The million children study on prenatal and childhood immunization and the risk of childhood cancer (CHIC)


Annually, there are around 1800 newly diagnosed cancers in children and adolescents under 15 years of age in Germany. Leukemia, lymphomas and tumors of the central nervous system are the most frequent malignancies in childhood. Malignant brain tumors and leukemia are among the ten leading causes of death in children and adolescents under age 15. The consequences of childhood cancer directly lead to a lower quality of life. Long-term effects of cancer therapy can also result in lifelong health restrictions (e.g. sterility). Less than 10% of the cases with the most common childhood cancers can be explained by specific genetic syndromes. To date, risk factors for most childhood cancers are largely unknown. For leukemia, the most common childhood cancer, ionizing radiation and specific chemical substances are the only established environmental carcinogenetic risk factors. Since affected children in most cases were not exposed to possible risk factors for a long time, a combination of several risk factors as well as prenatal factors is discussed as cause of childhood cancer. In addition, there are some protective factors under discussion. It is assumed that natural birth, long breastfeeding, absence of autoimmune diseases, early day-care attendance and infections as well as frequent vaccinations could prevent the development of childhood cancer over immunological pathways. However, findings of previous observational studies on the association between immunization by vaccination and development of childhood cancer are inconsistent.

Initially, the CHIC (The million children study on prenatal and childhood immunization and the risk of childhood cancer; principal investigator: Manuela Marron) project contains a systematic literature review to identify all previous studies dealing with this association and to combine the findings of those studies quantitatively in a meta-analysis for the first time. Based on pseudonymized health insurance data from the German Pharmacoepidemiological Research Database (GePaRD with 20 Mio. insured persons), a cohort of newborns will be created to examine the Germany-wide impact of immunization on the risk of childhood cancer. By linkage of mother-child pairs, not only immunizations of the children themselves but also immunizations of the mother during pregnancy are taken into account. This unique birth cohort will include more than 1 million children (17% of all German births) and will allow the observation of about 1300 cases of childhood cancer under the age of 15. The size of this birth cohort will facilitate detailed statistical analyses on different potential risk factors of childhood cancer and the consideration of numerous confounders (age, sex, socioeconomic status, vaccinations, inherited disorders, atopy, autoimmune diseases, infections, medications, medical examinations and therapies). Using this type of lifelong medical data from claims databases is highly valid. It can be analyzed in prevalence and incidence studies and potential recording errors by the study participants can be ruled out. In contrast to other countries, there is neither a compulsory vaccination program in Germany nor systematic registries for the administration of immunizations. Therefore initially, the vaccination prevalence will be investigated in this German birth cohort. Furthermore, the incidence of childhood cancer will be determined in this birth cohort and compared with available incidences from the German Childhood Cancer Registry. Subsequently, the association between immunization and the risk of childhood cancer will be analyzed throughout the lifespan. Detailed primary and secondary hypotheses for these analyses will be derived from the preceding meta-analysis.

The overall aim of this project is to identify immunological risk factors of specific childhood cancers. In the long term, a promising research approach arises out of this innovative study to examine further potential risk factors for childhood cancer using valid medical data from claims databases.

Funding period

Begin:   July 2016
End:   June 2017


  • BIPS funding (Institute's intramural fund)


Dr. phil. Manuela Marron