Cascade testing as the missing link in cancer prevention among Lynch syndrome families

This study examined the uptake and timing of cascade testing in families with Lynch syndrome followed at a single Genetics Service in Northern Italy, with the aim of identifying family and individual factors that may influence uptake of testing in at-risk relatives. All living blood relatives aged ≥ 18 years and eligible for the first step of cascade testing were included. Forty-eight families were examined. Most probands were women (77.1%) mainly affected by endometrial (55.3%) or colorectal cancer (42.6%); the branch segregating the pathogenic variant was known/suspected in 51.1% of families. Overall, the cascade testing uptake was 19.5%. At the family level, uptake ranged from 0 in 47.9 to 100% in 4.2% of families. Binary logistic regression confirmed age and degree of kinship as significant predictors; younger rela- tives were more likely to undergo testing (OR = 0.97 per year, p < .001), while testing likelihood declined across kinship degrees (12-month testing: 27.7% first-degree, 10.4% second-degree, 5.7% more distant relatives; Log Rank p < .001) with Odds Ratios of 0.27 for second-degree and 0.07 for third-degree or beyond. Neither sex (p = .487) nor health status (p = .271) were significantly associated with uptake. Kaplan–Meier analysis showed that uptake occurred mostly within the first 12 months after the proband’s result (86.7% of those tested), after which it plateaued. These real-world findings highlight substantial gaps in cascade testing implementation and provide evidence to guide future strategies aimed at increasing uptake and strengthening family communication of genetic risk in the Italian context.