Top

Published in:

01-08-2014 | Next Generation Genetic Counseling

Lynch Syndrome Patients’ Views of and Preferences for Return of Results Following Whole Exome Sequencing

Authors: Kelly Hitch, Galen Joseph, Jenna Guiltinan, Jessica Kianmahd, Janey Youngblom, Amie Blanco

Published in: Journal of Genetic Counseling | Issue 4/2014

Abstract

Whole exome sequencing (WES) uses next generation sequencing technology to provide information on nearly all functional, protein-coding regions in an individual’s genome. Due to the vast amount of information and incidental findings that can be generated from this technology, patient preferences must be investigated to help clinicians consent and return results to patients. Patients (n = 19) who were previously clinically diagnosed with Lynch syndrome, but received uninformative negative Lynch syndrome genetic results through traditional molecular testing methods participated in semi-structured interviews after WES testing but before return of results to explore their views of WES and preferences for return of results. Analyses of interview results found that nearly all participants believed that the benefits of receiving all possible results generated from WES outweighed the undesirable effects. The majority of participants conveyed that relative to coping with a cancer diagnosis, information generated from WES would be manageable. Importantly, participants’ experience with Lynch syndrome influenced their notions of genetic determinism, tolerance for uncertain results, and family communication plans. Participants would prefer to receive WES results in person from a genetic counselor or medical geneticist so that an expert could help explain the meaning and implications of the potentially large quantity and range of complicated results. These results underscore the need to study various populations with regard to the clinical use of WES in order to effectively and empathetically communicate the possible implications of this new technology and return results.

Aktan-Collan, K., Mecklin, J. P., Jarvinen, H., Nystrom-Lahti, M., Peltomaki, P., Soderling, I., et al. (2000). Predictive genetic testing for hereditary non-polyposis colorectal cancer: Uptake and long-term satisfaction. Internal Journal of Cancer, 89(1), 44–50.CrossRef

Ambry Genetics. (2012). Exome test requisition, preverification, & consent form – proband. Retrieved from https://doi.org/www.ambrygen.com/sites/default/files/pdfs/forms/Exome_Req_Consent.pdf.

ACMG Board of Directors. (2012). Points to consider in the clinical application of genomic sequencing. Genetics in Medicine, 14(8), 759–761. doi:https://doi.org/10.1038/gim.2012.74.CrossRef

Bamshad, M. J., Ng, S. B., Bigham, A. W., Tabor, H. K., Emond, M. J., Nickerson, D. A., et al. (2011). Exome sequencing as a tool for mendelian disease gene discovery. Nature Reviews Genetics, 12, 745–754. doi:https://doi.org/10.1038/nrg3031.PubMedCrossRef

Bandura, A. (1982). Self-efficacy mechanism in human agency. American Psychologist, 37(2), 122–147. doi:https://doi.org/10.1037/0003-066X.37.2.122.CrossRef

Baylor College of Medicine Medical Genetics Laboratories. (2013). WESrequisiton. Retrieved from https://doi.org/www.bcm.edu/geneticlabs/index.cfm?PMID=21320.

Berg, B. L. (2001). Qualitative research methods for the social sciences (4th ed.). Boston: Allyn and Bacon.

Berg, J. S., Khoury, M. J., & Evans, J. P. (2011). Deploying whole genome sequencing in clinical practice and public health: Meeting the challenge on bin at a time. Genetics in Medicine, 13(6), 499–505.PubMedCrossRef

Bloss, C. S., Ornowski, L., Silver, E., Cargil, M., Vanier, V., Schork, N. J., et al. (2010). Consumer perceptions of direct-to-consumer personalized genomic risk assessments. Genetics in Medicine, 12(9), 556–566. doi:https://doi.org/10.1097/GIM.0b013e3181eb51c6.PubMedCrossRef

Burt, R. W., Cannon, J. A., David, D. S., Early, D. S., Ford, J. M., Giardiello, F. M., et al. (2013). National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology [Colorectal cancer screening]. Version 2.2013, NCCN.org.

Choi, M., Scholl, U. I., Ji, W., Liu, T., Tikhonova, I. R., Zumbo, P., et al. (2009). Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proceedings of the National Academy of Sciences. U.S.A., 106, 19096–19101.CrossRef

Dunning, D., Johnson, K., Ehrlinger, J., & Kruger, J. (2003). Why people fail to recognize their own incompetence. Current Directions in Psychological Science, 12(3), 83–87. doi:https://doi.org/10.1111/1467-8721.01235.CrossRef

Emory Genetics Laboratory (2012). EmExome Requisition and Consent Form. Retrieved from https://doi.org/genetics.emory.edu/egl/reqform/standard/exome.php.

