Psychological Impact of Multi-Gene Panel Testing in Cascade Programs

Multi-gene panel testing (MGPT) has emerged as a significant tool in cascade testing for hereditary cancers, allowing for the identification of genetic variants of uncertain significance (VUS) or pathogenic variants (GPVs) not detected in the proband. This study is the first prospective evaluation of the psychological impact of MGPT on unaffected relatives of individuals with hereditary cancer. Traditionally, cascade testing has relied on single-site assays, but MGPT offers a more comprehensive approach by screening inherited risks from both maternal and paternal lineages.

Nature

The study found that the overall psychological distress among unaffected relatives was low, with only 6.5% classified as experiencing high distress. Factors contributing to this low level of distress included the participants' awareness of their 50% carrier probability, their decision to receive comprehensive MGPT results, and the provision of genetic counseling, which was received by 98% of participants. However, a subset of GPV carriers did report increased distress after result disclosure, highlighting the necessity for individualized psychological support.

Nature

The psychological impact varied significantly among family members. Children of the proband exhibited higher distress levels compared to siblings or parents, suggesting that familial relationships play a crucial role in emotional responses to genetic testing. Additionally, participants whose probands had pancreatic cancer reported higher cancer worry, likely due to the poor prognosis associated with this disease. This study is notable for comparing the psychological effects of different cancer types, including pancreatic cancer, on unaffected relatives.

Nature

Cultural background also influenced psychological responses. In Asian contexts, hereditary diseases are often stigmatized, which may exacerbate distress during family discussions about cancer risk. Interestingly, while frequent family discussions were associated with higher distress in some cases, more than half of those engaging in such conversations reported low distress but high cancer worry. This complex relationship suggests that detailed family communication may enhance awareness of personal and familial cancer risks.

Nature

The findings indicate that psychological responses to MGPT are influenced by pre-existing cancer worry, necessitating continuous psychological assessment from the pre-test phase. Tailored psychological support should consider the age of individuals and their familial relationship with the proband. The study also emphasizes the importance of targeted educational interventions to motivate screening behavior among unaffected relatives carrying GPVs.

Nature

The study acknowledges several limitations, including potential selection bias due to participant self-selection and the limited prevalence of additional GPVs among probands. The psychological responses observed may not fully represent those in routine clinical practice, as participants were part of a research framework. Further research with larger sample sizes is warranted to explore the psychological impacts of MGPT comprehensively.

Nature

• “This suggests that psychological responses are influenced by preexisting cancer worry, highlighting the importance of continuous psychological assessment from the pre-test phase to inform individualized support strategies.” — Study Author

Nature

• “Our results suggest that familial relationships are important factors in evaluating post-disclosure distress.” — Study Author

Nature

• “Our findings suggest that cultural background, coupled with heightened emotional sensitivity or negative expressions during family conversations, may trigger distress.” — Study Author

Nature

• “Targeted educational interventions that emphasize the importance of surveillance are warranted for unaffected relatives carrying GPVs.” — Study Author

Nature

This study contributes valuable insights into the psychological implications of MGPT in cascade testing, advocating for personalized support strategies to address the emotional needs of unaffected relatives.

Nature