Philip J Lupo1,2, Jeremy M Schraw3, Tania A Desrosiers4, Wendy N Nembhard5,6, Peter H Langlois7, Mark A Canfield7, Glenn Copeland8, Robert E Meyer9, Austin L Brown1,2, Tiffany M Chambers1,2, Pagna Sok1,2, Heather E Danysh1,2, Susan E Carozza10, Saumya D Sisoudiya11, Susan G Hilsenbeck12, Amanda E Janitz13, Matthew E Oster14, Angela E Scheuerle7,15, Joshua D Schiffman16, Chunqiao Luo5, Amir Mian17, Beth A Mueller18, Chad D Huff19, Sonja A Rasmussen20,21, Michael E Scheurer1,2, Sharon E Plon1,2,11. 1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas. 2. Texas Children's Cancer Center, Texas Children's Hospital, Houston. 3. Department of Medicine, Baylor College of Medicine, Houston, Texas. 4. Department of Epidemiology, University of North Carolina at Chapel Hill. 5. Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock. 6. Arkansas Children's Research Institute, Little Rock. 7. Birth Defects Epidemiology and Surveillance Branch,Texas Department of State Health Services, Austin. 8. Division for Vital Records and Health Statistics, Michigan Department of Health and Human Services, Lansing, Michigan. 9. Department of Maternal and Child Health, University of North Carolina at Chapel Hill. 10. School of Biological and Population Health Sciences, Oregon State University, Corvallis. 11. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. 12. Smith Breast Center, Baylor College of Medicine, Houston, Texas. 13. Department of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City. 14. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia. 15. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas. 16. Division of Hematology and Oncology, Department of Pediatrics, Huntsman Cancer Institute, University of Utah, Salt Lake City. 17. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock. 18. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 19. Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas. 20. Department of Pediatrics, University of Florida College of Medicine Gainsville. 21. Department of Epidemiology, University of Florida College of Medicine and College of Public Health and Health Professions, Gainesville.
Abstract
IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.
IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.
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Authors: Jian-Rong He; Jane E Hirst; Gabriella Tikellis; Gary S Phillips; Rema Ramakrishnan; Ora Paltiel; Anne-Louise Ponsonby; Mark Klebanoff; Jørn Olsen; Michael F G Murphy; Siri E Håberg; Stanley Lemeshow; Sjurdur F Olsen; Xiu Qiu; Per Magnus; Jean Golding; Mary H Ward; Joseph L Wiemels; Kazem Rahimi; Martha S Linet; Terence Dwyer Journal: Int J Epidemiol Date: 2022-06-13 Impact factor: 9.685
Authors: Amanda E Janitz; Hanh Dung Dao; Janis E Campbell; Julie A Stoner; Jennifer D Peck Journal: Birth Defects Res Date: 2019-12-10 Impact factor: 2.344
Authors: Jeremy M Schraw; Tania A Desrosiers; Wendy N Nembhard; Peter H Langlois; Robert E Meyer; Mark A Canfield; Sonja A Rasmussen; Tiffany M Chambers; Logan G Spector; Sharon E Plon; Philip J Lupo Journal: Cancer Date: 2020-05-29 Impact factor: 6.860