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;

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.

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.

The epidemiological study conducted in this case by Santé publique France aims to identify one or more risk factors that are specific to children with cancer in this region and that are not found elsewhere or in a general sense.

This is a descriptive survey based on questionnaires administered to families with a sick child who are part of the cluster of cases. It first requires defining the scope of the study and then developing a detailed questionnaire to assess the families’ lifestyles. All of these questionnaires are analyzed by Santé publique France. If the results point to common local factors, the Agency may recommend environmental sampling.

A study population takes three factors into account: time, place, and person. The purpose of defining it is to maximize the “chance” of identifying one or more risk factors common to the cancers under study or to generate a hypothesis about a previously unknown risk factor. Thus, a scope that is too narrow prevents the inclusion of all relevant information, while a scope that is too broad risks diluting the quality of the information when attempting to establish a link between an exposure and the onset of the disease. Once established, the scope of a study cannot be changed, as doing so would skew the results.

In this case, the scope of the study includes:

• pediatric cancers of any type diagnosed between 2015 and 2019 in minors under the age of 18 at the time of diagnosis.

• The geographic area covers 7 municipalities: Sainte-Pazanne, Port-Saint-Père, Saint-Mars-de-Coutais, Machecoul-Saint-Même, Villeneuve-en-Retz, St-Hilaire-de-Chaléons, and the municipality of Rouans, which is near Sainte-Pazanne.

According to data validated by the Loire-Atlantique and Vendée Tumor Registry and the National Childhood Cancer Registry, as of October 10, 2019, this study involves 13 children with cancer, 3 of whom have since died.

As part of the epidemiological study, the questionnaire sent to the families involved will help describe the environment and lifestyle habits of children with cancer and identify potential overexposure to one or more risk factors mentioned in the scientific literature that may be common among these children.

It was developed based on current scientific knowledge. This questionnaire will collect information regarding:

• the child: details related to the diagnosis, the disease, and its management; family and personal medical history; information regarding primary and secondary residences and vacation destinations; the child’s childcare arrangements and schooling; leisure activities; dietary habits…

• the mother before, during pregnancy, and during breastfeeding (if applicable): personal medical history, environmental factors, medical factors, lifestyle habits…

• the father: personal medical history, environmental and medical factors, lifestyle habits prior to the child’s conception…

Defining the study area (time, place, and participants) requires a comprehensive search for all cancer cases within that area. To conduct the study with the scientific rigor that offers the best chance of identifying common factors that could explain the excess of pediatric cancers, the study area must remain fixed over time; otherwise, the results would be skewed.
The questionnaire is specific to the context of the geographic area selected for the epidemiological study.
Thus, the analysis of the questionnaire will be limited to the families included within the study’s scope.
Nevertheless, this document was also administered to 3 families outside the study area (2 outside the area due to age criteria but living in the sector, and 1 minor outside the geographic area). If a common exposure affecting the children is identified among them, the information could be sought in the 3 relevant questionnaires.

Santé publique France is conducting a study on the expectations and concerns of local stakeholders. This study complements the discussions taking place within the monitoring committee and the information provided by stakeholders through other channels. The study aims to gather the concerns, questions, expectations, insights, and actions of local stakeholders, as well as any differences in perspective, in order to provide tailored responses to local stakeholders.

This type of qualitative survey does not aim to achieve statistical representativeness of viewpoints but seeks, based on the number and selection of respondents, to capture the positions of the local stakeholders involved on various issues.

The survey was conducted through semi-structured face-to-face individual interviews or small group discussions (maximum of 5 people) with selected stakeholders, based on a questionnaire

About 20 interviews were conducted, involving 30 participants: leaders and members of local organizations and the “Stop Childhood Cancer” coalition, parents of children with cancer, local elected officials, school representatives, healthcare professionals, cancer surveillance experts, and residents of the affected towns.

The monitoring committee, which meets at the Pays de la Loire Regional Health Agency (ARS) in Nantes, brings together all stakeholders: professionals from the ARS, Santé publique France, and other relevant decentralized government agencies (Prefecture, Regional Directorate for the Environment, Planning, and Housing (DREAL)), local elected officials (mayors and members of parliament), school representatives (National Education, Uradel—private education), healthcare professionals (general practitioners, nurses, PMI, etc.), representatives of the “Stop Cancer in Our Children” collective, and a residents’ association.

This committee is chaired by Professor Jacques Dubin, an oncologist, maxillofacial surgeon, and ENT specialist. He has practiced at the Angers University Hospital, among other places. A former president of the Departmental Council of the Order of Physicians, he has participated in the regional ethics forum. He is also a member of the board of directors of the Maine-et-Loire Cancer League and a member of the user committee of the Regional Health and Autonomy Conference in the Pays de la Loire. His role as chair is to facilitate, in an impartial manner, dialogue among experts, health authorities, and stakeholders.

The monitoring committee was established to provide a forum for discussion and information-sharing with all stakeholders. It meets regularly to update stakeholders on the progress of the work, address any questions that may arise, and discuss proposals put forward by the various members.
The dates of the most recent meetings were May 21, June 26, and August 29.

In conjunction with the epidemiological investigation, environmental monitoring aimed at quickly “resolving uncertainties” regarding certain environmental exposures (identifying any instances where regulatory standards or guideline values were exceeded) and implementing protective measures if necessary was conducted by the ARS in collaboration with various operators. This verification was initially carried out at the Notre Dame de Lourdes School, located near a former industrial site, as several cases had attended this school. Investigations were conducted during the summer of 2019 in the vicinity of the industrial site and within the school. More than 150 samples were collected. The initial results were presented at the monitoring committee meeting on August 29, 2019, and to the school’s parents and teachers during a dedicated meeting in Ste Pazanne on September 11, 2019. They are published on the ARS Pays de la Loire website.
If, following the epidemiological investigation, other hypotheses related to a common environmental exposure emerge, further investigations may be proposed.

For more information: https://www.pays-de-la-loire.ars.sante.fr/investigations-sur-lexces-de-cas-de-cancers-pediatriques-sur-le-secteur-de-ste-pazanne