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Grant Details

Grant Number: 5R00CA256216-04 Interpret this number
Primary Investigator: Makhnoon, Sukh
Organization: Ut Southwestern Medical Center
Project Title: Multilevel Investigation of Uncertain and Reclassified Genomic Variants in Clinical Oncology
Fiscal Year: 2023


PROJECT SUMMARY/ABSTRACT The overarching goal of this award is to prepare the applicant for an independent, sustained program of research that incorporates psychosocial, behavioral, and clinical concepts and methods to understand and design interventions to guide clinical translation of uncertain and reclassified genomic variants. Variants of uncertain significance (VUS) introduce uncertainty and can confuse clinical decision making for patients and providers. VUS are also frequently reclassified, especially in racial/ethnic minority populations, and can inform clinical decision making. However, insufficient evidence around the influences and outcomes of uncertain and reclassified variants presents a challenge for more diffuse clinical translation of these genetic variants. Such understanding is particularly important in clinical oncology, as identification of mutation carriers can significantly alter cancer prevention, screening, surgery recommendations, and treatment. The K99 phase is designed to augment the candidate's prior research experience though coursework, apprenticeships and directed readings with specific training in: 1) clinical health informatics, 2) psychometrics and survey methodology, and, 3) advanced qualitative methods. The proposed research will collect patient reported and electronic medical record data from six healthcare systems that provide clinical genetic services to a racially/ethnically diverse patient population. Aim 1 (K99 phase) surveys a national sample of oncology providers to understand their practices related to variant reclassification and recontact. Aim 2 (K99 phase) interviews patients to identify dimensions of reclassification associated psychosocial well-being. Aim 3 (R00 phase) uses data from aim 2 and existing literature to develop and pilot an instrument to measure genomic uncertainty in patients. Aim 4 (R00 phase) evaluates the clinical utility of variant reclassification. This work will generate evidence to inform institutional and professional practice around variant reclassification. Taken together, the findings from this study will contextualize, and provide tools for a future longitudinal study to determine the behavioral, psychosocial, and clinical consequences of receiving uncertain genetic test results. This project is a critical building block for the applicant's long-term research goal to develop and test interventions (at the levels of provider, patient and healthcare system) to facilitate the clinical translation of genomics into diverse health systems and into underserved populations. The proposed award will provide training, mentorship and research experience that will serve as the foundation for the applicant's career as an independently funded clinical investigator dedicating to improving health outcomes in translational genomics for underrepresented minority populations.


What do cancer genetic providers want us to know about variant reclassification and recontact that we are not asking? A thematic analysis of open-ended survey responses.
Authors: Brown K. , Ponton M. , Davidson E. , Arun B. , Volk R.J. , Shete S. , Peterson S.K. , Makhnoon S. .
Source: Cancer, 2024-06-06; , .
EPub date: 2024-06-06.
PMID: 38843377
Related Citations

Practices and Views of US Oncologists and Genetic Counselors Regarding Patient Recontact After Variant Reclassification: Results of a Nationwide Survey.
Authors: Makhnoon S. , Davidson E. , Shirts B. , Arun B. , Shete S. .
Source: JCO precision oncology, 2023 Jun; 7, p. e2300079.
PMID: 37384863
Related Citations

A multicenter study of clinical impact of variant of uncertain significance reclassification in breast, ovarian and colorectal cancer susceptibility genes.
Authors: Makhnoon S. , Levin B. , Ensinger M. , Mattie K. , Volk R.J. , Zhao Z. , Mendoza T. , Shete S. , Samiian L. , Grana G. , et al. .
Source: Cancer medicine, 2023 Feb; 12(3), p. 2875-2884.
EPub date: 2022-11-24.
PMID: 36426404
Related Citations

Clinical Cancer and Direct-to-Consumer Genetic Test Result-Sharing Behavior: Findings from HINTS 2020.
Authors: Makhnoon S. , Yu R. , Peterson S.K. , Shete S. .
Source: Journal of personalized medicine, 2022-12-22; 13(1), .
EPub date: 2022-12-22.
PMID: 36675679
Related Citations

Use of breast surveillance between women with pathogenic variants and variants of uncertain significance in breast cancer susceptibility genes.
Authors: Makhnoon S. , Chen M. , Levin B. , Ensinger M. , Mattie K.D. , Grana G. , Shete S. , Arun B.K. , Peterson S.K. .
Source: Cancer, 2022 Oct; 128(20), p. 3709-3717.
EPub date: 2022-08-23.
PMID: 35996941
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Patients with cancer have a higher suicide risk: Two new reports conclude that people with cancer are at higher risk for suicide and self-harm: Two new reports conclude that people with cancer are at higher risk for suicide and self-harm.
Authors: O'Rourke K. .
Source: Cancer, 2022-09-15; 128(18), p. 3275-3276.
PMID: 36018006
Related Citations

Are beliefs about the importance of genetics for cancer prevention and early detection associated with high risk cancer genetic testing in the U.S. Population?
Authors: Makhnoon S. , Maki K.G. , Yu R. , Peterson S.K. , Shete S. .
Source: Preventive medicine reports, 2022 Jun; 27, p. 101781.
EPub date: 2022-03-29.
PMID: 35378849
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Helping Patients Understand and Cope with BRCA Mutations.
Authors: Makhnoon S. , Arun B. , Bedrosian I. .
Source: Current oncology reports, 2022 Jun; 24(6), p. 733-740.
EPub date: 2022-03-18.
PMID: 35303253
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Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation of Acceptability and Usability.
Authors: Sheshadri A. , Makhnoon S. , Alousi A.M. , Bashoura L. , Andrade R. , Miller C.J. , Stolar K.R. , Arain M.H. , Noor L. , Balagani A. , et al. .
Source: JMIR formative research, 2022-02-07; 6(2), p. e29393.
EPub date: 2022-02-07.
PMID: 35129455
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Increasing referral of at-risk women for genetic counseling and BRCA testing using a screening tool in a community breast imaging center.
Authors: Arun B.K. , Peterson S.K. , Sweeney L.E. , Bluebond R.D. , Tidwell R.S.S. , Makhnoon S. , Kushwaha A.C. .
Source: Cancer, 2022-01-01; 128(1), p. 94-102.
EPub date: 2021-08-23.
PMID: 34424535
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Uptake of cancer risk management strategies among women who undergo cascade genetic testing for breast cancer susceptibility genes.
Authors: Makhnoon S. , Tran G. , Levin B. , Mattie K.D. , Dreyer B. , Volk R.J. , Grana G. , Arun B.K. , Peterson S.K. .
Source: Cancer, 2021-10-01; 127(19), p. 3605-3613.
EPub date: 2021-06-22.
PMID: 34157779
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Clinical management among individuals with variant of uncertain significance in hereditary cancer: A systematic review and meta-analysis.
Authors: Makhnoon S. , Bednar E.M. , Krause K.J. , Peterson S.K. , Lopez-Olivo M.A. .
Source: Clinical genetics, 2021 Aug; 100(2), p. 119-131.
EPub date: 2021-04-21.
PMID: 33843052
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Factors Influencing Discussion of Cancer Genetic Testing with Health-Care Providers in a Population-Based Survey.
Authors: Makhnoon S. , Yu R. , Cunningham S.A. , Peterson S.K. , Shete S. .
Source: Public health genomics, 2021; 24(3-4), p. 160-170.
EPub date: 2021-04-22.
PMID: 33887738
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