Blazer K.R.
        • MacDonald D.J.
        • Culver J.O.
        • Offit K.
        Genetics, genomics, and cancer risk assessment: state of the art and future directions in the era of personalized medicine.
        CA Cancer J Clin. 2011; 61: 327-359
        • McGrath S.P.
        • Walton N.
        • Williams M.S.
        • Kim K.K.
        • Bastola K.
        Are providers prepared for genomic medicine: interpretation of direct-to-consumer genetic testing (DTC-GT) results and genetic self-efficacy by medical professionals.
        BMC Health Serv Res. 2019; 19: 844
        • Miller C.E.
        • Krautscheid P.
        • Baldwin E.E.
        • et al.
        Genetic counselor review of genetic test orders in a reference laboratory reduces unnecessary testing.
        Am J Med Genet A. 2014; 164A: 1094-1101