Paediatric germ cell tumours and congenital abnormalities: a Children's Oncology Group study

Abstract

METHODS: Maternally reported congenital abnormalities (CAs) were examined in a case -control study of 278 cases of paediatric germ cell tumours (GCTs) and 423 controls. RESULTS AND CONCLUSIONS: Germ cell tumours were significantly associated with cryptorchidism in males (OR ¼ 10.8, 95% CI: 2.1 -55.1), but not with any other specific CA in either sex. The risk factors for paediatric germ cell tumours (GCTs), which comprise a histologically heterogeneous group of tumours affecting an estimated 360 individuals o15 years of age each year in the United States (Bernstein et al, 1999; US Census Bureau, 2007), have not been well described (Bernstein et al, 1999). However, congenital abnormalities (CAs) have often been reported in association with GCTs in case series and in record linkage studies (Li and Fraumeni, 1972;Fraumeni et al, 1973;Li et al, 1973;Birch et al, 1982;Mann et al, 1993;Altmann et al, 1998;Little, 1999;Nishi et al, 2000;Merks et al, 2005;Bjorge et al, 2008;Rankin et al, 2008). The presence of cryptorchidism is a confirmed risk factor for testicular GCTs in men (Sarma et al, 2006), but its association with paediatric GCTs has not been as well studied. We evaluated the association between certain CAs and childhood GCTs by sex, age at diagnosis, anatomical location, and histology in a Children's Oncology Group (COG) study. MATERIALS AND METHODSThe study protocol was approved by the Institutional Review Boards of the University of Minnesota and by the participating COG institutions. Details regarding this study have been described previously (Chen et al, 2005). Briefly, GCT cases with malignant extracranial tumours, diagnosed from the time of birth to 14 years of age between 1 January 1993 and 31 December 2001, were ascertained from US and Canadian COG hospitals. Eligible diagnoses were dysgerminoma-seminoma-germinoma, embryonal carcinoma, yolk sac tumour, choriocarcinoma, malignant teratoma, and mixed GCTs. Controls were recruited through random digit dialling, and frequency was matched to cases on sex and birth year ± 1 year, at ratios of approximately 1 : 2 for males and 1 : 1 for females. Cases and controls were eligible if they had a telephone in their residence and if their biological mother spoke English and consented to an interview. Participation rates were 81 and 67% for cases and controls, respectively. Exposure information was collected from mothers by telephone interview, including the seven CA categories shown in Table 3. Statistical analysesWe used SAS version 9.1. (SAS Institute Inc., Cary, NC, USA) to conduct statistical analyses. Statistical differences in the frequency or means of sociodemographic and infant characteristics between cases and controls were assessed using Mantel -Haenszel w 2 tests and one-way analysis of variance. We used unconditional logistic regression to examine the associations between CAs and GCTs, adjusting for the matching factors, sex and child's age. We conducted analyses stratified by sex, age at diagnosis (p2, 42 years), tumour histology, and anatomical locat...

Trends in incidence and survival of pediatric and adolescent patients with germ cell tumors in the United States, 1975 to 2006

“…Evidence suggests that at least some risk factors, such as cryptorchidism 47, 48 , overlap for pediatric and adult testicular GCTs; however, the distinct clinical 3, 19, 49, 50 and genetic profiles 51-53 of pediatric and adult GCTs provide support for distinct etiologies. Several mechanisms have been hypothesized for the increase in testicular GCTs in males, with much attention focused on exposure to estrogens and environmental hormone disruptors 54 ; however, the exact mechanism is not clear.…”

Unusual coexistence of a renal anomaly and germ cell tumor: An embryonal happenstance?

“…[2] There is no documented literature on any other association of gonadal or EGGCT with congenital abnormalities. The HSK is the most common type of renal fusion anomaly and can be related to teratogenic events affecting the urinary system (Wilms tumor and carcinoid tumors).…”

“…The HSK is the most common type of renal fusion anomaly and can be related to teratogenic events affecting the urinary system (Wilms tumor and carcinoid tumors). [2] Kidney is one of the least common locations for EGGCT teratomas, with only one case report of a child with HSK and intrarenal teratoma. [3]…”

“…[1] EGGCT non-seminomatous tumors have been associated with Klinefelter syndrome (20%)[2] but rarely with other congenital anomalies. We describe an unusual case of a young adult who presented with EGGCT and a horseshoe kidney (HSK) and was successfully treated with chemotherapy, surgery and repeat surgery for a recurrent mass.…”

Pediatric germ cell tumors and parental infertility and infertility treatment: A Children's Oncology Group report

“…Congenital abnormalities of the genital organs have been found to be associated with childhood GCT [5, 6, 8, 11] and studies have indicated increased risk of these abnormalities following intracytoplasmic sperm injection (ICSI) [14, 15]. Another study noted an increased risk of cryptorchidism after intrauterine insemination, although there was no increase after in vitro fertilization or ICSI [16].…”