Image: Spoon agency
Research project Identification of inherited patogenic variants in cancer-predisposing genes in a patient opens up the opportunity of predictive testing to genetic relatives at risk. The question is - how is this information safely and efficiently transferred to the relatives at risk?
If a pathogenic variant in a cancer-predisposing gene is found in a patient, their genetic relatives are at risk and need to be informed to enable cancer prevention efforts. Most genetic clinics currently encourage patients to inform their at-risk relatives, but research shows that some relatives remain uninformed and miss out on prevention. We conducted a clinical trial to see if offering healthcare-assisted disclosure increases the number of at-risk relatives seeking genetic counselling compared to standard patient-led disclosure.
We are conducting a multicenter randomized controlled trial at the cancer genetic clinics in Umeå, Gothenburg, and Lund. Patients invited to the study have an inherited cancerpredisposition (pathogenic variants in BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, Familial breast cancer or Familial colorectal cancer). The patients are randomised to the following arms:
Results from the trial will be reported in 2025.
To understand patients' and relatives' perspectives on risk disclosure, we have performed two qualitative Studies Within A Trial (SWATs):
First SWAT (article in EJHG): We analyzed 17 interviews with patients from both control and intervention groups. Despite agreeing to direct letters, patients also disclosed risk to relatives themselves, especially to close family members. The healthcare-assisted letter was primarily used for distant relatives.
Second SWAT (article in EJHG): We interviewed relatives who received direct letters from healthcare within two weeks of contacting a cancer genetic clinic. Relatives had varying levels of prior knowledge about hereditary cancer risk. Most were notified by a family member about the letter, but some were not. Overall, relatives felt that healthcare-mediated disclosure could complement family-mediated disclosure. They expressed a need for accessible healthcare support when receiving such information and found it easier to cope with the news if a family member had informed them beforehand. They believed healthcare should assist in the disclosure process while ensuring relatives' right to be informed. These findings support healthcare-assisted disclosure as a complement to family-mediated disclosure, but it should be integrated into existing genetic counselling practices.
To optimize the design of the RCT and make sure we incorporate the perspective of both patients, relatives and Swedish citizens - a number of explorative studies were conducted during the years leading up the the implementation of the DIRECT-study.
Public opinion study (article in HCCP): This explorative surveyed 977 Swedish citizens about their preferences for receiving information on hereditary colorectal cancer (CRC) risk. Nearly 90% of participants wanted to be informed if they had an increased risk of cancer (moderate lifetime risk of 10% or high at 70%). Women were more keen to be informed than men. Most participants preferred to speak with a healthcare professionals rather than family members, with letters and phone calls being the favored mode of communication. The results suggest strong public support for healthcare-assisted disclosure of hereditary CRC risk to optimize the effekt of targeted prevention efforts.
Focus group study (article in JPM): This study identified two main themes regarding how the Swedish public perceives genetic risk information about hereditary cancer: “Face an important but difficult challenge” and “Expect healthcare to lead but also support disclosure.” Focus groups (n=18) participants described a moral duty to share risk information despite the emotional burden, and expressed discomfort with laypeople handling complex genetic information without professional support. Surprise and frustration was expressed over current family-mediated disclosure practices, which lack systematic follow-up of at-risk relatives. Participants advocated for a shared responsibility between patients and providers, with a more structured, empathetic, and clinically supervised approach including more personalized information and direct access to enable equal access to informed decision-making.
Patient interview study (article in PEC): This qualitative study examined how individuals actually manage the sharing of hereditary cancer risks with family members. Twelve semi-structured interviews explored patients' experiences following competion of genetic counseling. Counselees employed a number of creative strategies to disclose risk, such as making their own information pamphlets or using a relative as an intermediary. Patients highly valued their interactions with genetic healthcare professionals, finding them crucial for support and guidance. Identified gaps in current practices included unclear information about the counseling process and uncertainty about healthcare professionals' roles in disclosure.
