Registre National des Cancers de l’Enfant

Etude CADO-BIS CADO-BIS : High Resolution Study on the Diagnostic and Therapeutic Management of Adolescents and Young Adults (AYA, 15-24 years) diagnosed with Cancer
Investigator  Emmanuel Désandes, RNTSE, CHRU Nancy et INSERM UMRS 1153 - team EPICEA
Study period 2015-2017
Objectives To evaluate care pathways and quality of care for young adults (20-24 years) with cancer
Collaborations

Registre National des Tumeurs Solides de l’Enfant (RNTSE, B. Lacour)

Registre National des Hémopathies malignes de l’Enfant (RNHE, J. Clavel)

INSERM UMRS 1153-équipe EPICEA (J. Clavel)

General cancer registries of Calvados (AV Guizard), Doubs et Territoire de Belfort (AS Woronoff), Gironde (R. Salamon), l’Hérault (B. Trétarre), l’Isère (M. Colonna), Loire-Atlantique et Vendée (F. Molinié), la Manche (S. Bara), Lille et sa région (K. Jéhannin-Ligier), Bas-Rhin (M. Velten), Haut-Rhin (E. Marrer), la Somme (O. Ganry), Tarn (P. Grosclaude), Haute Vienne (A. Vergnenegre)

Specialised cancer registries: digestive cancers in Calvados (G. Launoy), haematological malignancies in Calvados (X. Troussard), CNS tumours in Gironde (I. Baldi), haematological malignancies Gironde (A. Monnereau)
Funding Ligue nationale contre le Cancer (Appel d’offres « Adolescents et Cancer ») 2013
Ligue nationale contre le Cancer (Appel d’offres « Adolescents et Cancer ») 2016
Statutory approvals CNIL DR-2014-412
Methods

The study focused on adolescents and young adults (AYA) aged 15 to 24 years, living in mainland France and diagnosed between 01 January 2012 and 31 December 2013, with a cancer (haematological or solid tumour), or a brain tumour whatever its grade.

Data collection was performed by cancer registries participating in the study: socio-demographic data (age, sex, location of residence, date of birth), clinical data (medical history, date of diagnosis, site, extension, histology), treatment data (protocol, clinical trial, treatment scheme), data on adolescent care pathways (at the time of diagnosis, of treatment and post-treatment follow-up) and follow-up data (relapse, vital status and date of last contact).

Results

The study included 993 AYA: 412 adolescents (15-19 years) and 581 young adults (20-24 years).

Management of adolescents (aged 15-19) diagnosed with cancer between 2012 and 2013 has improved compared to previous studies: CADO study (1988-1997, 10% of the French population) and EXECADO study (2006-2007, 41% of the French population).

The results highlight:

- an increase of the participation of paediatric oncologists (in paediatric care units or AYA units) in the treatment process for young people 15-17 years: 52.4% in 2012-2013 versus 51.1% in 2006-2007, and 16.5% in 1988-1997.- an increase of discussion of adolescent cancer at multidisciplinary team meetings (MTM): 85.9% in 2012-2013 versus 53.9% in 2006-2007- an increase of multidisciplinary team meetings involving at least one paediatric oncologist and one adult haemato-oncologist for adolescent patients: 22.9% in 2012-2013 versus 3.1% in 2006-2007.- an increase in enrolment of 15-19 years patients in randomized and non-randomized clinical trials: 39.5% in 2012-2013 versus 27.1% in 2006-2007, and  8.5% in 1988-1997. 

The CADO-BIS study is the first French study to describe care pathways and quality of care of young adults (20-24 years) with cancer. Compared to adolescents care management over the same period (2012-2013), recommendations for the young adults could:

- reduce the time to diagnosis, mainly for soft tissue sarcomas: 49 weeks (21-86) in young adults vs. 15 weeks (5-35) in adolescents (p = 0.02)- promote cancer care in AYA units: 10.0% for young adults vs. 20.6% for adolescents.- improve enrolment of young adults in randomized or non-randomized clinical trials: 16.8% of young adults vs. 39.5% of adolescents- enhance discussion at multidisciplinary team meetings (MTM) involving both paediatric and adult oncologists: 84.5% of which 88.4% in adult MTM, 10.5% mixed MTM, and 1% paediatric MTM.

