Background: High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. Methods: We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. Results: Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. Conclusions: Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.
Bibliographical noteFunding Information:
This work was supported by Children with Cancer UK [grant number 2006/044 to M.M.] and the Daphne Jackson Trust/ GlaxoSmithKline R & D (research fellowship to K.O.). The Childhood Cancer Research Group (CCRG) was also supported by the Department of Health for England and Wales and the Scottish Government. Compilation of the US data was supported by the Children’s Cancer Research Fund, Minneapolis, MN; the California Department of Health Services (California registry data); the Centers for Disease Control and Prevention by Cooperative Agreement (California, New York and Washington registry data); the Fred Hutchinson Cancer Research Center and the Centers for Disease Control National Program of Cancer Registries (Washington cancer registry data); the Washington State Department of Health (Washington vital records data); and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (California registry data and Washington cancer registry data).
- Case-control study
- Childhood cancer
- Intrauterine growth