Birth Defects’ Cancer Risk Persists Into Adulthood

Children with major birth defects had an elevated risk of cancer that persisted into adulthood, a large retrospective cohort study showed.

Overall, 3.5% of 62,295 patients with cancer had major birth defects, compared with 2.2% of a matched control group without cancer. Although the difference was small in absolute terms, the patients with cancer had a 74% higher likelihood of also having a major birth defect, reported Dagrun Slettebø Daltveit, of the University of Bergen in Norway, and colleagues.

Their study, online in BMJ, showed that cancer risk declined with increasing age among children with birth defects, but remained significantly higher for adults with specific types of defects.

“Our study showed that birth defects are associated with risk of cancer in adulthood as well as in adolescence and childhood, a finding of clinical importance for healthcare workers responsible for follow-up of people with birth defects,” the authors concluded. “Surveillance for cancer in children with birth defects has been discussed, but thus far the absolute cancer risk has been regarded as too low.”

“Thus, the most important implication of our results is to provide further rationale for additional studies on the molecular mechanisms involved in the developmental disruptions underlying both birth defects and cancer,” the researchers wrote.

The authors of an accompanying editorial said the immediate implications of the study are limited but that the findings should provide impetus for additional research into the relationship between birth defects and cancer.

“The relation between cancers and birth defects is likely to be complex, and this study did not distinguish between genetic, environmental, and iatrogenic explanations for the observed associations,” wrote Logan G. Spector, PhD, of the University of Minnesota Medical School in Minneapolis, and Lazaros Kochilas, MD, of Emory University School of Medicine in Atlanta. “Future cohort studies may be enhanced by alternative approaches exploring cancer associations not by birth defect phenotypes but by known developmental and molecular pathways, such as neural crest abnormalities or defects in Ras signaling pathways.”

The finding of an increased cancer risk into adulthood is novel and “may be informative for people living with birth defects and their clinicians,” Spector and Kochilas acknowledged.

The researchers noted that children with certain major birth defects are known to have an increased risk of cancer, which varies by the type and number of defects. The cancer risk appears to be highest in young children, but few studies have followed up beyond adolescence.

Birth defects and childhood cancers are both relatively rare, posing a challenge to studies examining potential associations. In an attempt to address the numbers issue, the authors performed a nested case-control study, using national health registries from Denmark, Norway, Sweden, and Finland. The objectives were to identify associations between birth defects and cancer, determine the relationship between number of birth defects and cancer risk, and determine whether associations persisted into adulthood.

Data analysis covered birth years from 1967 to 2014 and included 62,295 patients with cancer and 724,542 matched controls. The 1.3% absolute difference in major birth defects between the cancer and control groups represented a statistically significant increase in the odds ratio (OR) for the patients with cancer (99% CI 1.63-1.84).

Cancer risk was significantly increased for patients with chromosomal anomalies (OR 5.53, 99% CI 4.67-6.54) and those with nonchromosomal birth defects (OR 1.54, 99% CI 1.44-1.64).

The OR for cancer increased with the number of birth defects and decreased with age, the investigators reported. The overall relative risk of cancer in association with birth defects was 11.3 in children (99% CI 9.35-13.8) and 1.50 in adults (99% CI 1.01-2.24).

Birth defects associated with an increased risk of cancer in adulthood included:

• Skeletal dysplasia: OR 3.54, 99% CI 1.54-8.15

• Nervous system: OR 1.76, 99% CI 1.16-2.65

• Chromosomal anomalies: OR 1.50, 99% CI 1.01-2.24

• Genitalia: OR 1.43, 99% CI 1.14-1.78

• Congenital heart defects: OR 1.28, 99% CI 1.02-1.59

The analysis revealed multiple statistically significant associations between specific types of birth defects and specific types of cancer, and the defects and types of cancer varied between children and adults.