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

Lindsay A. Williams, Jeannette Sample, Colleen C. McLaughlin, Beth A. Mueller, Eric J. Chow, Susan E. Carozza, Peggy Reynolds, Logan G. Spector

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1289-1298
Number of pages10
JournalCancer Causes and Control
Issue number11
StatePublished - Nov 2021

Bibliographical note

Funding Information:
The Children’s Cancer Research Fund (LAW), the Washington State Cancer Registry and the Cancer Surveillance System of Western Washington, which provided data, are supported by contract N01-CN-05230 from the National Cancer Institute and the Fred Hutchinson Cancer Research Center. In California and Texas, National Cancer Institute grants R01 CA717450 and R01 CA92670 supported assembly of their respective datasets. In New York, partial support for assembly of the dataset was received from the Centers for Disease Control and Prevention’s National Program of Cancer Registries by cooperative agreement U58DP000783-01 awarded to the New York State Department of Health; contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.


  • Etiologic heterogeneity
  • Pediatric cancer
  • Registry-based study
  • Sex differences


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