Pediatric Cancers in the Haut-Jura: Ongoing Epidemiological Research
The Bourgogne-Franche-Comté Regional Health Agency (ARS) was notified last July of an unusually high number of childhood cancer cases among residents of five municipalities in the Haut-Jura region (Les Rousses, Morbier, Morez, Saint-Pierre, and Prémanon).
Based on this report and after contacting the families, the agency compiled a list of ten affected children, in collaboration with the children’s primary care physicians and the Besançon University Hospital (CHRU), which provided support in confirming the diagnoses.
The children involved were between 6 months and 13 years old at the time of diagnosis.
On September 11, Santé publique France was notified by the Bourgogne-Franche-Comté Regional Health Agency (ARS) to conduct an epidemiological investigation into this report. The objective is to identify any known factors that might explain this cluster of sick children, in order to guide public health actions aimed at controlling it.
In the spirit of transparency and open communication, an informational meeting was held in mid-October with the families and in the presence of representatives from the ARS and Santé publique France. The purpose of the meeting was to discuss the approach, objectives, methodology, and the families’ involvement in this process, which is now underway.
The main stages of the investigation are:
to analyze the report and identify other children who may not have been reported;
to validate cancer diagnoses and link them to a specific time period and geographic area;
to compare the incidence of cancers observed over time and within the geographic area in question with statistics from the national childhood cancer registry;
to investigate potential environmental exposures and analyze the literature, i.e., the current state of scientific knowledge;
to conduct a multi-stage epidemiological investigation:
developing a dedicated and specific questionnaire focused on known or scientifically suspected risk factors for these cancers,
collecting information from families with their consent,
detailed analysis of the questionnaires,
summary and conclusions,
sharing the survey results with the families,
production of a report submitted to the ARS and made public.
Thus, the investigation should make it possible to:
rule out any “significant” risk factors that could be addressed locally (for example, shared exposure to risk in a place frequented by children, such as a daycare center);
address local questions and concerns, to the extent possible.
Q&A on pediatric cancers
Pediatric cancers
There are approximately 1,700 new cases of pediatric cancer in children under the age of 15 each year in mainland France.
The most common cancers are leukemias (28%), tumors of the central nervous system (24%), and lymphomas (11%).
Generally speaking, the causes of childhood cancers remain largely unknown today, and scientists primarily rely on genetic, immune-infectious, or environmental hypotheses. Based on current knowledge, the causes of pediatric cancers are most likely multifactorial.
Risk factors with a high level of evidence include:
medical ionizing radiation used for therapeutic purposes and radiation from atomic explosions, which are implicated in the development of several types of cancer;
genetic predispositions (predisposing diseases or genetic susceptibility) in acute lymphoblastic leukemia;
the Epstein-Barr virus (EBV) in Burkitt’s lymphoma.
Other factors are debated in the scientific literature, with a level of scientific evidence that remains insufficient to date to draw conclusions regarding causality. The main ones are described below:
individual factors: birth weight, use of assisted reproductive technology, as well as parental smoking and high consumption of certain foods (tea and coffee);
infectious factors: exposure to EBV and herpes viruses for leukemia;
Drug exposures: antiretrovirals, anticancer drugs, and oral contraceptives for several types of cancer;
exposure to environmental factors: Physical: high-voltage power lines (leukemia); ultraviolet radiation (acute lymphoblastic leukemia); Chemical: air pollution linked to road traffic, particularly benzene (leukemia); polychlorinated biphenyls (leukemia); solvents and hydrocarbons during the father’s occupational exposure; pesticides (blood disorders, central nervous system tumors, and even embryonic tumors), through domestic exposure or due to parents’ occupational exposure.
