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

Kate A. O'Neill, Michael F G Murphy, Kathryn J. Bunch, Susan E. Puumala, Susan E. Carozza, Eric J. Chow, Beth A. Mueller, Colleen C. McLaughlin, Peggy Reynolds, Tim J. Vincent, Julie Von Behren, Logan G. Spector

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)153-168
Number of pages16
JournalInternational journal of epidemiology
Volume44
Issue number1
DOIs
StatePublished - Feb 1 2015

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Case-Control Studies
Population
Neoplasms
Leukemia
Central Nervous System Neoplasms
Birth Order
Retinoblastoma
Germ Cell and Embryonal Neoplasms
Maternal Age
Neuroblastoma
Sarcoma
Gestational Age
Registries
Melanoma
Lymphoma
Odds Ratio
Parturition
Confidence Intervals
Kidney
Bone and Bones

Keywords

  • Birthweight
  • Case-control study
  • Childhood cancer
  • Intrauterine growth

Cite this

Infant birthweight and risk of childhood cancer : International population-based case control studies of 40 000 cases. / O'Neill, Kate A.; Murphy, Michael F G; Bunch, Kathryn J.; Puumala, Susan E.; Carozza, Susan E.; Chow, Eric J.; Mueller, Beth A.; McLaughlin, Colleen C.; Reynolds, Peggy; Vincent, Tim J.; Behren, Julie Von; Spector, Logan G.

In: International journal of epidemiology, Vol. 44, No. 1, 01.02.2015, p. 153-168.

Research output: Contribution to journalArticle

O'Neill, KA, Murphy, MFG, Bunch, KJ, Puumala, SE, Carozza, SE, Chow, EJ, Mueller, BA, McLaughlin, CC, Reynolds, P, Vincent, TJ, Behren, JV & Spector, LG 2015, 'Infant birthweight and risk of childhood cancer: International population-based case control studies of 40 000 cases', International journal of epidemiology, vol. 44, no. 1, pp. 153-168. https://doi.org/10.1093/ije/dyu265
O'Neill, Kate A. ; Murphy, Michael F G ; Bunch, Kathryn J. ; Puumala, Susan E. ; Carozza, Susan E. ; Chow, Eric J. ; Mueller, Beth A. ; McLaughlin, Colleen C. ; Reynolds, Peggy ; Vincent, Tim J. ; Behren, Julie Von ; Spector, Logan G. / Infant birthweight and risk of childhood cancer : International population-based case control studies of 40 000 cases. In: International journal of epidemiology. 2015 ; Vol. 44, No. 1. pp. 153-168.
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AU - Puumala, Susan E.

AU - Carozza, Susan E.

AU - Chow, Eric J.

AU - Mueller, Beth A.

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N2 - 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.

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