Cascade testing is the process of offering genetic counseling and testing to at-risk relatives of an individual who has been diagnosed with a genetic condition. It is critical for increasing the identification rates of individuals with these conditions and the uptake of appropriate preventive health services. The process of cascade testing is highly varied in clinical practice, and a comprehensive understanding of factors that hinder or enhance its implementation is necessary to improve this process. We conducted a systematic review to identify barriers and facilitators for cascade testing and searched PubMed, CINAHL via EBSCO, Web of Science, EMBASE, and the Cochrane Library for articles published from the databases’ inception to November 2018. Thirty articles met inclusion criteria. Barriers and facilitators identified from these studies at the individual-level were organized into the following categories: (1) demographics, (2) knowledge, (3) attitudes, beliefs, and emotional responses of the individual, and (4) perceptions of relatives, relatives’ responses, and attitudes toward relatives. At the interpersonal-level, barriers and facilitators were categorized as (1) family communication-, support- and dynamics-, and (2) provider-factors. Finally, barriers at the environmental-level relating to accessibility of genetic services were also identified. Our findings suggest that several individual, interpersonal and environmental factors may play a role in cascade testing. Future studies to further investigate these barriers and facilitators are needed to inform future interventions for improving the implementation of cascade testing for genetic conditions in clinical practice.
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Gupta S, Ahnen DJ, Chen L-M, Chung DC, Cooper G, Early DS, et al. NCCN guidelines Version 3. 2019 genetic/familial high-risk assessment: Colorectal [Internet]. [cited 2019 Dec 18]. 2019. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf.
Cascade Testing: Testing Women for Known Hereditary Genetic Mutations Associated With Cancer - ACOG [Internet]. [cited 2019 Dec 18]. https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/Cascade-Testing-Testing-Women-for-Known-Hereditary-Genetic-Mutations-Associated-With-Cancer.
Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. Executive summary familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients clinical guidance from the national lipid association expert panel on familial hypercholesterolemia background and rationale. J Clin Lipidol. 2011;5:1–8.
Beitsch PD, Whitworth PW, Hughes K, Patel R, Rosen B, Compagnoni G, et al. Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol. 2019;37:453–60.
Abul-Husn NS, Manickam K, Jones LK, Wright EA, Hartzel DN, Gonzaga-Jauregui C, et al. Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science. 2016;354:aaf7000.
Hampel H, De La Chapelle A. The search for unaffected individuals with lynch syndrome: do the ends justify the means? Cancer Prev Res. 2011;4:1–5.
Roberts MC, Dotson WD, DeVore CS, Bednar EM, Bowen DJ, Ganiats TG, et al. Delivery of cascade screening for hereditary conditions: a scoping review of the literature. Health Aff. 2018;37:801–8.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–12.
Covidence Knowledge Base [Internet]. [cited 2019 Oct 21]. https://support.covidence.org/help.
Schardt C, Adams MB, Owens T, Keitz S, Fontelo P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med Inf Decis Mak. 2007;7:16.
Golden SD, Earp JAL. Social ecological approaches to individuals and their contexts: twenty years of health education & behavior health promotion interventions. Health Educ Behav. 2012;39:364–72.
Nha HONG Q, Pluye P, Fàbregues S, Bartlett G, Boardman F, Cargo M, et al. MIXED METHODS APPRAISAL TOOL (MMAT) VERSION 2018 User guide.
Benson G, Witt DR, VanWormer JJ, Campbell SM, Sillah A, Hayes SN, et al. Medication adherence, cascade screening, and lifestyle patterns among women with hypercholesterolemia: Results from the WomenHeart survey. J Clin Lipidol. 2016;10:937–43.
Burns C, McGaughran J, Davis A, Semsarian C, Ingles J. Factors influencing uptake of familial long QT syndrome genetic testing. Am J Med Genet A. 2016;170a:418–25.
