Increased cancer risk in families with pediatric cancer is associated with gender, age, diagnosis, and degree of relation to the child

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BACKGROUND: Studies of cancer risk among relatives of children with cancer beyond parents and siblings are limited. We have investigated the cancer risk up to the third degree of relation in families with pediatric cancer to reveal patterns of inheritance.

METHODS: A single-center cohort of 757 pediatric cancer patients was linked to the Swedish National Population Register, resulting in 16 137 relatives up to the third degree of relation. All relatives were matched to the Swedish Cancer Register and standard incidence ratios (SIRs) were calculated to define relatives at risk.

RESULTS: Children and adults up to the third degree of relation had increased cancer risk, with SIRs of 1.48 (P=0.01) and 1.07 (P<0.01), respectively. The SIRs for first- and third-degree adult relatives were 1.22 and 1.10, respectively, but no increased risk was observed in second-degree relatives. Male relatives had a higher risk than females, especially when related to a girl and when the child had leukemia. The risk was mainly increased for lung, prostate and gastrointestinal cancer. When excluding 29 families of children with known pathogenic germline variants, the increased risk remained.

CONCLUSION: Relatives to children with cancer up to third degree of relation have an increased cancer risk. Known pathogenic germline variants do not explain this increased risk.

IMPACT: The overall increased cancer risk among relatives of children with cancer in this population-based cohort strengthens the importance of surveillance programs for families with pediatric cancer.