 Publications  Desandes E, Brugieres L, Molinie F, Defossez G, Delafosse P, Jeahnnin-Ligier K, Velten M, Tretarre B, Amadeo B, Marrer E, Woronoff AS, Ganry O, Monnereau A, Preux PM, Troussard X, Daubisse-Marliac L, Bara S, Guizard AV, Baldi I, Launoy G, Clavel J, Lacour B. Adolescents and Young Adult Oncology Patients in France : heterogeneity in pathway in care. 
MOBI-EXPO MOBI-EXPO : Quantification of mobile phone exposure.
Investigators Martine Hours, Unité Epidémiologie et Surveillance Transport Travail Environnement (UMRESTTE) UMR T9405 - Lyon - for the French part
Study period 2012-2014
Objectives The main objective of the MOBI-EXPO international study is to characterize the use of mobile phones in young people and to validate the data on mobile phone use that are collected by questionnaire.
Collaborations 

Global Health Institute Barcelona (IS Global), Barcelona (E. Cardis),

Utrecht University (Netherlands),

Laboratoire de recherche en télécommunications (Whist Lab, France),

Institut français des sciences et technologies (IFSTARR, France),

Association pour la Recherche Epidémiologique dans les Cancers de l’Enfant et l’Adolescent (ARECEA),

Registre National des Tumeurs Solides de l’Enfant (RNTSE, B. Lacour), CHRU Nancy et INSERM UMRS 1153- team EPICEA
Funding Agence Nationale de Sécurité sanitaire de l’alimentation, de l’Environnement et du Travail
Statutory approvals CNIL DR-2010-303, DR-2012-490, avenant 1622882
Methods

MOBI-EXPO study involves researchers from 12 countries: Australia, Canada, France, Germany, Greece, Israel, Italy, Japan, the Netherlands, Korea, New Zealand, and Spain. Are included in each country 90 volunteers aged 10 and 24 years, who  use a mobile phone at least once a week.

Participants are selected within three age groups: 10-14, 15-19, and 20-24 years.

In France, they are selected in the same geographic areas as the cases and controls included in the MOBI-KIDS study: Alsace, Lorraine, Ile-de-France Petite-Couronne, Rhône-Isère, Hérault, Bouches-du-Rhône, and Gironde.

A special application was fitted on the volunteers’ personal phone, or on a rental mobile phone if the personal phone device was not compatible. It allowed to compare the mobile phone use estimated by the volunteer, collected by questionnaire, with its actual use recorded by the application (number and length of phone calls, laterality, number of sent texts etc.). The questionnaire answers were also compared to the records provided by the network operators, after the approval of the participants.

Results

534 volunteers participated in the study and completed the questionnaire six months after the use of the application, including 65 people in France.

The number and duration of calls was higher for girls than for boys, for those aged 20-24, and for the most deprived participants. These is great inaccuracy in the self-estimation of these indicators, with important variations between countries. Overall, participants tended to overestimate their total duration of use, and to underestimate their number of calls. Laterality and use of hands-free kits are also estimated with substantial imprecision.

Publications

Goedhart G, Vrijheid M, Wiart J, Hours M, Kromhout H, Cardis E, Eastman Langer C, de Llobet Viladoms P, Massardier-Pilonchery A, Vermeulen R. Using software-modified smartphones to validate self-reported mobile phone use in young people: A pilot study. Bioelectromagnetics. 2015 Oct;36(7):538-43

Langer C, de Llobet P, Dalmau A, Wiart J, Goedhart G, Hours M, Benke G, Bouka E, Bruchim R, Choi KH, Eng A, Ha M, Karalexi M, Kiyohara  K, Kojimahara  N, Krewski D, Kromhout H, Lacour B, Mannetje A, Maule M, Migliore E, Mohipp C, Momoli F, Petridou E, Radon K, Remen T, Sadetzki S, Sim M, Weinmann T, Vermeulen R, Cardis E, Vrijheid M. Patterns of cellular phone use among young people in 12 countries: Implications for RF exposure. Environ Int, 2017, 107 : 65-74

Goedhart G, van Wel L, Langer CE, et al. Recall of mobile phone usage and laterality in young people: the multinational Mobi-Expo study. 2018 Aug;165:150-157.

ESCALE STUDY

ESCALE - Case-control study on childhood cancers (leukaemias, lymphomas, brain tumours, neuroblastomas).

Investigator Jacqueline Clavel -  INSERM UMRS 1153 – team EPICEA
Period 2003-2004
Objectives

- To analyse the association between the risk of childhood cancers and the events of pregnancy, the child’s characteristics at birth, the environment in foetal period and early childhood, exposures related to the parents’ occupation or lifestyle, or related to the home location , a family history of cancer, congenital malformations, or autoimmune diseases.

- To identify genetic factors that may modulate the role of these factors, including polymorphisms in genes involved in xenobiotic transport and metabolism, DNA repair, immune response, or foetal growth and cell differentiation.

- To analyse the interactions between all these polymorphisms and environmental factors.

