“I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants

Abstract

Little is known about what uncertainties patients experience after being identified to carry a pathogenic variant in a moderate-risk cancer gene as a result of undergoing multigene panel testing for cancer susceptibility. Data regarding cancer risk estimates and effectiveness of risk management strategies for these variants continues to evolve, which has the potential to evoke uncertainty. Acknowledging uncertainty during pre- and post-test discussions is imperative to helping individuals to adapt to their results. A better understanding of this population’s experience of uncertainty is needed to facilitate such discussions and is the aim of the current study. Semi-structured interviews (30–60 min in length), informed by Han and colleagues’ taxonomy of uncertainty in clinical genomic sequencing, were conducted to assess motivations to pursue genetic testing, areas of perceived uncertainty, and strategies for managing uncertainty among 20 carriers of pathogenic variants in two moderate-risk genes, ATM and CHEK2. We found that participants pursue genetic testing with the expectation that results will clarify cancer risks and approaches to management. Participants experience uncertainties aligning with Han’s taxonomy relating to the ambiguity of specific cancer risk estimates and effectiveness of certain risk management strategies. These uncertainties influenced decisions around the uptake of risk management strategies, which were additionally impacted by clinicians’ uncertainty towards such strategies. Participants employ a variety of uncertainty management approaches to cope with their anxieties. Clinicians may wish to use these findings to facilitate patient adaptation to the implications of multigene panel testing for cancer susceptibility during both pre- and post-test counseling sessions.

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Data availability

Upon request, the raw data supporting the conclusions of this article will be made available by the authors.

Code availability

Coding of interview transcripts was facilitated by Dedoose (Version 8.2.14, 2019).

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Acknowledgements

This study was completed in partial fulfillment of the requirements of the first author’s Master of Science degree in Human Genetics and Genetic Counseling from Stanford University’s School of Medicine. This work has been supported by the Jane Engelberg Memorial Fellowship Student Research Award, provided by the Engelberg Foundation to the National Society of Genetic Counselors, Inc. We wish to thank the participants of this study for providing their time and their thoughtful responses, and Janine Bruce and Sylvia Bereknyei Merrell for their qualitative methods guidance throughout the study.

Funding

This work was supported by the Jane Engelberg Memorial Fellowship Student Research Award, provided by the Engelberg Foundation to the National Society of Genetic Counselors, Inc.

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Authors

Contributions

Authors KGR, MG, AJN, and KEO designed and conceptualized the study and created the interview guide. KGR conducted all interviews. Development of the codebook and the analysis process was performed primarily by KGR and CC, with assistance from MG and KEO. All authors interpreted these results and developed themes. The first draft of the manuscript was written by KGR, and all authors provided critical feedback and approval of several drafts and the final manuscript.

Corresponding author

Correspondence to Kelly E. Ormond.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Stanford University Institutional Review Board (09/18/2019; #51975).

Consent to participate

A waiver of written documentation of informed consent was granted, given the minimal risk of the study. Participants reviewed an information sheet prior to completing the demographic survey and provided verbal consent at the start of the interview.

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Reyes, K.G., Clark, C., Gerhart, M. et al. “I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants. Familial Cancer (2021). https://doi.org/10.1007/s10689-021-00251-3

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Keywords

  • Uncertainty
  • ATM
  • CHEK2
  • Cancer genetics
  • Genetic testing
  • Qualitative research