Risk of childhood and adolescent, and young adult cancer in offspring of men with testicular cancer: A Danish nationwide study

Data on cancer risk in offspring of men with testicular germ cell cancer (TC) remain limited. We assessed the risk of childhood and adolescent and young adult (AYA) cancer in offspring of men with TC. Men diagnosed with TC in the Danish Cancer Registry (1943-2017) were identified (TC probands). For each TC proband, 10 men matched on birth year, alive, and cancer-free at the proband's date of diagnosis were selected from the National Civil Registration System (non-TC probands). Offspring were identified in the Danish Birth Registry, with cancer diagnoses obtained from national registries. Cumulative incidences, hazard ratios (HRs), with 95% confidence intervals (CIs) were calculated for childhood cancer (0-14 years) and AYA cancer (15-39 years), including TC specifically versus other cancers. Offspring were included regardless of whether they were born before or after their father's diagnosis (for TC probands) or the corresponding index date (for non-TC probands). Childhood cancer rates were similar between sons of TC probands and non-TC probands (HR 1.0, 95% CI 0.6-1.7) and daughters (HR 1.1, 95% CI 0.6-1.9). For AYA cancer, rates in daughters were comparable, while sons of TC probands had an increased rate (HR 1.9, 95% CI 1.6-2.4). This increase was driven by TC (HR 3.6, 95% CI 2.7-4.8), with no significant difference in rates of other cancers. The rate of childhood cancer in offspring of men with TC is comparable to the rate of the general population, while the elevated AYA cancer rate in sons is attributable to a higher rate of TC.