Collaborations

SFCE, Services d’hémato-oncologie et de neurochirurgie pédiatriques,

Institut CSA, CRB Epigenetec (INSERM U775), CNG, Géocible, Integragen

Funding Fondation de France, ARC, AFSSAPS, Cent pour Sang la Vie, Inserm, AFSSET, ANR, INCA
Statutory approval CNIL (902162) – RBM (DGS 2003/0259)
Methods

The ESCALE study was conducted in 2003-2004 all over mainland France. The study included :

-        1,466 cases diagnosed with leukaemia (764), or Hodgkin lymphoma (130), non-Hodgkin lymphoma (166), invasive brain tumour (209) or neuroblastoma (197) before age 15 years.

-        1,681 controls of the same age and of the same sex, on average, as the cases, selected by frequency-matching in the general population. 

The biological mothers of cases and controls were interviewed by phone, in a standardised way, and asked about the child’s individual and familial medical history and environment.

A biological sampling was performed subject to the informed consent of the parents. It consisted of a blood sample (for cases) or saliva sample (controls, case parents, and relatives if there was a specific medical family history).

Publications

Childhood leukaemia

- Maternal and birth characteristics, vaccinations

Mallol-Mesnard N, Menegaux F, Auvrignon A, Auclerc MF, Bertrand Y, Nelken B, Robert A, Michel G, Margueritte G, Perel Y, Méchinaud F, Bordigoni P, Leverger G, Baruchel A, Hémon D, Clavel J. Vaccination and the risk of childhood acute leukaemia: The ESCALE study (SFCE). Int J Epidemiol 2007;36(1):110-6.

Amigou A, Rudant J, Orsi L, Goujon-Bellec S, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel G, Haouy S, Chastagner P, Ducassou S, Rialland X, Hémon D, Clavel J. Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: The ESCALE study (SFCE). Cancer Causes Control 2012;23(8):1265-77.

Rudant J, Amigou A, Orsi L, Althaus T, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel G, Sirvent N, Chastagner P, Ducassou S, Rialland X, Hémon D, Clavel J. Fertility treatments, congenital malformations, fetal loss, and childhood acute leukemia: The ESCALE study (SFCE). Pediatr Blood Cancer 2013;60(2):301-8.

- Maternal use of tobacco, alcohol, and coffee during pregnancy

Rudant J, Menegaux F, Leverger G, Baruchel A, Lambilliotte A, Bertrand Y, Patte C, Pacquement H, Vérité C, Robert A, Michel G, Margueritte G, Gandemer V, Hémon D, Clavel J. Childhood hematopoietic malignancies and parental use of tobacco and alcohol: The ESCALE study (SFCE). Cancer Causes Control 2008;19(10):1277-90.

Bonaventure A, Goujon-Bellec S, Rudant J, Orsi L, Leverger G, Baruchel A, Bertrand Y, Nelken B, Pasquet M, Michel G, Sirvent N, Bordigoni P, Ducassou S, Rialland X, Zelenika D, Hémon D, Clavel J. Maternal smoking during pregnancy, genetic polymorphisms of metabolic enzymes, and childhood acute leukemia: The ESCALE study (SFCE). Cancer Causes Control 2012;23(2):329-45.

Bonaventure A, Rudant J, Goujon-Bellec S, Orsi L, Leverger G, Baruchel A, Bertrand Y, Nelken B, Pasquet M, Michel G, Sirvent N, Bordigoni P, Ducassou S, Rialland X, Zelenika D, Hémon D, Clavel J. Childhood acute leukemia, maternal beverage intake during pregnancy, and metabolic polymorphisms. Cancer Causes Control 2013 :24(4):783-93.

- Early stimulation of the immune system, breastfeeding, early common infections, and allergy

Rudant J, Orsi L, Menegaux F, Petit A, Baruchel A, Bertrand Y, Lambilliotte A, Robert A, Michel G, Margueritte G, Tandonnet J, Mechinaud F, Bordigoni P, Hémon D, Clavel J. Childhood acute leukemia, early common infections, and allergy: The ESCALE study. Am J Epidemiol 2010;172(9):1015-27.

- Other environmental exposures

Rudant J, Menegaux F, Leverger G, Baruchel A, Nelken B, Bertrand Y, Patte C, Pacquement H, Vérité C, Robert A, Michel G, Margueritte G, Gandemer V, Hémon D, Clavel J. Household exposure to pesticides and risk of childhood hematopoietic malignancies: The ESCALE study (SFCE). Environ Health Perspect 2007;115(12):1787-93.

Brosselin P, Rudant J, Orsi L, Leverger G, Baruchel A, Bertrand Y, Nelken B, Robert A, Michel G, Margueritte G, Perel Y, Mechinaud F, Bordigoni P, Hémon D, Clavel J. Acute childhood leukaemia and residence next to petrol stations and automotive repair garages: The ESCALE study (SFCE). Occup Environ Med 2009;66(9):598-606.