Evans, J. P., Burke, W., & Khoury, M. (2010). The rules remain the same for genomic medicine: The case against “reverse genetic exceptionalism.” Genetics in Medicine, 12(6). doi: https://doi.org/10.1097/GIM.0b013e3181deb308.PubMedCrossRef

Foster, M. W., Mulvihill, J. J., & Sharp, R. R. (2009). Evaluating the utility of personal genomic information. Genetics in Medicine, 11(8), 570–574. doi:https://doi.org/10.1097/GIM.0b013e3181a2743e.PubMedCrossRef

Gaff, C. L., & Bylund, C. L. (2010). Family communication about genetics: Theory and practice. New York: Oxford University Press.

Gould, W. A., & Heine, S. J. (2012). Implicit essentialism: genetic concepts are implicitly associated with fate concepts. PLoS One, 7(6), e38176. doi:https://doi.org/10.1371/journal.pone.0038176.PubMedPubMedCentralCrossRef

Green, R. C., Berg, J. S., Berry, G. T., Biesecker, L. G., Dimmock, D. P., Evans, J. P., et al. (2012). Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genetics in Medicine, 14(4), 405–410.PubMedPubMedCentralCrossRef

Green, R. C., Berg, J. S., Grody, W. W., Kalia, S. S., Korf, B. R., Martin, C. L., et. al. (2013). ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. American College of Medical Genetics and Genomics. Retrieved from https://doi.org/www.acmg.net/docs/ACMG_Releases_Highly-Anticipated_Recommendations_on_Incidental_Findings_in_Clinical_Exome_and_Genome_Sequencing.pdf.

Grillo, E., Lo Rizzo, C., Bianciardi, L., Bizzarri, V., Baladassarri, M., Spiga, O., et al. (2013). Revealing the complexity of a monogenic disease: rett syndrome exome sequencing. PLoS One, 8(2), e56599. doi:https://doi.org/10.1371/journal.pone.0056599.PubMedPubMedCentralCrossRef

Guiltinan, J. S., Hitch, K., Hechter, E., Youngblom, J., & Blanco, A. (2013). Application of whole exome sequencing to mine for novel genes associated with Lynch syndrome. Unpublished manuscript.

Hadley, D. W., Jenkins, J., Dimond, E., Nakahara, K., Grogan, L., Liewehr, D. J., et al. (2003). Genetic counseling and testing in families with hereditary nonpolyposis colorectal cancer. Archives of Internal Medicine, 163(5), 573–582. doi:https://doi.org/10.1001/archinte.163.5.573.PubMedCrossRef

Haimovich, A. D. (2011). Methods, challenges, and promise of next-generation sequencing in cancer biology. Yale Journal of Biology and Medicine, 84, 439–446.PubMedPubMedCentral

Hsieh, H., & Shannon, S. E. (2005). Three approaches to qualitative content analysis. Qualitative Health Research, 15(9), 1277–1288. doi:https://doi.org/10.1177/1049732305276687.CrossRefPubMed

Jamal, S. M., Yu, J. H., Chong, J. X., Dent, K. M., Conta, J. H., Tabor, H. K., et al. (2013). Practices and policies of clinical exome sequencing providers: Analysis and implications. American Journal of Medical Genetics, 161(5), 935–950. doi:https://doi.org/10.1002/ajmg.a.35942.CrossRef

Kruger, J., & Dunning, D. (1999). Unskilled and unaware of it: How difficulties in recognizing one’s own incompetence lead to inflated self-assessments. Journal of Personality and Social Psychology, 77(6), 1121–1134. doi:https://doi.org/10.1037//0022-3514.77.6.1121.PubMedCrossRef

Ku, C. S., Cooper, D. N., Iacopetta, B., & Roukos, D. H. (2012). Integrating next-generation sequencing into the diagnostic testing of inherited cancer predisposition. Clinical Genetics, 83(1), 2–6.PubMedCrossRef

Lagerstedt-Robinson, K., Liu, T., Vandrovcova, J., Halvarsson, B., Clendenning, M., Frebourg, T., et al. (2007). Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. Journal of the National Cancer Institute, 99(4), 291–299. doi:https://doi.org/10.1093/jnci/djk051.PubMedCrossRef

Lau, R. R. (1982). Origins of health locus of control beliefs. Journal of Personality and Social Psychology, 42(2), 322–334. doi:https://doi.org/10.1037//0022-3514.42.2.322.PubMedCrossRef

Lemke, A. A., Bick, D., Dimmock, D., Simpson, P., & Veith, R. (2012). Perspectives of clinical genetics professionals toward genome sequencing and incidental findings: a survey study. Clinical Genetics, 1–7. doi: https://doi.org/10.1111/cge.12060.PubMedPubMedCentralCrossRef

Lindor, N. M., Petersen, G. M., Hadley, D. W., Kinney, A. Y., Miesfeldt, S., Lu, K. H., et al. (2006). Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. The Journal of the American Medical Association, 296(12), 1507–1517.PubMedCrossRef

Majewski, J., Schwartzentruber, J., Lalonde, E., Montpetit, A., & Jabado, N. (2011). What can exome sequencing do for you? Journal of Medical Genetics, 48, 580–589. doi:https://doi.org/10.1136/jmedgenet-2011-100223.PubMedCrossRef

