Birth Defects Raise Risk for Childhood Cancer

By Megan Brooks

June 29, 2019

NEW YORK (Reuters Health) - Children with non-chromosomal birth defects have an increased risk of developing a range of malignancies, although the absolute risk is small, according to a U.S. study of more than 10 million births.

"Currently, we believe it is too early to recommend specific surveillance guidelines for these children," Dr. Philip J. Lupo of Baylor College of Medicine and Texas Children's Cancer and Hematology Centers in Houston told Reuters Health by email.

"This is primarily due to the rarity of childhood cancer. In fact, our results suggest that less than 1% of children with birth defects will develop cancer during childhood or adolescence. Therefore, an important next step in our work will be identifying subsets of children who would benefit most from surveillance," he said.

The association between chromosomal anomalies and cancer is well recognized and a growing number of studies suggest that children with non-chromosomal birth defects may also be at increased risk, Dr. Lupo and colleagues note in JAMA Oncology, online June 20.

They analyzed pooled data on births, birth defects and cancer from Texas, Arkansas, Michigan and North Carolina for children born from 1992 through 2013 and followed until age 18.

Compared with the more than 10 million children without any birth defects, those with chromosomal anomalies (n=539,567) were 11.6 times more likely to be diagnosed with cancer, while children with non-chromosomal birth defects (n=2,123) were 2.5 times more likely to be diagnosed with cancer before age 18 - both significant increases.

"A remarkable finding is the clear gradient in risk of all major classes of cancer (hematologic malignant neoplasms, central nervous system tumors, and non-central nervous system solid tumors) with increasing numbers of birth defects," write the authors of a linked editorial.

Children with four or more major birth defects were 5.9 times more likely to be diagnosed with cancer compared with those with no birth defect. "Children with multiple non-chromosomal birth defects had the highest risk for developing cancer. Future work to identify patterns of children with multiple birth defects and cancer could point to undiagnosed or as-yet-unrecognized cancer syndromes," Dr. Lupo told Reuters Health.

In the analysis of 72 specific birth defect-childhood cancer patterns, the researchers identified 40 that were statistically significant after accounting for multiple comparisons (adjusted P<0.05).

Of note, said Dr. Lupo, hepatoblastoma and neuroblastoma were the cancers most often associated with non-chromosomal defects. "By leveraging this information, we hope to gain new insights into why these cancers occur in children," he told Reuters Health.

"If further validated, our results may inform cancer surveillance protocols for early tumor detection in children with specific birth defects. Future studies should evaluate the molecular features of children with co-occurring birth defects and cancers to further elucidate the mechanisms that lead to these complex outcomes," the authors conclude in their paper.

Editorial writers Dr. Logan Spector of the University of Minnesota Medical School and Dr. Andrew Olshan of the University of North Carolina at Chapel Hill say the clinical implications of the findings are limited for now.

Echoing Dr. Lupo, they say surveillance for cancer "cannot be recommended for most children with birth defects because the absolute risk was far below 1%. It may be worth exploring surveillance for children with 4 or more nonchromosomal birth defects, in whom cumulative risk of cancer was 0.725%. In the future, should the search for causative genes prove fruitful, the detection of a birth defect could trigger genetic testing and surveillance in the presence of high-penetrance variants," they write.

The study, they add, is "another reminder that childhood cancers are diseases of development and of the association between teratogenesis and carcinogenesis. These findings should prompt a robust program of research to understand the origin of cancer risk in children with birth defects and their association with short-term and long-term outcomes of cancer in childhood."

SOURCE: http://bit.ly/2ZG9qnw and http://bit.ly/31T5YrH

JAMA Oncol 2019.

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