Familial disclosure of mutational status and cascade testing: Relationships with cancer-predisposing genes and race/ethnicity.
Authors: Manirakiza Achille Van Christ , Freeman Jincong Q. , Zhao Fangyuan , Keel Emma Van Christ , Bradley Robin , Drogan Christine , Huo Dezheng , Olopade Olufunmilayo I. 
Published: June 2024

10605

Background: Patients (pts) with cancer-predisposing genes may differ in the patterns of genetic testing disclosure to family members and cascade testing. We examined the relationships between varying levels of cancer-predisposing gene penetrance and racial/ethnic differences in familial disclosure and cascade testing. Methods: Between July-September 2023, we conducted a follow-up survey of pts enrolled in the University of Chicago Cancer Prone Study, a longitudinal cohort of high-risk families initiated in 1992. Pts were asked questions about familial disclosure and cascade testing, including whether they 1) carry a gene mutation(s); 2) told any family member about their mutation status; 3) received a family letter from their genetic counselors after testing; and 4) had any family member having undergone testing for the familial mutation(s). Chi-squared or Fisher’s exact tests were performed. Results: Of 912 respondents, 35.3% (n=312) reported carrying a genetic mutation. The mean age was 54.8 years (SD=13.7); 86.9% were White, followed by 4.8% Black, 5.1% Hispanic, and 3.2% other/multiracial; 45.8% had a graduate/professional degree; 31.5% had an annual household income of ≥$200,000; 70.9% and 23.9% were privately insured and on Medicare/Medicaid, respectively. Among pts with a genetic mutation, 37.8% had a BRCA1 (n=63) or BRCA2 (n=55) mutation. The vast majority (96.5%) disclosed their mutation status to a family member. The disclosure status differed significantly by race/ethnicity (Hispanic 100.0%, White 98.5%, Black 92.3%, vs. other/multiracial 80.0%; p=0.013). First-degree relatives were the most communicated to, and the most cited reasons for disclosure were “awareness of potential risk” (n=264) and “support preventive measures” (n=224). Among pts carrying a gene mutation, 50.6% (n=158) reported having received a letter from their genetic counselors to share with any family member and of these, 82.2% (n=129) did share their family letters. Among pts who did not receive or did not know if they received a letter (n=149), 41.6% stated that the letter would have helped them disclose the information to their family members. Further, 79.1% of the pts reported that their family members underwent genetic testing, with no significant differences in cascade testing by race/ethnicity and other demographic characteristics. However, pts with a positive mutation in BRCA1or BRCA2 (92.6%) were more likely to have a cascade testing, when compared to pts with other mutations (76.8%; p<0.001). Conclusions: Although familial disclosure of mutational status was high, cascade testing was not high enough and it depends on the penetrance of cancer-predisposing genes. Understanding genetic testing disclosure and cascade testing from a gene-to-gene basis could help improve genetic counseling and risk communication particularly for racial/ethnic minority pts.