Kate A O'Neill1, Michael Fg Murphy2, Kathryn J Bunch2, Susan E Puumala3, Susan E Carozza3, Eric J Chow3, Beth A Mueller3, Colleen C McLaughlin3, Peggy Reynolds3, Tim J Vincent3, Julie Von Behren3, Logan G Spector3. 1. Department of Paediatrics, Nuffield Department of Obstetrics and Gynaecology, National Perinatal Epidemiology Unit, Formerly of the Childhood Cancer Research Group, University of Oxford, Oxford, UK, Sanford Research Center, Sioux Falls, SD, USA, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, New York State Department of Health, Albany, NY, USA, Cancer Prevention Institute of California, Berkeley, CA, USA and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA Department of Paediatrics, Nuffield Department of Obstetrics and Gynaecology, National Perinatal Epidemiology Unit, Formerly of the Childhood Cancer Research Group, University of Oxford, Oxford, UK, Sanford Research Center, Sioux Falls, SD, USA, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, New York State Department of Health, Albany, NY, USA, Cancer Prevention Institute of California, Berkeley, CA, USA and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA kate.oneill@paediatrics.ox.ac.uk. 2. Department of Paediatrics, Nuffield Department of Obstetrics and Gynaecology, National Perinatal Epidemiology Unit, Formerly of the Childhood Cancer Research Group, University of Oxford, Oxford, UK, Sanford Research Center, Sioux Falls, SD, USA, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, New York State Department of Health, Albany, NY, USA, Cancer Prevention Institute of California, Berkeley, CA, USA and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA Department of Paediatrics, Nuffield Department of Obstetrics and Gynaecology, National Perinatal Epidemiology Unit, Formerly of the Childhood Cancer Research Group, University of Oxford, Oxford, UK, Sanford Research Center, Sioux Falls, SD, USA, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, New York State Department of Health, Albany, NY, USA, Cancer Prevention Institute of California, Berkeley, CA, USA and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. 3. Department of Paediatrics, Nuffield Department of Obstetrics and Gynaecology, National Perinatal Epidemiology Unit, Formerly of the Childhood Cancer Research Group, University of Oxford, Oxford, UK, Sanford Research Center, Sioux Falls, SD, USA, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, New York State Department of Health, Albany, NY, USA, Cancer Prevention Institute of California, Berkeley, CA, USA and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
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.
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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