Amigou A, Sermage-Faure C, Orsi L, Leverger G, Baruchel A, Bertrand Y, Nelken B, Robert A, Michel G, Margueritte G, Perel Y, Mechinaud F, Bordigoni P, Hémon D, Clavel J. Road traffic and childhood leukemia: The ESCALE study (SFCE). Environ Health Perspect 2011;119(4):566-72

- Family history of cancer and genetic factors

Rudant J, Menegaux F, Leverger G, Baruchel A, Nelken B, Bertrand Y, Hartmann O, Pacquement H, Vérité C, Robert A, Michel G, Margueritte G, Gandemer V, Hémon D, Clavel J. Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-hodgkin's lymphoma: The ESCALE study (SFCE). Int J Cancer 2007;121(1):119-26.

Orsi L, Rudant J, Bonaventure A, Goujon-Bellec S, Corda E, Evans TJ, Petit A, Bertrand Y, Nelken B, Robert A, Michel G, Sirvent N, Chastagner P, Ducassou S, Rialland X, Hémon D, Milne E, Scott RJ, Baruchel A, Clavel J. Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE). Leukemia 2012;26(12):2561-4.

Rudant J, Orsi L, Bonaventure A, Goujon-Bellec S, Corda E, Baruchel A, Bertrand Y, Nelken B, Robert A, Michel G, Sirvent N, Chastagner P, Ducassou S, Rialland X, Hémon D, Leverger G, Clavel J. Are ARID5B and IKZF1 polymorphisms also associated with childhood acute myeloblastic leukemia: The ESCALE study (SFCE)? Leukemia 2013 ;27(3):746-8.

Rudant J, Orsi L, Bonaventure A, Goujon-Bellec S, Baruchel A, Petit A, Bertrand Y, Nelken B, Pasquet M, Michel G, Saumet L, Chastagner P, Ducassou S, Réguerre Y, Hémon D, Clavel J. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: The ESCALE study. PLoS ONE. 10(3):e0121348.  (2015b)

- Other cancers

Mallol-Mesnard N, Menegaux F, Lacour B, Hartmann O, Frappaz D, Doz F, Bertozzi AI, Chastagner P, Hémon D, Clavel J. Birth characteristics and childhood malignant central nervous sytem tumors: The ESCALE study (French society for childhood cancer). Cancer Detect Prev 2008;32(1):79-86.

Plichart M, Menegaux F, Lacour B, Hartmann O, Frappaz D, Doz F, Bertozzi AI, Defaschelles AS, Pierre-Kahn A, Icher C, Chastagner P, Plantaz D, Rialland X, Hémon D, Clavel J. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: The ESCALE study (SFCE). Eur J Cancer Prev 2008;17(4):376-83.

Munzer C, Menegaux F, Lacour B, Valteau-Couanet D, Michon J, Coze C, Bergeron C, Auvrignon A, Bernard F, Thomas C, Vannier JP, Kanold J, Rubie H, Hémon D, Clavel J. Birth-related characteristics, congenital malformation, maternal reproductive history and neuroblastoma: The ESCALE study (SFCE). Int J Cancer 2008;122(10):2315-21.

Rudant J, Orsi L, Monnereau A, Patte C, Pacquement H, Landman-Parker J, Bergeron C, Robert A, Michel G, Lambilliotte A, Aladjidi N, Gandemer V, Lutz P, Margueritte G, Plantaz D, Méchinaud F, Hémon D, Clavel J. Childhood Hodgkin's lymphoma, non-hodgkin's lymphoma and factors related to the immune system: The escale study (SFCE). Int J Cancer 2011;129(9):2236-47.

Rios P, Bailey HD, Orsi L, Lacour B, Valteau-Couanet D, Levy D, Corradini N, Leverger G, Defachelles AS, Gambart M, Sirvent N, Thebaud E, Ducassou S, Clavel J. Risk of neuroblastoma, birth-related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE).  Int J Cancer. 139(9):1936-48. (2016)

Rios P, Bailey HD, Lacour B, Valteau-Couanet D, Michon J, Bergeron C, Boutroux H, Defachelles AS, Gambart M, Sirvent N, Thebaud E, Ducassou S, Orsi L, Clavel J. Maternal use of household pesticides during pregnancy and risk of neuroblastoma in offspring. A pooled analysis of the ESTELLE and ESCALE French studies (SFCE). Cancer Causes Control. Epub ahead of print 10.1007/s10552-017-0944-5  (2017)

Bailey HD, Lacour B, Guerrini-Rousseau L, Bertozzi A, Leblond P, Faure-Conter C, Pellier I, Freycon C, Doz F, Puget S, Ducassou S, Orsi L, Clavel J. Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France). Cancer Causes Control. 28(7):719-32 (2017)

Bailey HD, Rios P, Lacour B, Guerrini-Rousseau L, Bertozzi AI, Leblond P, Faure-Conter C, Pellier I, Freycon C, Michon J, Puget S, Ducassou S, Orsi L, Clavel J. Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France). Int J Cancer. 140(8):1757-69. (2017)