Hardcastle S, Legge E, Laundy C, Egan S, French R, Watts G, et al. Patients’ Perceptions and Experiences of Familial Hypercholesterolemia, Cascade Genetic Screening and Treatment. Int J Behav Med. 2015;22:92–100.
Ishii N, Arai M, Koyama Y, Ueno M, Yamaguchi T, Kazuma K, et al. Factors affecting encouragement of relatives among families with Lynch syndrome to seek medical assessment. Fam Cancer. 2011;10:649–54.
Lerman C, Hughes C, Trock BJ, Myers RE, Main D, Bonney A, et al. Genetic testing in families with hereditary nonpolyposis colon cancer. JAMA. 1999;281:1618–22.
Lieberman S, Lahad A, Tomer A, Koka S, BenUziyahu M, Raz A, et al. Familial communication and cascade testing among relatives of BRCA population screening participants. Genet Med. 2018;20:1446–54.
Maxwell SJ, Molster CM, Poke SJ, O’Leary P. Communicating familial hypercholesterolemia genetic information within families. Genet Test Mol Biomark. 2009;13:301–6.
McClaren BJ, Aitken M, Massie J, Amor D, Ukoumunne OC, Metcalfe SA. Cascade carrier testing after a child is diagnosed with cystic fibrosis through newborn screening: investigating why most relatives do not have testing. Genet Med. 2013;15:533–40.
Mesters I, Ausems M, Eichhorn S, Vasen H. Informing one’s family about genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): a retrospective exploratory study. Fam Cancer. 2005;4:163–7.
Montgomery SV, Barsevick AM, Egleston BL, Bingler R, Ruth K, Miller SM, et al. Preparing individuals to communicate genetic test results to their relatives: report of a randomized control trial. Fam Cancer. 2013;12:537–46.
Ormondroyd E, Oates S, Parker M, Blair E, Watkins H. Pre-symptomatic genetic testing for inherited cardiac conditions: a qualitative exploration of psychosocial and ethical implications. Eur J Hum Genet. 2014;22:88–93.
Pentz RD, Peterson SK, Watts B, Vernon SW, Lynch PM, Koehly LM, et al. Hereditary nonpolyposis colorectal cancer family members’ perceptions about the duty to inform and health professionals’ role in disseminating genetic information. Genet Test. 2005;9:261–8.
Campbell M, Humanki J, Zierhut H. A novel approach to screening for familial hypercholesterolemia in a large public venue. J Community Genet. 2017;8:35–44.
Raspa M, Edwards A, Wheeler A, Bishop E, Bailey D. Family communication and cascade testing for fragile X syndrome. J Genet Couns. 2016;25:1075–84.
Smart A. Impediments to DNA testing and cascade screening for hypertrophic cardiomyopathy and Long QT syndrome: a qualitative study of patient experiences. J Genet Couns 2010;19:630–9.
Stoffel EM, Ford B, Mercado RC, Punglia D, Kohlmann W, Conrad P, et al. Sharing genetic test results in Lynch syndrome: communication with close and distant relatives. Clin Gastroenterol Hepatol. 2008;6:333–8.
Suttman A, Pilarski R, Agnese DM, Senter L. “Second-class status?” insight into communication patterns and common concerns among men with hereditary breast and ovarian cancer syndrome. J Genet Couns. 2018;27:885–93.
Truong TH, Kim NT, Nguyen MNT, Pang J, Hooper AJ, Watts GF, et al. Homozygous familial hypercholesterolaemia in Vietnam: case series, genetics and cascade testing of families. Atherosclerosis. 2018;277:392–8.
Ulph F, Cullinan T, Qureshi N, Kai J. Parents’ responses to receiving sickle cell or cystic fibrosis carrier results for their child following newborn screening. Eur J Hum Genet. 2015;23:459–65.
Louter L, Defesche J, Roeters van Lennep J. Cascade screening for familial hypercholesterolemia: Practical consequences. Atheroscler Suppl. 2017;30:77–85.
van Maarle MC, Stouthard ME, Marang-van de Mheen PJ, Klazinga NS, Bonsel GJ. How disturbing is it to be approached for a genetic cascade screening programme for familial hypercholesterolaemia? Psychological impact and screenees’ views. Community Genet. 2001;4:244–52.
