Linking population-based registries to identify familial cancer risk in childhood cancer

Linked population-based registries provide a unique source for identification of new family cancer syndromes and for elucidating risk of early-onset cancer in close relatives of cancer patients.

Using the Finnish Cancer Registry, we identified 9078 probands who had been diagnosed with cancer at <21 years of age between 1970 and 2012. Siblings, offspring, parents, nephews, and nieces of probands were identified from the Population Registry. Childhood and young adult (ChYA) cancer diagnoses (age 0-39 years) in relatives were identified by linking to the Finnish Cancer Registry. The relative risk of ChYA cancer in family members of probands was estimated using standardized incidence ratios (SIRs).

Among 58,010 family members of the 9078 probands, 363 ChYA cancers were diagnosed, 324 of which were expected (SIR, 1.12; 95% CI, 1.01-1.24). The risk of ChYA cancer was elevated both in offspring (SIR, 2.25; 95% CI, 1.51-3.24) and in siblings (SIR, 1.17; 95% CI, 1.01-1.36). Offspring of probands with retinoblastoma were at highest risk (SIR, 75.85; 95% CI, 32.75-149.45); risks were also elevated for siblings of probands with lymphoma (SIR, 1.62; 95% CI, 1.14-2.25). Known cancer predisposition syndromes were observed in 29 (66%) of 44 sibling pairs with cancers diagnosed at <21 years of age and in 20% of the 135 families with a childhood cancer proband whose sibling was diagnosed with a young adult malignancy.

Linked population-based registry data indicate a modestly increased risk of ChYA in relatives of children with cancer. Some of the observed cancer clusters in the cohort suggest novel patterns and familial cancer syndromes.