Journal
CANCER EPIDEMIOLOGY
Volume 57, Issue -, Pages 7-12Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.canep.2018.09.002
Keywords
Childhood cancer; Sex-disparity; Birthweight; Mediation analysis
Funding
- National Institutes of Health [T32 CA099936, N01 CN05230]
- Children's Cancer Research Fund, Minneapolis, MN
- Centers for Disease Control and Prevention's National Program of Cancer Registries [U58 DP000783-01]
- Fred Hutchinson Cancer Research Center
- DIVISION OF CANCER PREVENTION AND CONTROL [N01CN005230] Funding Source: NIH RePORTER
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P2CHD041023] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [T32CA099936] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR CHRONIC DISEASE PREV AND HEALTH PROMO [U58DP000783] Funding Source: NIH RePORTER
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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.
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