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Some birth defects may carry an increased cancer risk, according to a recent report, but researchers stop short of recommending routine screening.
Birth defects already lead to a host of health concerns, and now researchers are adding childhood cancers to that list. Overall, their new report estimates the overall prevalence of childhood cancers attributed to birth defects at 9.2%. However, the absolute risk of cancer in children with any birth defect remains at 1%.
Chromosomal abnormalities have long been associated with cancer risk, but there is increasing evidence that nonchromosomal abnormalities also increase cancer risk. This study, published in JAMA Oncology, sought to quantify that risk.
Cancer remains the leading cause of death in individuals aged younger than 20 years in the United States, according to the report, and more than 250,000 children are diagnosed with cancer globally each year. Being born with birth defects is one of the strongest known risk factors for childhood cancer, according to the researchers.
The multistate study used data on more than 10 million children born in Texas, Arkansas, Michigan, and North Carolina between 1992 and 2013. The children were followed for 18 years to track cancer diagnoses. Of the sample size, researchers found that nearly 540,000 children were born with a birth defect, and about 15,000 of them were later diagnosed with a cancer. Results were similar across racial subgroups, the report notes.
Birth defects increase likelihood of cancer
The study showed that compared with children who were born with no birth defects, children with chromosomal abnormalities were 11.6 times more likely to be diagnosed with cancer, and children with nonchromosomal birth defects were 2.5 times more likely to be diagnosed with cancer before age 18 years. Researchers also found that children who had more than one nonchromosomal birth defect had corresponding increases in cancer risk as the number of defects rose. For example, children with 4 or more birth defects were 5.9 times more likely to be diagnosed with cancer compared with those without a birth defect, according to the report.
“We reported increased risks for several childhood cancers-notably germ cells tumors and embryonal tumors like hepatoblastoma and neuroblastoma-among children with nonchromosomal structural birth defects,” says Jeremy Schraw, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, Texas, and co-author of the report. “We also reported that cancer risk during childhood increased in proportion to the number of birth defects a child had been diagnosed with. This was true for all cancers combined, as well as for hematologic malignancies, central nervous system tumors, and non–central nervous system solid tumors.”
Schraw says childhood cancers are rare and the absolute risk of cancer for children aged to 18 years was low-less than 1% in almost all circumstances-limiting the immediate clinical implications of the study. Still, Schraw says he hopes the study will lead to additional research and, ultimately, fewer childhood cancers, earlier detection, and improved prognosis.
The goal of the study, Schraw says, was to describe specific birth defect-childhood cancer associations.
“Understanding which birth defects are associated with increased cancer risk is an important first step toward prevention and detection,” Schraw says. “Because the absolute risk of childhood cancer was low even for children with birth defects, we do not presently believe that screening is warranted.”
Birth defects and cancer types
The study did uncover varying risk by specific cancer types and groups of birth defects, and made several observations. For example, bone tumors were not associated with any birth defects, and germ cell tumors were associated with defects in multiple organ systems. There were also 5 specific associations between chromosomal abnormalities or single-gene disorders and childhood cancers-hepatoblastoma in children with trisomy 18; acute myeloid leukemia in children with trisomy 21; and astrocytoma and nonrhabdomyosarcoma soft-tissue sarcoma in children with neurofibromatosis. Additionally, hydrocephaly was associated with 2 central nervous system tumors-astrocytoma and ependymoma, according to the report. The highest cancer risks in children with nonchromosomal birth defects were noted in children with biliary atresia and spina bifida, according to the report.
As far as what types of birth defects were most commonly associated with cancer risks overall, Schraw says there were associations with several types of congenital heart disease and childhood cancer, especially embryonal tumors. “We also found associations between several central nervous system or craniofacial defects and childhood cancers, particularly central nervous system tumors,” Schraw says.
Although the study did not yield a screening recommendation, Schraw says he hopes it will lead to additional research and breakthroughs in cancer surveillance and treatment.
“We hope that by characterizing specific birth defect-cancer associations, we will inform future research into genetic and environmental risk factors for these cancers,” Schraw says. “We anticipate that these future studies will identify genetic variants that play a role in the development of childhood cancers and that may have utility for screening, and environmental risk factors for the co-occurrence of birth defects and childhood cancer, which may be targets for future prevention efforts.”