Cancer in siblings of children with cancer in the Nordic countries: a population-based cohort study

Background In some rare inherited disorders such as Li-Fraumeni syndrome, r elatives of children with cancer are at increased risk of cancer. We aimed to assess relations between childhood cancer and sibling risk, and evaluate the influence of recessive conditions in cancer causation. Methods We did a population-based cohort study in the Nordic countries of 4 2 277 siblings of 25 605 children with cancer. Children with cancer were id entified from records in the five Nordic cancer registries, and their sibli ngs from nationwide population registries. Cancers in siblings were documen ted through record linkage with cancer registries and compared with nationa l incidence rates. We also assessed cancer incidence in parents to identify familial cancer syndromes. Findings 284.2 cancers were expected in siblings, whereas 353 were diagnose d (standardised incidence ratio 1.24 95% CI 1.12-1.38). Risk ratios for sib lings were highest in the first decade of life (2.59, 1.89-3.46). We exclud ed 56 families with genetic syndromes linked to cancer, which reduced this ratio from 1.7 to 1.0 (0.7-1.3) for siblings younger than 20 years, and fro m 1.3 to 1.0 (0.8-1.3) for those aged 20-29 years. We found no new patterns of familial cancer that indicated inherited susceptibility, or evidence th at recessive conditions might contribute to cancers not explained by syndro mes. 40% of cancers in siblings that occurred before age 20 years could be attributed to known genetic factors, whereas 60% remained unexplained. Interpretation Apart from rare cancer syndromes, paediatric cancer is not a n indicator of increased cancer risk in siblings.