Higher Birthweight Linked to Increased Childhood Cancer Risk

MedicalResearch.com Interview with:
Kate A O’Neill

Department of Paediatrics
University of Oxford Children’s Hospital
John Radcliffe Hospital Oxford UK

MedicalResearch.com: What is the background for this study?

Dr. O’Neill: Cancer affects around 1 in 500 children under the age of 15. Although the diagnosis and treatment of these diseases have seen major advances over the past few decades, survivors often experience health complications later in life, and cancer remains the main cause of disease related death in children in the developed world.

The identification of risk factors for a number of adult cancers has allowed awareness and screening campaigns aimed at preventing disease. For the majority of childhood cancers, however, we still do not know what causes them, and so similar preventative measures are at present not possible.

Incidence rates for many childhood cancers peak within the first few years of life, suggesting that the causative events occur early. For childhood leukaemia, it has even been shown that pre-malignant cells are already present at birth, indicating the disease may originate in utero. Studies exploring potential prenatal risk factors for childhood leukaemia have consistently found that children with the disease have higher birthweights than children who do not, and it is now widely accepted that the faster a foetus grows, the higher the risk of developing leukaemia in childhood.

Leukaemia is the most common childhood cancer, accounting for approximately one third of all cases. Other childhood cancers are rarer, and it is consequently harder to perform similar risk association studies. The aim of this study was to compile information on large enough numbers of cases and controls to allow the analysis of risk associations between birthweight and all types of childhood cancer. Furthermore, we compiled data in different countries (USA and UK) to allow the comparison of results from two independent populations.

MedicalResearch.com: What are the main findings?

Dr. O’Neill: We found that with each 0.5kg (1.1lb) increase in birthweight, the risk of childhood cancer increased by 6%. Compared to babies with average birthweights (3-3.49kg, or 6.6lb -7.7lb), babies with clinically high birthweights (4kg, or 8.8lb, and above) had an increased risk of between 16% and 20%.

These increased risks were strongest for certain cancers:

  • Leukaemias
  • Tumours of the central nervous system
  • Renal tumours
  • Soft tissue sarcoma
  • Neuroblastoma
  • Lymphoma
  • Germ cell tumours
  • Malignant melanomas

Hepatic tumours showed the reverse association, with risk increasing as birthweight decreased. Retinoblastoma, an embryonal tumour, and malignant bone tumours, which occur predominantly in adolescents, did not associate with birthweight.

Our results were strikingly similar between USA and UK populations. Furthermore, birthweight appeared act independently of other factors that are known or suspected to associate with birthweight and/or childhood cancer (gestational age, birth order, plurality, maternal age and race/ethnicity).

In summary, we found that approximately half of all childhood cancers are associated with birthweight. The association with a diversity of otherwise unrelated cancers indicates that in utero tissue growth and development has an underlying and potentially key role in the development of malignancy in childhood.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. O’Neill: It is important that our results are taken in the context of overall risks. Childhood cancer is a relatively rare disease, and our data indicate that for a baby with a high birthweight, the risk of developing cancer in childhood is only increased from 1 in 500 to 1 in 400. However, it may be beneficial for health professionals to be aware of these increased risks. For example, a clinician may wish to consider the birthweight of a child showing potential signs of cancer, as a high or low birthweight may justify early testing for disease.

In the wider context of public health, the finding that high birthweight increases the risk of such a large proportion of childhood cancers may be cause for concern. Over the last few decades, trends in birthweight have been accompanied by trends in childhood cancer incidence, and our results would suggest that the two are interrelated. Now that we are in the midst of an obesity epidemic, the number of overweight and obese women of childbearing age is on the increase, and these women have been shown to be up to twice as likely to give birth to babies with high birthweights. So in addition to the detriment of the health of the adult population, rising obesity levels may also be putting their children at higher risk of cancer.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. O’Neill: The big question now is “why?”. We do not know why growth in utero influences the risk of cancer in childhood. For leukaemia, a popular theory is that faster growing or bigger babies are exposed to higher levels of growth hormones, which can have oncogenic effects on the developing immune system. Oestrogen levels during pregnancy, which have also been shown to positively correlate with birthweight, may also increase the risk of malignancy. Or there may be a genetic explanation, if particular genetic variants of these, or other, growth regulatory genes increase the rate of foetal growth as well as susceptibility to cancer.

Our study shows that birthweight affects the risk of a diversity of pathologically unrelated cancers, so the biological mechanism driving this must affect a diversity of cell types. Levels of growth or sex hormones and/or genetic variation can affect multiple cell types, so the theories proposed for leukaemia may also hold true for the cancer types indicated in our study. Or there may be a more simple explanation: the risk of cancer is related to the number of susceptible cells in the foetus or newborn. The heavier the baby, the larger the pool of cells, and thus the greater the risk of oncogenic insult. This could also be organ specific, perhaps risk of a particular cancer correlates with the size of the corresponding organ. There is some evidence for this with brain tumours, where risk has been shown to increase with head circumference at birth.

Future research will hopefully focus on measuring these parameters and looking for correlations with disease. That such studies would have to be prospective, measuring at birth and waiting to observe outcome, together with the rarity of childhood cancer, will be a major challenge. However, with the advent of consortia such as the International Childhood Cancer Cohort Consortium, the availability of data and biological samples for such studies is becoming increasingly feasible.

And as we begin to understand what drives the increased risks of cancer in bigger babies, we may be able to move towards screening, and possibly even explore preventative measures.

Citation:

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

Int. J. Epidemiol. first published online January 27, 2015 doi:10.1093/ije/dyu265

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MedicalResearch.com Interview with:, & Kate A O’Neill (2015). Higher Birthweight Linked to Increased Childhood Cancer Risk MedicalResearch.com