- Recently published in the Journal of Medical Genetics* results of a case-control study spearheaded by VHIO’s Judith Balmaña show that secondary findings from exome sequencing uncover mutations in cancer susceptibility genes in patients with rare, non-oncological diseases without a personal or family history of cancer.
- In their retrospective analysis of exome sequencing data of 533 patients, the investigators studied the frequency of secondary and incidental findings in cancer susceptibility genes, their clinical actionability and the psychological impact of these results in patients and their families.
- At least one cancer-related secondary/incidental finding was identified in 2.1% of these patients. These findings led to 20 individuals enrolling in a cancer surveillance program, 20% of whom were subsequently diagnosed with cancer, the majority presenting with early-stage disease.
- While secondary findings can be of utility in the early detection of cancer in some of patients, the psychological impact of impact is significantly higher in these individuals compared to patients who are routinely tested due to a personal or family history of cancer.
- Results of this present study illuminate the need for strengthening tailored genetic counselling to help patients cope with secondary findings and justify further research into new genetic delivery models and frameworks to lessen the psychological burden.
Recently published in the Journal of Medical Genetics*, results of case-control retrospective study led by Judith Balmaña, Principal Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Hereditary Cancer Genetics Group, in collaboration with researchers at the Vall d’Hebron Research Institute (VHIR), report on the clinical and psychological implications of secondary and incidental findings (SF/IF) in cancer susceptibility genes after exome sequencing in patients with rare, non-oncological disorders without a personal or family history of cancer.
Exome sequencing is a genomic technique currently being used in patients with suspected rare genetic diseases. In individuals with a clinical history of developmental delay or intellectual disability, it has become a first-tier test for routine diagnostics and is also used as a first-line diagnostic procedure in the clinic for disorders with an uncertain phenotype.
“Secondary and incidental findings in exome sequencing, however, are unrelated to the initial indication for exome sequencing. One of the main concerns regarding the impact of returning results of unexpected variants to patients, such as mutations identified in cancer susceptibility genes, is the psychological impact of these unexpected results in patients and their families,” says Judith Balmaña, senior author of this present study.
In the medical genetics community, a hotly debated issue surrounds the disclosure of these unintended data to the patient and/or family with several different policy statements for managing SF/IFs elaborated and published by international scientific societies.
Carried out in collaboration with colleagues of the Vall d’Hebron Research Institute’s (VHIR) Clinical and Molecular Genetics, Pediatric Oncology and Hematology, and Neuropediatric Groups, this case-control retrospective study was designed to assess the frequency of SF/IF in cancer susceptibility genes and establish the clinical actionability of these results as well as the psychological impact in patients with incidental results versus those patients with a personal or family history of cancer who underwent standard cancer genetics risk assessment and counselling.
The investigators analyzed exome sequencing results from 533 patients who were tested for non-oncological pathologies at the Vall d’Hebron University Hospital’s (HUVH) Department of Clinical and Molecular Genetics from 01 January 2018 to 30 September 2020, which yielded a 2.1% cancer-related SF/IF, the most frequent of which were BRCA1/2 gene variants.
“We measured the psychological impact of these secondary and incidental findings in these individuals, who were mainly pediatric patients, compared to that observed in the cohort of patients receiving similar genetic results within a family history of cancer. While we observed a significantly higher psychological impact in those patients without a family history of cancer, the clinical actionability of these findings is important,” adds Estela Carrasco, first author of this present study, a Genetic Counsellor and Predoctoral Investigator of Judith Balmaña’s group.
Twenty patients with identified cancer susceptibility genes and their family members were included in tailored cancer surveillance, which subsequently prompted a cancer diagnosis in 20% of these individuals. Most of these patients presented with early-stage disease and received treatment. 80% of these relatives had no familial history of cancer.
Findings also show a 92% rate of acceptance for receipt of secondary results with only 8% of the participants choosing to opt out for this type of disclosure, underpinning the importance of developing adequate delivery models of SF/IF disclosure to ensure that results translate into valuable actions for patients and their family members.
“Our results illuminate the need for multidisciplinary teams, including experts in genetic counselling, clinical geneticists and medical oncologists specialized in hereditary cancer, to help patients and family members to cope with secondary and incidental findings. This study also supports further research into new genetic delivery models to lessen the psychological impact of these unexpected, secondary results,” concludes study lead Judith Balmaña.
*Carrasco E, López-Fernández A, Codina-Sola M, Valenzuela I, Cueto-González AM, Villacampa G, Navarro V, Torres-Esquius S, Palau D, Cruellas M, Torres M, Perez-Dueñas B, Abulí A, Diez O, Sábado-Álvarez C, García-Arumí E, Tizzano EF, Moreno L, Balmaña J. Clinical and psychological implications of secondary and incidental findings in cancer susceptibility genes after exome sequencing in patients with rare disorders. J Med Genet. 2022 Nov 29:jmg-2022-108929. doi: 10.1136/jmg-2022-108929. Epub ahead of print. PMID: 36446584