Epidemiology of Germ Cell Tumors

Pankratz

Lane

et al. 2018

Cancer

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Background Males with Klinefelter syndrome (KS; 47, XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. There are no reports characterizing the prevalence of KS among male GCT cases. Methods We used array genotyping data from a Children’s Oncology Group epidemiology study to estimate the prevalence of KS in males with GCTs (n=433; aged 0–19 years). Using Fisher’s exact tests, we examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and a number of birth characteristics between KS-GCT cases and GCT cases without chromosomal abnormalities. Using publicly available data, we estimated the 1-year risk, risk ratio (RR), and corresponding 95% confidence interval (95% CI) of GCTs among KS cases. Results Based on analysis of array genotyping data, 3% (n=13) of male GCT cases had KS. The additional X chromosome was of maternal origin in7/13 cases. Of these 13 KS cases, 5/9 (56%) KS-GCT cases with parental questionnaire data reported a diagnosis of KS. We did not observe significant differences in patient or birth characteristics between KS-GCT and non-KS-GCT cases. KS-GCT cases were significantly more likely to be diagnosed with mediastinal tumors than non-KS-GCT cases (p<0.01). We estimated the risk of developing a GCT among males with KS to be 0.00025, or 1/4,000 (RR: 18.8; 95% CI: 11.7, 30.0). Conclusions Compared to males without chromosomal abnormalities, KS males are more likely to be diagnosed with a mediastinal GCT. The presence of KS should be considered in males with a diagnosis of mediastinal GCT.

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confidence: 94%

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confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Klinefelter syndrome in males with germ cell tumors: A report from the Children's Oncology Group

Pankratz

Lane

et al. 2018

Cancer

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Survival differences by race/ethnicity among children and adolescents diagnosed with germ cell tumors

Frazier

Poynter

2019

Intl Journal of Cancer

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Survival differences by racial and ethnic group have been reported in children and adolescents with germ cell tumors (GCTs), but whether these differences depend on stage of disease is unclear. Using the SEER 18 registries (2000–2015), we examined GCT survival differences by race/ethnicity (non‐Hispanic white [NHW], Black, Asian/Pacific Islander [API], Hispanic) separately for males and females aged 0–19 years at diagnosis. We used Kaplan–Meier survival curves (Log‐Rank p values) to characterize survival differences. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between race/ethnicity and death. Using an inverse odds weighting mediation analysis, we estimated the association between race/ethnicity and death treating stage of disease as the mediator. There were no significant racial/ethnic survival differences among females. Male survival differed by race/ethnicity (p < 0.0001) with NHW males having the best survival. Compared to NHW, API and Hispanic males had significantly higher risks of death (API HR: 2.18; 95% CI: 1.32–3.56; Hispanic HR: 1.98; 95% CI: 1.42–2.78) (model adjusted for age and year at diagnosis, tumor histology and location, stage). This association was mediated by stage of disease only among Hispanic males with gonadal tumors (indirect HR: 1.18; 95% CI: 1.03–1.35). The increased risk of death after a testicular GCT diagnosis observed among Hispanic males was mediated by stage of disease. For API males and Hispanic males with extragonadal tumors, other unidentified factors including differences in exposures, tumor biology or treatment received may impact the observed racial/ethnic survival disparities.

The association between sex and most childhood cancers is not mediated by birthweight

Richardson

Kehm

et al. 2018

Cancer Epidemiology

Background Male sex is associated with an increased risk of childhood cancer as is high birthweight. Given that sex determination precedes birthweight we conducted a mediation analysis to estimate the direct effect of sex in association with childhood cancer tumor type with birthweight as the mediator. Methods Cases (n=12,632) and controls (n=64,439) (ages 0–14 years) were identified from population-based cancer and birth registries in Minnesota, New York, and Washington states (1970–2014). An inverse odds weighting (IOW) mediation analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between sex and cancer. Results A significant indirect effect was observed for sex and lymphoid leukemia, mediated by birthweight (indirectOR: 1.03; 95% CI: 1.02–1.04). We observed significant direct effects for male sex and lymphoid leukemia (directOR: 1.16; 95% CI: 1.08–1.25), Hodgkin lymphoma (directOR: 1.48; 95% CI: 1.22–1.81), Burkitt lymphoma (directOR: 5.02; 95% CI: 3.40–7.42), other non- Hodgkin lymphoma (directOR: 1.42; 95% CI: 1.18–1.70), intracranial embryonal tumors (directOR: 1.49; 95% CI: 1.26–1.76), hepatoblastoma (directOR: 1.90; 95% CI: 1.40–2.59), and rhabdomyosarcoma (directOR: 1.47; 95% CI: 1.19–1.81). There were also inverse associations for extracranial GCTs (directOR: 0.41; 95% CI: 0.26–0.63) and thyroid carcinoma (directOR: 0.35; 95% CI: 0.25–0.50). Conclusion Significant direct effects for sex and numerous childhood cancer types suggests sex- specific factors such as differences in gene expression from the autosomes or the X chromosome, rather than birthweight, may underlie sex differences in tumor risk.