Increased cancer risk among siblings of individuals with birth defects

Both birth defects and childhood cancer are rare conditions. In 2021, approximately 4% of liveborn children in Norway had a congenital malformation, and in 2022, 210 children and adolescents (0-17 years) got a cancer diagnosis. Despite extensive research over many decades, the causes of both childhood cancer and birth defects are largely unknown. Increased cancer risk among people with birth defects suggests a common underlying cause. A common cause could mean that siblings of individuals with birth defects also have an increased risk of cancer. It has previously been shown that certain birth defects occur more frequently in families, and childhood cancer has been observed more frequently in families with a history of cancer. However, cancer risk among siblings of children with malformations has not previously been well studied. 

Use of national health registers in the Nordic countries

In order to investigate the connection between having siblings with birth defects and cancer risk we conducted a study, linking data from national birth, malformation and cancer registries in four Nordic countries. Results from the study were recently published in the International Journal of Epidemiology. In the study, we compared people having siblings with birth defects with people whose siblings did not have birth defects. In total, we included over 40,000 individuals with cancer and over 400,000 individuals without cancer aged 0 to 46 years from Denmark, Finland, Sweden, and Norway.

Risk of cancer among siblings of individuals with birth defects

We found no increased risk of cancer in the age group 0 to 46 years among siblings of individuals with birth defects when we looked at all cancers combined. However, we saw a 17% increased risk of acute lymphocytic leukemia among those who had siblings with birth defects. In addition, we found that the cancer risk increased with an increasing number of siblings with birth defects. People with two or more siblings with birth defects had a 1.4 times higher cancer risk compared to people with two or more siblings without birth defects.

Increased risk of childhood cancer among siblings of individuals with birth defects

We included around 15,000 childhood cancer cases (ages 0 to 19 years) in our study. We found that those with siblings with a birth defect had a small increase (9%) in the risk of childhood cancer overall. In particular, we saw a 35% increased risk of lymphoma and a 51% increased risk of neuroblastoma among children with siblings with birth defects. In addition, we found that those with siblings with birth defects of the nervous system had a 1.4 times increased risk of cancer. Certain birth defects among the siblings were also associated with an increased risk of specific cancers: nervous system birth defects and lymphoma, urogenital birth defects and germ cell tumors, as well as musculoskeletal birth defects and neuroblastoma.

Increased risk of cancer among adults with siblings with malformations

Among adults (20 years and older), we found an increased risk of brain tumors (1.3 times higher) and kidney cancer (1.9 times higher) among those who had siblings with birth defects compared to those who had siblings without birth defects.

Need for research

Both (epi)genetic and environmental factors have previously been suggested as common underlying causes of both birth defects and cancer. In this study, we found that the cancer risk among those who had siblings with birth defects was lower than the cancer risk among those who had their own birth defect. This may indicate that many associations between birth defects and cancer may be linked to prenatal developmental disorders. Both birth defects and cancer are heterogeneous groups of diseases, and the relation between them is complex and probably involves combinations of embryonic, epi(genetic), and/or environmental risk factors. Further research into the underlying mechanisms is necessary.

The study was funded by the Norwegian Cancer Society and the Faculty of Medicine, University of Bergen. The study is a collaboration between researchers in Denmark, Finland, Norway, Sweden and the USA, and was led from the University of Bergen.

Reference:
Daltveit DS, Klungsøyr K, Engeland A et al. (2023): Cancer risk in the siblings of individuals with major birth defects: a large Nordic population-based case-control study, International Journal of Epidemiology. https://doi.org/10.1093/ije/dyad113