Associations Between Birth Defects and Childhood and Adolescent Germ Cell Tumors According to Sex, Histologic Subtype, and Site

Authors

Jeremy M Schraw
Pagna Sok
Tania A Desrosiers
Amanda E Janitz
Peter H Langlois
Mark A Canfield
A Lindsay Frazier
Sharon E Plon
Philip J Lupo
Jenny N Poynter

Publication Date

10-15-2023

Journal

Cancer

DOI

10.1002/cncr.34906

PMID

37366624

PMCID

PMC10967011

PubMedCentral® Posted Date

10-15-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Male, Child, Humans, Adolescent, Klinefelter Syndrome, Down Syndrome, Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, germ cell tumors, childhood cancer, birth defects, cancer predisposition, epidemiology

Abstract

BACKGROUND: 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.

METHODS: Birth 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).

RESULTS: Birth 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.

CONCLUSIONS: These 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.