PhDs

Jérémie Rudant, « Facteurs de risque environnementaux et familiaux des hémopathies malignes de l'enfant » (dir. J. Clavel), Université Paris-Sud, defended in 2009

Alicia Amigou, « Etude des facteurs de risque des leucémies de l'enfant » (dir. J. Clavel), Université Paris-Sud,  defended in 2013

Audrey Bonaventure, « Facteurs de risque des leucémies de l'enfant » (dir. J. Clavel), Université Paris-Sud,  defended in 2014

Roula Ajrouche, « Facteurs de risque des leucémies de l'enfant » (dir. J. Rudant et J. Clavel), Université Paris-Sud,  defended in 2015

Astrid Coste, « Rôle des expositions environnementales aux rayons ultraviolets naturels et aux pesticides liés aux activités agricoles et hémopathies malignes de l’enfant » (dir. J. Clavel), Université Paris-Descartes,   defended in 2017

Paula Rios, «Facteurs de risque environnementaux et périnataux des neuroblastomes de l'enfant » (dir. J. Clavel), Université Paris-Descartes,  defended in 2019

Nicolas Vidart, «Facteurs de risque environnementaux des tumeurs cérébrales de l'enfant » (dir. J. Clavel), Université Paris-Descartes,  defended in 2019

Consortium

CLIC – Childhood Leukemia International Consortium

Investigators

Jacqueline Clavel, Stéphanie Goujon-Bellec, Denis Hémon, Laurent Orsi, Jérémie Rudant - INSERM UMRS 1153 - team EPICEA

Objectives To analyse the risk factors for childhood leukaemia
Collaborations http://circle.berkeley.edu/research/childhood-leukemia-international-consortium/
 Methods

An article sets out the methods:

Metayer C, Milne E, Clavel J, Infante-Rivard C, Petridou E, Taylor M, Schüz J, Spector LG, Dockerty JD, Magnani C, Pombo-de-Oliveira MS, Sinnett D, Murphy M, Roman E, Monge P, Ezzat S, Mueller BA, Scheurer ME, Armstrong BK, Birch J, Kaatsch P, Koifman S, Lightfoot T, Bhatti P, Bondy ML, Rudant J, O'Neill K, Miligi L, Dessypris N, Kang AY, Buffler PA. The childhood leukemia international consortium. Cancer Epidemiol 2013:37(3):336-47.

The EPICEA team contributes to the CLIC with data from the ESCALE and ESTELLE studies, and with two older studies: ADELE and ELECTRE.

Publications

Marcotte EL, Thomopoulos TP, Infante-Rivard C, Clavel J, Petridou ET, Schüz J, Ezzat S, Dockerty JD, Metayer C, Magnani C, Scheurer ME, Mueller BA, Mora AM, Wesseling C, Skalkidou A, Rashed WM, Francis SS, Ajrouche R, Erdmann F, Orsi L, Spector LG.  Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).  Lancet Haematol. 2016; 3(4):e176-85. 

Metayer C, Milne E, Dockerty JD, Clavel J, Pombo-de-Oliveira MS, Wesseling C, Spector LG, Schuz J, Petridou E, Ezzat S, Armstrong BK, Rudant J, Koifman S, Kaatsch P, Moschovi M, Rashed W, Selvin S, McCauley K, Kang AY, Hung RJ, Buffler PA, Infante-Rivard C. Maternal supplementation with folic acid and other vitamins before and during pregnancy and risk of leukemia in the offspring: A childhood leukemia international consortium (CLIC) study. Epidemiology. 2013; 73(8). 

Bailey H, Fritschi L, Infante-Rivard C, Glass DC, Miligi L, Dockerty JD, Lightfoot T, Clavel J, Roman E, Spector LG, Kaatsch P, Metayer C, Magnani C, Milne E, Polychronopoulou S, Simpson J, Rudant J, Sidi V, Rondelli R, Orsi L, Kang A, Petridou E, Schuz J. Parental occupational pesticide exposure and the risk of chilhdood leukemia in the offspring: findings from the Childhood Leukemia International Consortium. Int. J. Cancer. 2014;135(9):2157-72). 

Zhang L, Samad A, Pombo-de-Oliveira MS, Scelo G, Smith MT, Feusner J, Wiemels JL, Metayer C. Global characteristics of childhood acute promyelocytic leukemia. Blood Rev. 2014; 29(2):101-25.

Milne E, Greenop KR, Metayer C, Schuz J, Petridou E, Pombo-de-Oliveira MS, Infante-Rivard C, Roman E, Dockerty JD, Spector LG, Koifman S, Orsi L, Rudant J, Dessypris N, Simpson J, Lightfoot T, Kaatsch P, Baka M, Faro A, Armstrong BK, Clavel J, Buffler PA. Fetal growth and childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium (CLIC). Int. J. Cancer. 2013; 133(12):2968-2979.

