Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Cancer. 2023 Oct 15;129(20):3300-3308. doi: 10.1002/cncr.34906. Epub 2023 Jun 27.
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.
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).
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.
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.
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.
研究报告称，生殖细胞肿瘤（GCT）患儿的出生缺陷发生率增加。然而，很少有研究通过性别、缺陷类型或肿瘤特征来评估相关性。
对 552 名患有 GCT 的儿科患者（GCT 组）和 6380 名无癌症的儿童（对照组）进行了出生缺陷与 GCT 关系的评估，这些儿童来自于儿童癌症中的遗传重叠：畸形与癌症研究。使用非条件逻辑回归估计 GCT 与出生缺陷状态的比值比（OR）和 95%置信区间（CI）。所有缺陷均被视为整体，分为遗传和染色体综合征及非综合征缺陷。按性别、肿瘤组织学（卵黄囊瘤、畸胎瘤、生殖细胞瘤和混合/其他）和位置（性腺、性腺外和颅内）进行分层。
GCT 病例的出生缺陷和综合征缺陷比对照组更常见（6.9%比 4.0%和 2.7%比 0.2%，均<0.001）。在多变量模型中，有出生缺陷的儿童患 GCT 的风险增加（OR，1.7；95%CI，1.3-2.4）和综合征缺陷（OR，10.4；95%CI，4.9-22.1）。按肿瘤特征分层时，出生缺陷与卵黄囊瘤（OR，2.7；95%CI，1.3-5.0）和混合/其他组织学（OR，2.1；95%CI，1.2-3.5）以及性腺肿瘤（OR，1.7；95%CI，1.0-2.7）和性腺外肿瘤（OR，3.8；95%CI，2.1-6.5）相关。非综合征缺陷与 GCT 无明显相关性。在性别分层分析中，仅在男性中观察到相关性，而在女性中未观察到相关性。
这些数据表明，患有综合征性出生缺陷的男性患儿童 GCT 的风险增加，而患有非综合征性缺陷的男性和女性的风险则未增加。
