Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases

This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Oxford University Press on behalf of the International Epidemiological Association. The published article can be found at: http://ije.oxfordjournals.org/.Background: High birthweight is an established risk factor for childhood leukaemia.\ud Its association with other childhood cancers is less clear, with studies hampered by low\ud case numbers. Methods: We used two large independent datasets to explore risk associations between\ud birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls\ud were obtained by linkage of birth to cancer registration records across five US\ud states, and 23 772 cases and 33 206 controls were obtained from the UK National\ud Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age,\ud 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\ud interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia\ud [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system\ud [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK:\ud 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\ud 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\ud high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant\ud melanomas. For some cancer subtypes, risk associations with birthweight were\ud non-linear. We observed no association between birthweight and risk of retinoblastoma\ud or bone tumours. Conclusions: Approximately half of all childhood cancers exhibit associations with\ud birthweight. The apparent independence from other factors indicates the importance\ud of intrauterine growth regulation in the aetiology of these diseases