Murphy, J., Scott, J., Kaufman, D., Geller, G., LeRoy, L., & Hudson, K. (2008). Public Expectations for Return of Results from Large-Cohort Genetic Research. The American Journal of Bioethics, 8(11), 36–43. doi:https://doi.org/10.1080/15265160802513093.PubMedCrossRef

Mvundura, M., Grosse, S. D., Hampel, H., & Palomaki, G. E. (2010). The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genetics in Medicine, 12(2), 93–104. doi:https://doi.org/10.1097/GIM.0b013e3181cd666c.PubMedCrossRef

Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., et al. (2010). Exome sequencing identifies the cause of a mendelian disorder. Nature Genetics, 42(1), 30–35. doi:https://doi.org/10.1038/ng.499.PubMedCrossRef

Park, C. L., & Gaffey, A. E. (2007). Relationships between psychosocial factors and health behavior change in cancer survivors: An integrative review. Annals of Behavioral Medicine, 34(2), 115–134. doi:https://doi.org/10.1007/BF02872667.PubMedCrossRef

Parrott, R., & Smith, R. A. (2013). Defining genes using “blueprint” versus “instruction” metaphors: Effects for genetic determinism, response efficacy, and perceived control. Journal of Health Communication. doi:https://doi.org/10.1080/10410236.2012.729181.PubMedCrossRef

Schneider, K. A. (2012). Counseling about cancer: Strategies for genetic counseling. Hoboken: Wiley-Blackwell.

Singleton, A. B. (2011). Exome sequencing: a transformative technology. Lancelet Neurology, 10, 942–946.CrossRef

Shalowitz, D. I., & Miller, F. G. (2008). Communicating the results of clinical research to participants: Attitudes, practices, and future directions. Plos Medicine, 5(5), 714–720.CrossRef

Sobel, S. K., & Cowan, D. B. (2000). Impact of genetic testing for Huntington’s disease on the family system. American Journal of Medical Genetics, 90(1), 49–59.PubMedCrossRef

Tabor, H. K., Stock, J., Brazg, T., McMillin, M. J., Dent, K. M., Yu, J. H., et al. (2012). Informed consent for whole genome sequencing: A qualitative analysis of participant expectations and perceptions of risks, benefits and harms. American Journal of Medical Genetics, 158(Part A), 1310–1319.CrossRef

Townsend, A., Adam, S., Birch, P. H., Lohn, Z., Rosseau, F., & Friedman, J. M. (2012). “I want to know what’s in Pandora’s box”: Comparing stakeholder perspectives on incidental findings in clinical whole genomic sequencing. American Journal of Medical Genetics, 158(Part A), 2519–2525.CrossRef

Uhlmann, W. R., Schuette, J. L., & Yashar, B. M. (2009). A guide to genetic counseling (2nd ed.). Hoboken: Wiley-Blackwell.

Vernon, S. W., Gritz, E. R., Peterson, S. K., Perz, C. A., Marani, S., Amos, C. I., et al. (1999). Intention to learn results of genetic testing for hereditary colon cancer. Cancer Epidemiology, Biomarkers & Prevention, 8, 353–360.

Weil, J. (2000). Psychosocial genetic counseling. New York: Oxford University Press.

Worthey, E. A., Mayer, A. N., Syverson, G. D., Helbling, D., Bonacci, B. B., Decker, B., et al. (2011). Making a definitive diagnosis: Successful clinical application of WES in a child with intractable inflammatory bowel disease. Genetics in Medicine, 13(3), 255–262.PubMedCrossRef

Yu, J. H., Crouch, J., Jarnal, S. M., Tabor, H. K., & Bamshad, M. J. (2013). Attitudes of African Americans toward return of results from exome and whole genome sequencing. American Journal of Medical Genetics, 9999(Part A), 1–9.

Title: Lynch Syndrome Patients’ Views of and Preferences for Return of Results Following Whole Exome Sequencing
Authors: Kelly Hitch
Galen Joseph
Jenna Guiltinan
Jessica Kianmahd
Janey Youngblom
Amie Blanco
Publication date: 01-08-2014
Publisher: Springer US
Published in: Journal of Genetic Counseling / Issue 4/2014
Print ISSN: 1059-7700
Electronic ISSN: 1573-3599
DOI: https://doi.org/10.1007/s10897-014-9687-6

At a glance: The STEP trials

Springer Medicine

Lynch Syndrome Patients’ Views of and Preferences for Return of Results Following Whole Exome Sequencing

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2014

Stakeholders’ Opinions on the Implementation of Pediatric Whole Exome Sequencing: Implications for Informed Consent

Next Generation Genetic Counseling: Introduction to the Special Issue

The Incorporation of Predictive Genomic Testing into Genetic Counseling Programs

Cancer Risk Assessment Using Genetic Panel Testing: Considerations for Clinical Application

The Ophthalmic Experience: Unanticipated Primary Findings in the Era of Next Generation Sequencing

Factors Which Impact the Delivery of Genetic Risk Assessment Services Focused on Inherited Cancer Genomics: Expanding the Role and Reach of Certified Genetics Professionals