In the Journals

Birth defects linked to increased risk for childhood cancer

Certain birth defects appeared significantly associated with increased risk for childhood cancer, according to results of a population-based cohort study of more than 10 million births published in JAMA Oncology.

Additionally, results showed a higher number of nonchromosomal birth defects corresponded with increased risk for cancer before age 18 years, although the absolute risk remained less than 1%.

“Despite the recognized association between birth defects and childhood cancers in general, the ability to identify associations between specific birth defects and specific cancer subtypes has been limited in previous studies by insufficient sample size given the relative infrequency of these diagnoses,” Philip J. Lupo, PhD, associate professor of pediatrics and hematology-oncology at Baylor College of Medicine, and colleagues wrote. “In addition, findings from previous studies suggest there may be an association between the number of birth defects per child and cancer risk, but larger populations are needed to better investigate the extent to which having multiple birth defects is associated with increased risk.”

In the multistate, population-based registry linkage study, Lupo and colleagues pooled statewide data on more than 10 million children born in Texas, Arkansas, Michigan and North Carolina between 1992 and 2013. Data linkages in each state produced four study groups: children with neither a birth defect (including chromosomal abnormalities and nonchromosomal birth defects) nor cancer; children with a birth defect but without cancer; children without a birth defect but with cancer; and children with a birth defect and cancer.

Cancer diagnosis before age 18 years as documented in the registries served as the study’s main outcome. The researchers used Cox regression models to determine HRs and 95% CIs to assess correlations between birth defects and childhood cancer, as well as between the number of nonchromosomal defects and cancer risk.

Median follow-up was 8.5 years for children without birth defects and 8.1 years for children with birth defects.

More than 530,000 children overall were diagnosed with a minimum of one birth defect.

Results showed a 11.6 (95% CI, 10.4-12.9) times greater likelihood of cancer diagnosis in childhood or adolescence among children with chromosomal anomalies vs. those without birth defects. Children with nonchromosomal birth defects (n = 2,123) demonstrated a 2.5 (95% CI, 2.4-2.6) times greater likelihood of cancer diagnosis before age 18 years.

Researchers observed associations between a higher number of nonchromosomal birth defects and increased risk for cancer. Children with four or more major birth defects demonstrated a 5.9 (95% CI, 5.4-6.5) times greater likelihood of cancer diagnosis than those with no defect.

An analysis of 72 specific birth defect-childhood cancer patterns revealed 40 statistically significant HRs (adjusted P < .05) after accounting for several comparisons. Hepatoblastoma and neuroblastoma were most often linked to nonchromosomal defects.

The researchers cited several study limitations, including lack of uniformity in birth defect surveillance procedures and the possibility of identifying birth defects during diagnostic evaluation of children with cancer.

The current study identifies an important correlation between two “diseases of development” among children, according to a related editorial by Logan G. Spector, PhD, division director and professor of pediatric epidemiology and clinical research at University of Minnesota Medical School, and Andrew F. Olshan, PhD, Barbara Sorenson Hulka distinguished professor in cancer epidemiology in the department of epidemiology at Gillings School of Global Public Health at The University of North Carolina at Chapel Hill.

“As it is said, the first step to solving a problem is recognizing it. With this study, Lupo [and colleagues] have recognized a problem and described it in fine detail,” Spector and Olshan wrote. “These results should be of interest to clinicians caring for children with birth defects and especially to pediatric oncologists. Moreover, the study 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.” – by Jennifer Byrne

Disclosures: Lupo reports grants from the Cancer Prevention & Research Institute of Texas and from Alex’s Lemonade Stand Foundation during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures. Spector and Olshan report no relevant financial disclosures.

Certain birth defects appeared significantly associated with increased risk for childhood cancer, according to results of a population-based cohort study of more than 10 million births published in JAMA Oncology.

Additionally, results showed a higher number of nonchromosomal birth defects corresponded with increased risk for cancer before age 18 years, although the absolute risk remained less than 1%.

“Despite the recognized association between birth defects and childhood cancers in general, the ability to identify associations between specific birth defects and specific cancer subtypes has been limited in previous studies by insufficient sample size given the relative infrequency of these diagnoses,” Philip J. Lupo, PhD, associate professor of pediatrics and hematology-oncology at Baylor College of Medicine, and colleagues wrote. “In addition, findings from previous studies suggest there may be an association between the number of birth defects per child and cancer risk, but larger populations are needed to better investigate the extent to which having multiple birth defects is associated with increased risk.”

In the multistate, population-based registry linkage study, Lupo and colleagues pooled statewide data on more than 10 million children born in Texas, Arkansas, Michigan and North Carolina between 1992 and 2013. Data linkages in each state produced four study groups: children with neither a birth defect (including chromosomal abnormalities and nonchromosomal birth defects) nor cancer; children with a birth defect but without cancer; children without a birth defect but with cancer; and children with a birth defect and cancer.

Cancer diagnosis before age 18 years as documented in the registries served as the study’s main outcome. The researchers used Cox regression models to determine HRs and 95% CIs to assess correlations between birth defects and childhood cancer, as well as between the number of nonchromosomal defects and cancer risk.

Median follow-up was 8.5 years for children without birth defects and 8.1 years for children with birth defects.

More than 530,000 children overall were diagnosed with a minimum of one birth defect.

Results showed a 11.6 (95% CI, 10.4-12.9) times greater likelihood of cancer diagnosis in childhood or adolescence among children with chromosomal anomalies vs. those without birth defects. Children with nonchromosomal birth defects (n = 2,123) demonstrated a 2.5 (95% CI, 2.4-2.6) times greater likelihood of cancer diagnosis before age 18 years.

Researchers observed associations between a higher number of nonchromosomal birth defects and increased risk for cancer. Children with four or more major birth defects demonstrated a 5.9 (95% CI, 5.4-6.5) times greater likelihood of cancer diagnosis than those with no defect.

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An analysis of 72 specific birth defect-childhood cancer patterns revealed 40 statistically significant HRs (adjusted P < .05) after accounting for several comparisons. Hepatoblastoma and neuroblastoma were most often linked to nonchromosomal defects.

The researchers cited several study limitations, including lack of uniformity in birth defect surveillance procedures and the possibility of identifying birth defects during diagnostic evaluation of children with cancer.

The current study identifies an important correlation between two “diseases of development” among children, according to a related editorial by Logan G. Spector, PhD, division director and professor of pediatric epidemiology and clinical research at University of Minnesota Medical School, and Andrew F. Olshan, PhD, Barbara Sorenson Hulka distinguished professor in cancer epidemiology in the department of epidemiology at Gillings School of Global Public Health at The University of North Carolina at Chapel Hill.

“As it is said, the first step to solving a problem is recognizing it. With this study, Lupo [and colleagues] have recognized a problem and described it in fine detail,” Spector and Olshan wrote. “These results should be of interest to clinicians caring for children with birth defects and especially to pediatric oncologists. Moreover, the study 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.” – by Jennifer Byrne

Disclosures: Lupo reports grants from the Cancer Prevention & Research Institute of Texas and from Alex’s Lemonade Stand Foundation during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures. Spector and Olshan report no relevant financial disclosures.