Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site

Schraw JM, Sok P, Desrosiers TA, Janitz AE, Langlois PH, Canfield MA, Frazier AL, Plon SE, Lupo PJ, Poynter JN. Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site. Cancer. 2023 Oct 15;129(20):3300-3308. doi: 10.1002/cncr.34906. Epub 2023 Jun 27. PubMed PMID: 37366624; PubMed Central PMCID: PMC10967011.

Studies 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. We evaluated birth defect-GCT associations among N=552 pediatric patients with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and N=6,380 population-based controls without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. We estimated the odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status using unconditional logistic regression. We considered all defects collectively, genetic and chromosomal syndromes, and non-syndromic defects. We stratified by sex, tumor histology (yolk sac tumor, teratoma, germinoma, mixed/other) and location (gonadal, extragonadal, intracranial).Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0%, 2.7% vs. 0.2%, respectively, both p<0.001). In multivariable models, GCT risk was increased among children with birth defects (OR 1.7, CI 1.3–2.4) and syndromic defects (OR 10.4, CI 4.9–22.1). When stratifying by tumor characteristics, birth defects were associated with yolk sac (OR 2.7, CI 1.3–5.0) and mixed/other histologies (OR 2.1, CI 1.2–3.5), and both gonadal (OR 1.7, CI 1.0–2.7) and extragonadal (OR 3.8, CI 2.1–6.5) tumors. Non-syndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females. Our data suggest that syndromic birth defects are at increased risk of pediatric GCTs in males, whereas children with non-syndromic defects are not at increased risk.