Integrating Medical Genetics Into Precision Oncology Practice in the Veterans Health Administration: The Time Is Now

Abstract

PURPOSE: Increased access and utilization of tumor profiling of cancers in our veteran population uncovered a modest number of potentially pathogenic germline variants (PPGVs) that require genetics referral for follow-up evaluation and germline sequencing. Challenges identified specific to the veteran population include paucity of genetics providers, either at a veteran's VA facility or nearby non-VA facilities. We sought to investigate the number of veterans who would benefit from having such resources at both local and national levels. METHODS: Annotated clinical reports of mutations identified by tumor-only profiling and medical records of veterans with solid tumors at the Veterans Administration Ann Arbor Healthcare System (VA AAHS) between 2015 and 2020 were reviewed. PPGVs were identified according to society recommendations (such as ESMO and American Board of Medical Genetics and Genomics), expert review, and/or previously published criteria. After the analysis of our local VA population, these same criteria were then applied to veterans in the National Precision Oncology Program (NPOP). RESULTS: Two hundred eight veterans underwent tumor profiling at the VA AAHS over the defined time period. This included 20 different primary tumor sites with over half (n = 130) being advanced cancer at diagnosis. Of these, 18 veterans (8.5%) had mutations suggestive of a PPGV. Applying these criteria to the larger NPOP database (n = 20,014), a similar percentage (6%) of PPGVs were identified. CONCLUSION: These results indicate a PPGV frequency (6%-9% of veterans) consistent with the prevalence of inherited cancer predisposition syndromes in the general population, underscoring the need for medical genetics as part of standard oncologic care for veterans. We explore current and future care delivery models to optimize incorporation of medical genetics and genetic counseling to best serve veterans needing such services.

Prevalence of Potentially Pathogenic Germline Variants Among Adult Patients in the Philippines With Solid Malignancies Who Underwent Tumor Genomic Profiling

“…15,16,25 Furthermore, recognition of hereditary risk may also encourage cascade testing of family members. 12,13 In conclusion, incidental potentially germline variants from TGP complements germline evaluation on the basis of hereditary cancer testing guidelines. Given the PPGV prevalence of 11% in this study, we underscore the importance of recognizing PPGVs as it can prompt genetic counseling and appropriate germline testing.…”

“…15,16,25 Furthermore, recognition of hereditary risk may also encourage cascade testing of family members. 12,13…”

“…PPGVs were identified according to society recommendations (European Society for Medical Oncology Precision Medicine Working Group and the American Board of Medical Genetics and Genomics), previously published criteria, and expert review. PPGV criteria include having a VAF of ≥30% and were categorized as (1) high penetrance gene (HP), founder variant (FV), or variant associated with clinical presentation (VA 12 ; Table 1). HPs include any pathogenic variants in genes associated with high-penetrance cancer predisposition syndromes.…”

“…Criteria Used to Identify Potentially Pathogenic Germline Variants9,12,13 CDKN2A in a patient with melanoma, and PTEN in a patient with breast cancer. Four patients (8% of patients with PPGV) had potential germline variants not known to increase the risk of developing their particular tumor type: BRCA2 in a patient with lung cancer, BRCA1 in a patient with leiomyosarcoma, MSH6 in another with prostate cancer, and BRCA2 in a patient with lymphoma (Appendix Table…”