Bailey H, Fritschi L, Metayer C, Infante-Rivard C, Magnani C, Petridou E, Roman E, Spector LG, Kaatsch P, Clavel J, Milne E, Dockerty JD, Glass DC, Lightfoot T, Miligi L, Rudant J, Baka M, Rondelli R, Amigou A, Simpson J, Kang AY, Moschovi M. Parental occupational paint exposure and risk of childhood leukemia in the offspring: Findings from the Childhood Leukemia International Consortium. Cancer Causes Control. 2014; 25(10):1351-1367.

Rudant J, Lightfoot T, Urayama K, Petridou E, Dockerty J, Magnani C, Milne E, Spector L, Ashton L, Dessypris N, Kang A, Miller M, Rondelli R, Simpson J, Stiakaki E, Orsi L, Roman E, Metayer C, Infante-Rivard C, Clavel J. Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium (CLIC) Study. Am. J. Epidemiol. 2014; 181(8):549-62.

Bailey HD, Metayer C, Milne E, Petridou E, Infante-Rivard C, Spector LG, Clavel J, Dockerty JD, Zhang L, Armstrong BK, Rudant J, Fritschi L, Amigou A, Chatzipadelis E, Kang AY, Stiakaki E, Joachim Schüz. Home paint exposures and risk of childhood acute lymphoblastic leukemia: Findings from the Childhood Leukemia International Consortium. Cancer Causes Control; 2015 26(9):1257-70.
MOBI-KIDS France

Communication technologies, environment and brain tumours in young people.

Investigators Brigitte Lacour, RNTSE CHRU Nancy et INSERM UMRS 1153 - team EPICEA
Study period 2009-2015
Objectives

MOBI-KIDS is an international study aiming to assess the potential carcinogenic effects on the central nervous system of childhood and adolescent exposure to radio frequency from mobile phones and other sources

Collaborations 

Global Health Institute Barcelona (IS Global), Barcelone (E. Cardis)

UMRESTTE, UMRT 9405, Lyon (M. Hours)

ARECEA (Association pour la Recherche Epidémiologique dans les Cancers de l’Enfant et l’Adolescent)

Registre National des Tumeurs Solides de l’Enfant (RNTSE, B. Lacour)

Funding

Commission Européenne (7th Framework Programme)

Fondation Santé et Radiofréquences (Appel à Projets 2008)

Fondation Pfizer (Appel à Projets 2011)

Agence Nationale de Sécurité sanitaire de l’alimentation, de l’Environnement et du Travail (APREST 2013 « Radiofréquences »)

INCa (subvention hors appel à projets 2013)

Ligue nationale contre le cancer (Appel d’offres « Adolescents et cancer » 2013).

Statutory approval CNIL DR-2010-303 et DR-2012-490
Methods

Mobi-Kids is prospective international epidemiological case-control study, conducted in 14 countries: Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, the Netherlands, Korea, New Zealand, and Spain.

The exposure to radiofrequency  generated by mobile phones is compared in two populations among young people aged 10 to 24 years:

- Cases, who have a confirmed diagnosis of primary brain tumours, whether malignant or benign

- Controls, who are selected from among young people who had surgery for acute appendicitis, and matched to cases on age, sex and department of residence.

In France, the study was conducted in 16 departments covering 7 regions: Alsace, Lorraine, Ile-de-France Petite-Couronne, Rhône-Isère, Hérault, Bouches-du-Rhône, and Gironde.

Cases were recruited from March 2011 to December 2014. Data were collected by a face-to-face interview, about information on socio-demographic factors, complete residential history, and exposure to other environmental factors, including mobile phone use. Data collection and interviewing cases and controls were performed until April 2015.

At the same time, data validation studies were conducted: accurate mapping of the brain tumours using a specific software (Gridmaster), validation of histological diagnoses on a sub-sample of cases (20%) and validation. Data reported by the cases and the controls on the duration of exposure to mobile phones were cross-checked with network operators.

Results

At the international level, in March 2016, a total of 901 cases and 1922 controls were included. France ranks third among the participating countries with over 10% of all participants: 104 cases and 188 controls included. This represents a ratio of 1.8 controls per case, close to the expected 2 controls per case.

International analyses are ongoing, taking into account the results of validation studies and non-responding questionnaires.

Two types of analysis are carried out: analyses on the association between brain tumours and mobile phone use characteristics (duration of use in years, length of calls, and number of calls), and analyses according to the exposure to extremely low frequency (ELF) electromagnetic fields (EMF) and radiofrequency (RF) at the location of the tumour.

