Around 10% of children with cancer carry a germline pathogenic or likely pathogenic variant (P/LPV) in one of the cancer predisposition genes. The objective of this study was to evaluate the frequency of genetic testing for hereditary cancer predisposition syndromes (HCPSs) among adults treated for childhood cancer in Slovenia and to characterize the P/LPVs identified in those who opted for genetic testing. We also aimed to analyse how a positive genetic test influences cascade testing in blood relatives.

We included patients born between 1970 and 2000 who were diagnosed and treated for cancer between ages 0 − 18 into this retrospective, descriptive, cross-sectional study. Data were collected from the Cancer Registry of the Republic of Slovenia, Long-term Follow-Up Clinic (LTFUC) and the Department of Clinical Cancer Genetics (DCCG) databases. The proportion of tested individuals was calculated with a 95% confidence interval (CI) using the Wald’s method.

Of 1,475patients diagnosed and treated for cancer in childhood, 59 (4.0%; 95% CI: 3.0–5.0%) underwent genetic testing, with 35.6% (21/59) testing positive. The P/LPV were most frequently found in RB1, NF1, RET and BRCA2 genes. In 61.9% (13/21) of positive cases, an identified cancer predisposition syndrome was linked to the childhood cancer; in 95.2% (20/21) it conferred an increased adult cancer risk. Among six patients with P/LPV and second primary cancer (SPC), two had SPC with possible association with the HCPS. Cascade genetic testing was performed in 38.1% (8/21) of positive families and was documented for 35 relatives of 8 carriers of P/LPV. Overall, 60% (21/35) of relatives were positive at genetic testing and 47.6% (10/21) of developed cancer. In 90% (9/10) of relatives the cancer could be linked to the HCPS.

Only 4% of childhood cancer survivors underwent genetic testing for HCPS. Since hereditary cancer predisposition identified in childhood may also increase cancer risk in adulthood, universal cancer genetic counselling and testing should be considered in childhood to timely enable preventive options for early cancer detection and risk reduction procedures in carriers of P/LPV. In parallel, cascade genetic testing among blood relatives may also offer preventive opportunities to those at risk.