Van Rijn MA, De Vries BBA, Tibben A, Van Den Ouweland AMW, Halley DJJ, Niermeijer MF. DNA testing for fragile X syndrome: Implications for parents and family. J Med Genet. 1997;34:907–11.
Wurtmann E, Steinberger J, Veach PM, Khan M, Zierhut H. Risk communication in families of children with familial hypercholesterolemia: identifying motivators and barriers to cascade screening to improve diagnosis at a Single Medical Center. J Genet Couns. 2018;28:50–8.
Cheung EL, Olson AD, Yu TM, Han PZ, Beattie MS. Communication of BRCA results and family testing in 1,103 high-risk women. Cancer Epidemiol Biomark Prev. 2010;19:2211–9.
de Souza Silva PR, Jannes CE, Oliveira TGM, Gómez LMG, Krieger JE, Santos RD, et al. Predictors of family enrollment in a genetic cascade screening program for familial hypercholesterolemia. Arq Bras Cardiol. 2018;111:578–84.
Dilzell K, Kingham K, Ormond K, Ladabaum U. Evaluating the utilization of educational materials in communicating about Lynch syndrome to at-risk relatives. Fam Cancer. 2014;13:381–9.
Dugueperoux I, L’Hostis C, Audrezet MP, Rault G, Frachon I, Bernard R, et al. Highlighting the impact of cascade carrier testing in cystic fibrosis families. J Cyst Fibros. 2016;15:452–9.
Finlay E, Stopfer JE, Burlingame E, Evans KG, Nathanson KL, Weber BL, et al. Factors determining dissemination of results and uptake of genetic testing in families with known BRCA1/2 mutations. Genet Test. 2008;12:81–91.
Hagoel L, Dishon S, Almog R, Silman Z, Bisland-Becktell S, Rennert G. Proband family uptake of familial-genetic counselling. Psychooncology. 2000;9:522–7.
Hallowell N, Jenkins N, Douglas M, Walker S, Finnie R, Porteous M, et al. Patients’ experiences and views of cascade screening for familial hypercholesterolemia (FH): a qualitative study. J Community Genet. 2011;2:249–57.
van El CG, Baccolini V, Piko P, Cornel MC. Stakeholder views on active cascade screening for familial hypercholesterolemia. Healthcare. 2018;6:108.
Hallowell N, Jenkins N, Douglas M, Walker S, Finnie R, Porteous M, et al. A qualitative study of patients’ perceptions of the value of molecular diagnosis for familial hypercholesterolemia (FH). J Community Genet. 2017;8:45–52.
Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): A 32-item checklist for interviews and focus groups. Int J Qual Heal Care. 2007;19:349–57.
Suthers GK, Armstrong J, McCormack J, Trott D. Letting the family know: balancing ethics and effectiveness when notifying relatives about genetic testing for a familial disorder. J Med Genet. 2006;43:665–70.
Marks D, Thorogood M, Neil SM, Humphries SE, Neil HA. Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes. J Med Screen. 2006;13:156–9.
Sermijn E, Goelen G, Teugels E, Kaufman L, Bonduelle M, Neyns B, et al. The impact of proband mediated information dissemination in families with a BRCA1/2 gene mutation. J Med Genet. 2004;41:e23.
Sturm AC. The role of genetic counselors for patients with familial hypercholesterolemia. Curr Genet Med Rep. 2014;2:68–74.
This work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health through Grant KL2TR002490 to MCR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official position of the National Institutes of Health or the Centers for Disease Control and Prevention.
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Srinivasan, S., Won, N.Y., Dotson, W.D. et al. Barriers and facilitators for cascade testing in genetic conditions: a systematic review. Eur J Hum Genet 28, 1631–1644 (2020). https://doi.org/10.1038/s41431-020-00725-5