Multilevel investigation of uncertain and reclassified genomic variants in clinical oncology

临床肿瘤学中不确定和重新分类的基因组变异的多层次研究

• 批准号: 10353403
• 负责人: Sukh Makhnoon
• 金额: $ 10.78万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2022-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10353403
• 关键词: Affect; Anxiety; Award; Behavioral; Cancer Patient; Classification; Clinical; Clinical Investigator; Clinical Oncology; Communication; Comprehensive Cancer Center; Computerized Medical Record; DNA Sequence Alteration; Data; Decision Making; Development; Diffuse; Dimensions; Early Diagnosis; Early treatment; Ensure; Foundations; Frequencies; Fright; Funding; Future; Genetic Services; Genomic medicine; Genomics; Goals; Guidelines; Health; Health system; Healthcare Systems; Human; Individual; Institutional Practice; Intervention; Interview; Investigation; Knowledge; Length; Literature; Longitudinal Studies; Malignant Neoplasms; Measures; Medical; Medical Genetics; Mentorship; Methods; Minority Groups; Oncology; Operative Surgical Procedures; Outcome; Patient Care; Patient Outcomes Assessments; Patients; Perception; Phase; Practice Guidelines; Prevalence; Professional Practice; Program Sustainability; Provider; Psychometrics; Public Health Informatics; Qualitative Methods; Reading; Recommendation; Recontacts; Reporting; Research; Risk; Sampling; Site; Source; Structure; Subgroup; Surgical Management; Survey Methodology; Surveys; Test Result; Testing; Time; Training; Uncertainty; Underrepresented Minority; Underserved Population; United States; Update; Ursidae Family; Validation; Variant; Work; apprenticeship; cancer prevention; career; clinical decision-making; clinical translation; clinically relevant; clinically significant; cohort; cost; design; ethnic diversity; ethnic minority; ethnic minority population; evidence based guidelines; experience; genetic technology; genetic testing; genetic variant; genome sequencing; improved; instrument; mutation carrier; novel; patient population; psychosocial; psychosocial wellbeing; racial and ethnic; racial minority population; screening; sociodemographics; therapy design; tool; translational genomics; variant of unknown significance

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.

项目总结/文摘

项目成果

Helping Patients Understand and Cope with BRCA Mutations.

• DOI: 10.1007/s11912-022-01254-8
• 发表时间: 2022-06
• 期刊: Current oncology reports
• 影响因子: 4.7
• 作者: Makhnoon S;Arun B;Bedrosian I
• 通讯作者: Bedrosian I

Factors Influencing Discussion of Cancer Genetic Testing with Health-Care Providers in a Population-Based Survey.

• DOI: 10.1159/000515465
• 发表时间: 2021
• 期刊: Public health genomics
• 影响因子: 1.7
• 作者: Makhnoon S;Yu R;Cunningham SA;Peterson SK;Shete S
• 通讯作者: Shete S

Clinical management among individuals with variant of uncertain significance in hereditary cancer: A systematic review and meta-analysis.

• DOI: 10.1111/cge.13966
• 发表时间: 2021-08
• 期刊: Clinical genetics
• 影响因子: 3.5
• 作者: Makhnoon S;Bednar EM;Krause KJ;Peterson SK;Lopez-Olivo MA
• 通讯作者: Lopez-Olivo MA

Clinical Cancer and Direct-to-Consumer Genetic Test Result-Sharing Behavior: Findings from HINTS 2020.

• DOI: 10.3390/jpm13010018
• 发表时间: 2022-12-22
• 期刊: JOURNAL OF PERSONALIZED MEDICINE
• 作者: Makhnoon, Sukh;Yu, Robert;Peterson, Susan K.;Shete, Sanjay
• 通讯作者: Shete, Sanjay

Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation of Acceptability and Usability.

• DOI: 10.2196/29393
• 发表时间: 2022-02-07
• 期刊: JMIR formative research
• 影响因子: 2.2
• 作者: Sheshadri A;Makhnoon S;Alousi AM;Bashoura L;Andrade R;Miller CJ;Stolar KR;Arain MH;Noor L;Balagani A;Jain A;Blanco D;Ortiz A;Taylor MS;Stenzler A;Mehta R;Popat UR;Hosing C;Ost DE;Champlin RE;Dickey BF;Peterson SK
• 通讯作者: Peterson SK