Conclusions
The association of environmental factors and childhood cancer risk has been extensively studied, albeit yielding inconclusive so far results. Our exhaustive literature search on these factors and risk of 10 different childhood cancer types showed that only half of the reported associations reached a nominally statistical significance level, while only 2.4% of published meta-analyses were supported by highly suggestive evidence. Beyond any limitations and biases that may affect the summary effect estimates, the present findings, supported by mechanistic information, provide highly suggestive evidence that exposure to seven maternal/neonatal factors (including prenatal exposure to environmental chemicals or intake of B-vitamins) significantly affects -either increases or decreases- the risk of childhood leukemia, CNS tumors and testicular cancer. Considerable uncertainty remains for other stressors and outcomes. Further evidence from sufficiently powered studies and large consortia with uniform reporting of analyses is needed to allow firmer conclusions to be drawn. Given the increasing trend in the westernization of habits, evidence of the strength of the associations between lifestyle influences and childhood cancer may allow finer identification of people at high risk, who could be selected for individual-based primary prevention strategies.
Contributors : MK and EEN conceived and designed the study. MK, GM, CT, AK, XT and EEN acquired and collected the data. MK and GM analyzed the data. MK drafted the initial version of the manuscript. GM, CT, AK, XT, KT, LG, JS, A-BH, TS, AH, EP and EEN drafted and critically revised the manuscript for important intellectual content and gave final approval of the version to be published. EEN is the guarantor.
Acknowledgments/Funding: The present study is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ). None of the funders had any influence on the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. All authors had access to the data in the study and had final responsibility for the decision to submit for publication. Where authors are identified as personnel of the International Agency for Research on Cancer/ World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/ World Health Organization.
Competing Financial Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency : The lead author (MK) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.