Population mixing, which corresponds to the immuno-infectious hypothesis, has also been cited in publications to explain increases in the incidence of childhood leukemia following population influx into a previously isolated area. Finally, certain authors also cite protective factors, such as breastfeeding; early exposure to infectious agents; and the quality of the mother’s or child’s diet in terms of fruits, vegetables, and vitamins;
Monitoring of pediatric cancers
This surveillance system was established, in particular, in the context of investigations into clusters of pediatric cancer cases: leukemias around La Hague at the inception of the Childhood Hematologic Diseases Registry (1990), and cancers at the Franklin-Roosevelt School in Vincennes at the inception of the Childhood Solid Tumors Registry (2000). These two registries have merged into a single entity (the National Registry of Childhood Cancers, or RNCE) and have provided robust and comprehensive data on the subject, addressing the questions raised. They also enable research to improve understanding of these cancers, as studies can now be conducted on larger sample sizes at the national level.
In France, the surveillance of childhood and adolescent cancers is carried out by the National Registry of Childhood Cancers (RNCE), which records all cases of cancer in children under the age of 15 in metropolitan France, dating back to 1990 for hematologic malignancies and to 2000 for solid tumors. Since 2011, it has been extended to residents of the Overseas Departments (Martinique, Guadeloupe, French Guiana, Réunion) and to adolescents under the age of 18.
A registry is defined as a continuous and comprehensive collection of personal data pertaining to one or more health events within a geographically defined population, maintained for the purposes of surveillance, research, or evaluation by a team with the appropriate expertise.
The registries:
contribute to health surveillance by producing national reference rates on incidence and survival, and by studying geographical and temporal variations in incidence.
monitor cancer incidence in populations considered “at risk”: children who have undergone specific treatments (antiretrovirals, radiation therapy, etc.). They contribute to the investigation of clusters of cancer cases reported in a geographic area.
also support cancer research conducted within the INSERM team on the epidemiology of childhood and adolescent cancers led by J. Clavel (EPICEA, CRESS, UMR-S1153). For example:
The GEOCAP program (GEOlocalized Study of Pediatric Cancers), whose objective is to study the role of environmental exposures in the occurrence of cancers in children under 15 years of age (road traffic and exposure to emitted pollutants, high-voltage power lines and electromagnetic fields, proximity to nuclear sites, natural ionizing radiation, UV radiation, etc.).
The ESCALE and ESTELLE studies, which examine the influence on childhood cancer risk of the course of pregnancy, the child’s characteristics at birth, the child’s environment in utero or during childhood (linked to the parents’ occupation or lifestyle), and genetic predispositions…
The MOBI-KIDS study investigates a link between exposure to radiofrequency radiation from cell phones and the occurrence of brain tumors in young people.
Cancer case clusters
A “spatio-temporal cluster” is a group of people with the same disease or symptoms within a specific geographic area and over a given period of time, where the number of cases relative to the population is unusually high.
Such a cluster may occur within a community due to various, and possibly interrelated, causes of genetic, environmental, infectious, occupational, or lifestyle origin. If no cause is identified, the role of chance cannot be ruled out, given the statistical distribution of cases over time and space and the possibility that the number of cases perceived as abnormal falls within this distribution and is simply an extreme outlier.
The identification of a cluster, however, raises the public health question of whether there is one (or more) common cause(s) that explains the clustering of disease cases over time and space.
As for the clusters reported to Santé publique France, they occur fairly frequently (several per year) and are systematically investigated based on the specific circumstances, with the assistance of the National Childhood Cancer Registry to identify confirmed cases.
Healthcare professionals have developed a specific protocol for investigating spatio-temporal clusters of disease cases, which is outlined in a methodological guide available on the Santé publique France website. This protocol calls for the collection of information on reported health issues and the environment in which they occurred.
The guiding scientific principle behind the investigation of a reported cluster is the notion that, if there is an “abnormal” clustering of people with the same disease, they should share exposure to one or more common causes, and that this exposure situation is not found in the rest of the population. Therefore, the epidemiological objectives of the response to a suspected cluster are to determine:
whether there is indeed an excess of cases in the observed population;
and, if such an excess exists, to determine whether there are one or more local causes for this cluster of cases, other than chance.
