Cancer patients' experience of receiving variant of uncertain significance results: An Asian perspective.

Due to a lack of ancestry-matched, functional, and segregation data, Asians have a higher rate of receiving a variant of uncertain significance (VUS) result following panel testing. Managing VUS results presents challenges, as it often leads to increased anxiety and distress among cancer patients undergoing genetic testing. This exploratory study aims to investigate the experience of Asian cancer patients upon receiving a VUS result. A qualitative, semi-structured interview study was conducted, involving cancer patients who had received a VUS result through the Cancer Genetics Service of the National Cancer Centre Singapore. Twenty participants were interviewed, and their responses were transcribed and analyzed using thematic analysis to identify key themes. Thematic analysis revealed five major themes: (1) VUS results are interpreted as uncertain outcomes; (2) a VUS result provides relief and prompts positive behavioral adjustments; (3) patients employ fatalism and religion as coping mechanisms to navigate uncertainty; (4) genetic counselors, family, and the community offer reassurance and support; (5) patients value updates on variant classifications for future management. While this novel study provides unique insights into the perspectives of Asian patients who receive VUS results, it also highlights patients' effective management of VUS results and uncertainty, which has implications for improving counseling practices in Asia. Emphasis must be placed on accurate interpretation and clear communication of VUS results to dispel the possibility of misconceptions, misdiagnosis, and mismanagement in cancer care.

Predictive Testing for Tumor Predisposition Syndromes in Pediatric Relatives: An Asian Experience.

Approximately 10% of pediatric cancer patients possess germline pathogenic/likely pathogenic variants (PV/LPV) in known tumor predisposition genes. Predictive testing is the optimal approach to identify asymptomatic at-risk relatives to guide gene-directed surveillance for early cancer detection and/or risk-reducing strategies. However, the uptake rate for predictive testing remains low in Asian countries. We aim to evaluate the uptake rate of predictive testing in a pediatric population (aged under 21-years-old) in a multi-ethnic Asian cancer center. Our retrospective analysis included families with PV/LPVs identified in genes associated with pediatric tumor predisposition. Of the 83 pediatric first-degree relatives (FDRs) from 49 unrelated families, 20 FDRs (24.1%) originating from 13 families (26.6%) underwent predictive testing. Genes tested in pediatric FDRs were APC, RB1, SBDS, SDHA, SDHB, SDHD, and TP53. All pediatric FDRs of probands with PV/LPVs in RB1 and biallelic PVs in SBDS underwent predictive testing, while <45% of pediatric FDRs had predictive testing for familial PV/LPVs identified in the APC, SDHA, SDHB, SDHD, and TP53 genes. Amongst the 13 families who underwent pre-test counseling, 80% of pediatric FDRs in these families proceeded with predictive testing. Malay pediatric FDRs and siblings of probands were more likely to undergo predictive testing. We conclude that the predictive testing rate in pediatric FDRs is higher than that of adult FDRs in Asia, but still below the global average. We postulate factors that may influence predictive testing uptake in pediatric FDRs includes a lack of genetics awareness, concerns regarding insurance, and genetic discrimination.