Uptake and associated factors of family-specific variant genetic testing among at-risk relatives of hereditary gynecological cancer probands

Vollständiger Abstract

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Abstract Background Family-specific variant genetic testing is crucial for cancer risk management among at-risk relatives of individuals with hereditary gynecological cancer. However, the uptake of such testing remains suboptimal, and the factors influencing uptake have not been fully elucidated. This study aimed to investigate the uptake of family-specific variant genetic testing among at-risk relatives of probands with hereditary gynecological cancers and to identify factors associated with testing uptake. Methods A cross-sectional study was conducted between August 2023 and September 2024 at the Obstetrics and Gynecology Hospital of Fudan University. Seventy probands with confirmed pathogenic or likely pathogenic (P/LP) germline variants in hereditary gynecological cancer susceptibility genes, along with their 307 at-risk relatives, were enrolled. Self-designed questionnaires were used to collect characteristics of probands and their at-risk relatives, as well as the features of their relationships. Multivariate binary logistic regression analysis was performed to identify factors associated with testing uptake. Results Among the 70 probands, isolated ovarian cancer accounted for the highest proportion of personal malignancies (60.00%), followed by isolated breast cancer (31.43%), while synchronous ovarian and breast cancer was observed in 1.43% of probands. BRCA1/2 g ermline mutations were detected in 90.00% of probands. Among the 307 at-risk relatives, the overall uptake rate of family-specific variant genetic testing was 36.16% (111/307), and 47.75% (53/111) of those tested harbored P/LP germline variants. First-degree relatives comprised 79.48% (244/307) of the relative cohort, with a testing rate of 32.38% (79/244) and a P/LP variant positivity rate of 49.37% (39/79). Multivariable logistic regression revealed that bachelor’s degree or above (OR = 2.106, 95% CI: 1.211–3.664, P = 0.008), very good overall family relationship (OR = 1.905, 95% CI: 1.087–3.340, P = 0.024), and communication frequency ≥ 5 times per month (OR = 3.952, 95% CI: 1.720–9.077, P = 0.001) were independent positive predictors of genetic testing uptake among all at-risk relatives, with similar independent effects observed in the first-degree relative subgroup. Conclusion Uptake of family-specific variant genetic testing among at-risk relatives of hereditary gynecological cancer probands remains limited, despite a substantial proportion of positive findings among those tested. Higher educational attainment, favorable family relationship quality, and frequent intrafamilial communication with the proband independently facilitate testing uptake, which provides a valuable basis for optimizing cascade genetic testing strategies in hereditary gynecological cancer families. These findings further highlight the necessity of implementing family-centered communication interventions and targeted educational support to improve genetic testing uptake in this high-risk population.