In Case You Missed It: Cancer Risk in Children With Birth Defects

Abstract

In a study published in June 2012, Carrozza et al reviewed data from Texas registries on cancer and birth defects to assess whether specific birth defects increase the risk of childhood cancer.1 Within the cohort of 3 million children born over a 10-year period, these investigators identified 115,686 children with birth defects and 2,351 cases of cancer. Children with an identified birth defect had a threefold increased risk of developing cancer (incidence rate ratio [IRR] = 3.05; 95% CI, 2.65-3.50). This increased risk was most pronounced in the following subgroups: germ cell tumors (IRR = 5.19), retinoblastomas (IRR = 2.34), soft-tissue sarcomas (IRR = 2.12), and leukemias (IRR = 1.39). With the exception of musculoskeletal birth defects, all birth defect groups had increased cancer incidence. The strongest association was seen in children with chromosomal defects (IRR = 15.52), due to the high incidence of leukemia among Down syndrome children (51 of 55 trisomy cancer cases were children with trisomy 21 and leukemia).Previous studies have demonstrated an increased risk of developing cancer for children with identified birth defects.24 This study provides additional convincing data to support that association, and new data about risk stratification based on type of birth defect. The large size of the study cohorts made a revealing subgroup analysis feasible. The data analysis convincingly demonstrates that in this cohort, children with birth defects were at increased risk for cancer development compared to those without birth defects.The strong association between trisomy 21 and leukemia has been cited as responsible for much of the increased risk of cancer in children with birth defects.5 Although the data are not presented in the article, the authors report that they also analyzed the study cohort after excluding any child with a chromosomal anomaly. This resulted in a lower incidence rate for both leukemias and total cancers, but unchanged or increased risk for all other cancer categories. This information greatly strengthens support for the association between nonchromosomal birth defects and cancer risk.The authors acknowledge several weaknesses of the study, including the lack of death certificate linkage, which prevented adjustment for person-year contributions for children who died before the end of the study. The maximum follow-up time was 10 years, resulting in a likely underrepresentation of cancers that occur more commonly or exclusively in late childhood or beyond. In addition, minor structural birth defects may go undiagnosed in otherwise healthy children, but are more likely to be diagnosed in children with serious underlying illness, leading to a potential bias. Finally, the study was not designed to stratify infants with isolated versus multiple defects, and the authors point out that correlation of multiple birth defects and cancer risk could be informative.Although it was not within the scope of this study to determine a causal relationship between birth defects and cancer, the authors speculate about several possibilities that might explain the observed association. They postulate that birth defects may confer genetic susceptibility to environmental exposures, or that the developmental genes responsible for body plan formation during embryogenesis may be linked to cancer development.6 Well-designed, comprehensive studies such as this one can provide insights into these important connections between birth defects and childhood cancer.