Affiliation:
1. Section of Hematology‐Oncology Department of Pediatrics Baylor College of Medicine Houston Texas USA
2. Department of Epidemiology Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
3. Department of Biostatistics and Epidemiology Hudson College of Public Health University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA
4. Division of Epidemiology, Human Genetics and Environmental Sciences University of Texas School of Public Health Austin Texas USA
5. Birth Defects Epidemiology and Surveillance Branch Texas Department of State Health Services Austin Texas USA
6. Department of Pediatrics Harvard Medical School Boston Massachusetts USA
7. Department of Pediatric Oncology Dana‐Farber Cancer Institute Boston Massachusetts USA
8. Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas USA
9. Department of Pediatrics University of Minnesota Minneapolis Minnesota USA
Abstract
AbstractBackgroundStudies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics.MethodsBirth defect–GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population‐based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial).ResultsBirth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3–2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9–22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3–5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2–3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0–2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1–6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex‐stratified analyses, associations were observed among males but not females.ConclusionsThese data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereas males with nonsyndromic defects and females are not at an increased risk.Plain Language Summary
We investigated whether birth defects (such as congenital heart disease or Down syndrome) are linked to childhood germ cell tumors (GCTs), cancers that mainly develop in the ovaries or testes.
We studied different types of birth defects (defects that were caused by chromosome changes such as Down syndrome or Klinefelter syndrome and defects that were not) and different types of GCTs.
Only chromosome changes such as Down syndrome or Klinefelter syndrome were linked to GCTs.
Our study suggests that most children with birth defects are not at an increased risk of GCTs because most birth defects are not caused by chromosome changes.
Funder
U.S. Department of Defense