Specific work has been performed to estimate the exposure, taking account of the technical factors related to the phone itself, to the communication system used, and  to how the phone is used. Algorithms have been developed to evaluate the SAR (Specific Absorption Rate) at the tumour location for radiofrequencies and for ELF electromagnetic fields. An algorithm to estimate exposure due to devices in the general environment has also been developed.

Full results will be disseminated after international publications.

Some descriptive data are available :PopulationAt the international level, 901 cases and 1922 controls were included: 103 cases and 188 controls in the French study. Cases were aged 16.3 years on average, and control 16.0 years in France, which is very similar to those in the international study (16.5 and 16.6 years respectively). 

Tumour cases

The distribution by tumour site shows a slightly higher frequency of cerebellar and brain stem tumours in France (25.6% and 12.0, % versus 21.3% and 8.7% respectively for all countries), with a higher proportion of median tumours (34% vs. 23%). There is a very slight predominance of tumours on the left side in the French study as well as for all cases.

Exposure

The vast majority of young people are regular users of the mobile phone: 85.5% in France, and 84.2% for all countries.

The average number of calls made per day was 1.6 at the beginning of mobile use, and is 3.7 for the most recent use. The daily communication time increases from 5.4 minutes per day at the beginning of mobile use, to 17.7 minutes per day for the recent data. However, it still necessary to adjust these indicators of mobile phone use in the analyses, because validation studies such as Mobi-Expo showed that users tend to underestimate the number of calls but to overestimate their duration.

WIFI is another source of exposure to RF, mostly at home (91% of cases), more rarely at school (25%) or in other places (17%).

Exposures to other low-frequency electromagnetic fields include the cell phone charger (45%), hairdryer or hair straightener (42%), radio alarm clock (31%), induction cooker (17%), TV (16%) and more rarely, the cordless-phone dock (7%).

Publications 

Dedicated website: : http://www.mbkds.com

Lacour B, Delmas D, pour l’équipe Mobi-Kids France. Etude MOBI-KIDS « Technologies de communication, Environnement et Tumeurs Cérébrales chez les jeunes ». Profession Cancérologue, 2010, 21(1) :26.

Rémen T, Delmas D, Hours M, Lacour B. Etude MOBI-KIDS : Technologies de communication, expositions environnementales et tumeurs cérébrales chez les jeunes [MOBI-KIDS study : Communication technology, environment and brain tumours in young people]. Revue d'Oncologie Hématologie Pédiatrique, 2014, 2 :4-29.

Sadetzki S, Eastman Langer C, Bruchim R, Kundi M, Merletti F, Vermeulen R, Kromhout H, Lee AK, Maslanyj M, Sim M, Taki M, Wiart J, Armstrong B, Milne E, Benke G, Schattner R, Hutter HP, Woehrer A, Krewski D, Mohipp C, Momoli F, Ritvo P, Spinelli J, Lacour B, Delmas D, Remen T, Radon K, Weinmann T, Klostermann S, Heinrich S, Petridou E, Bouka E, Panagopoulou P, Dikshit R, Nagrani R, Even-Nir H, Chetrit A, Maule M, Migliore E, Filippini G, Miligi L, Mattioli S, Yamaguchi N, Kojimahara N, Ha M, Choi KH, Mannetje A, Eng A, Woodward A, Carretero G, Alguacil J, Aragones N, Morales Suare-Varela M, Goedhart G, Schouten-van Meeteren AY, Reedijk AM, Cardis E. The MOBI-Kids study protocol: Challenges in assessing childhood and adolescent exposure to electromagnetic fields from wireless telecommunication technologies and possible association with brain tumor risk. Front Public Health, 2014, 2 : article 124.

Calderon C, Ichikawa H, Taki M, Wake K, Addison D, Mee T, Maslanyj M, Kromhout H, Lee AK, Sim MR, Wiart J, Cardis E. ELF exposure from mobile and cordless phones for the epidemiological MOBI-Kids study. Environ Int. 2017 Apr;101:59-69. doi: 10.1016/j.envint.2017.01.005.

Turner MC, Gracia-Lavedan E, Momoli F, Langer CE, Castano-Vinyals G,  Kundi M, Maule M, Merletti F, Sadetzki S, Vermeulen R, Albert A, Alguacil J, Aragones N, Badia F, Bruhim R, Carretero G, Kojimahara N, Lacour B, Morales-Suarez-Varela M, Radon K, Remen T, Weinmann T, Yamaguchi N, Cardis E. Nonparticipation Selection Bias in the MOBI-KIDS Study. Epidemiology, 2019 Jan; 30(1): 145–153.

GEOCAP STUDY

GEOCAP - Case-control study based on childhood cancer geolocation

Investigator Jacqueline Clavel, Denis Hémon -  INSERM UMRS 1153 – team EPICEA
Period 2002-…
Objectives

Primary objective: To study the influence of several environmental exposures on the risk of childhood cancer

- proximity to power lines, and exposure to electric and extremely low frequency-magnetic fields

- proximity to traffic lanes, and environmental exposure to benzene and other pollutants

- exposure of home location to natural ionising radiation, especially radon and gamma radiation

- proximity to nuclear power plants

- proximity to agricultural crops

- socio-economic level of the IRIS of the residence

Secondary objective :

To estimate the exposure of the general population under 15 to these factors.

