Sex differences in associations between birth characteristics and childhood cancers: a five-state registry-linkage study

Background: There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. Methods: Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction < 0.01) by sex was evaluated for each characteristic in each cancer. Results: Males comprised > 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction < 0.01) including gestational age for ALL (female, 40 vs. 37–39 weeks OR: 0.84, 95% CI 0.73–0.97) and ependymoma (female, 40 vs. 37–39 OR: 1.78, 95% CI 1.14–2.79; female, ≥ 41 OR: 2.01. 95% CI 1.29–3.14), birth order for AML (female, ≥ 3rd vs. 1st OR: 1.39, 95% CI 1.01–1.92), maternal education for Hodgkin lymphoma (male, any college vs. < high school[HS] OR: 1.47, 95% CI 1.03–2.09) and Wilms tumor (female, any college vs. HS OR: 0.74, 95% CI 0.59–0.93), maternal race/ethnicity for neuroblastoma (male, black vs. white OR: 2.21, 95% CI 1.21–4.03; male, Hispanic vs. white OR: 1.86, 95% CI 1.26–2.75; female, Asian/Pacific Islander vs. white OR: 0.28, 95% CI 0.12–0.69), and paternal age (years) for hepatoblastoma in males (< 24 vs. 25–29 OR: 2.17, 95% CI 1.13–4.19; ≥ 35 vs. 25–29 OR: 2.44, 95% CI 1.28–4.64). Conclusions: These findings suggest etiologic heterogeneity by sex for childhood cancers for gestational age, maternal education, and race/ethnicity and paternal age.