 

Collaborations

INSEE, Geocible, IGN

IRSN/DRPH/SER, IRSN/DRPH/SRBE, IRSN/PRP-DGE/SEDRAN/BRN, RTE, InVS/DSE, AIRPARIF, ADEME

Funding

EDF, Fondation Pfizer, Institut national de Veille Sanitaire (InVS), Agence Nationale de la Recherche (ANR) -Investissement d’Avenir HOPE-EPI, Agence nationale de sécurité sanitaire de l’alimentation (ANSES), Fondation ARC pour la recherche sur le cancer, Institut National Du Cancer (INCa), Cancéropôle d’île de France

Statutory approval  CNIL Registre National des Hémopathies malignes de l’Enfant (n°998198) et Registre National des Tumeurs Solides de l’Enfant (n°900183)
Methods

- Case recruitment: all cancer cases in children aged less than 15 years, who have been diagnosed with cancer or benign brain tumour since 2002, living in mainland France at the time of diagnosis.

- Control recruitment: sample of 5000 child addresses per year, created by INSEE on tax record database, representative of all children less than 15 years living in mainland France.

- Geolocation of addresses anonymously and blinded to the case-control status (Geocible, bases Navteq et IGN).

- Modelling of radiation doses due to gas release from nuclear power plants: IRSN/DRPH/SER ; Data on natural ionizing radiation sources: IRSN/PRP-DGE/

SEDRAN/BRN ; Power lines location: RTE

Results

The first analysis concerned the leukaemia risk in the vicinity of French nuclear power plants, and was carried out in collaboration with IRSN.

We observed a higher risk of leukaemia in children living less than 5 km from a nuclear power plant over the period 2002-2007, but this leukaemia risk appeared to be independent of the estimated radioactive exposure by modelling gas releases.

Publications

Sermage-Faure C, Laurier D, Goujon-Bellec S, Chartier M, Guyot-Goubin A, Rudant J, HémonD, Clavel J. Childhood leukemia around French nuclear power plants--the geocap study, 2002-2007. Int J Cancer 2012;131(5):E769-80.

Clavel J, Sermage-Faure C, Goujon-Bellec S, Rudant J, Guyot-Goubin A, Chartier M, Laurier D, Hémon D. Childhood leukemia around French nuclear power plants - the geocap study, 2002-2007 - responses to letters. Int J Cancer 2012. Letter

Sermage-Faure C, Demoury C, Rudant J, Goujon-Bellec S, Guyot-Goubin A, Deschamps F,Hemon D, Clavel J. Childhood leukemia close to high voltage power lines – the Geocap study, 2002-2007. Br J Cancer, 2013;108(9):1899-906.

Houot J, Marquant F, Goujon S, Faure L, Honoré C, Roth MH, Hémon D, Clavel J. Residential proximity to heavy-traffic roads, benzene exposure, and childhood leukemia-the GEOCAP study, 2002-2007. Am J Epidemiol. 182(8):685-93. (2015)

Marquant F, Goujon S, Faure L, Guissou S, Orsi L, Hémon D, Lacour B, Clavel J. Risk of childhood cancer and socio-economic disparities: Results of the French nationwide study geocap 2002-2010. Paediatr Perinat Epidemiol. 30(6):612-22. (2016)

PhDs

Claire Sermage-Faure « Incidence des leucémies de l'enfant en fonction de la proximité et des caractéristiques générales de diverses sources d'expositions environnementales » (dir. D. Hémon), Université Paris-Sud, defended in 2012

Claire Demoury « Rôle des expositions résidentielles au radon et aux champs électriques et magnétiques à extrêmement basse fréquence dans l'incidence des leucémies de l'enfant » (dir.. D. Hémon), Université Paris-Sud, defended in 2014

Jennifer Houot « Facteurs de risque environnementaux des leucémies de l'enfant » (dir. D. Hémon), Université Paris-Sud, defended in 2016

Astrid Coste, « Rôle des expositions environnementales aux rayons ultraviolets naturels et aux pesticides liés aux activités agricoles et hémopathies malignes de l’enfant » (dir. J. Clavel), Université Paris-Descartes,  defended in 2017

ESTELLE STUDY

ESTELLE - Case-control study on childhood cancers (leukaemias, lymphomas, brain tumours, neuroblastomas, nephroblastomas, hepatoblastomas).

Investigators Jacqueline Clavel, Jérémie Rudant- INSERM UMRS 1153 – team EPICEA
Period 2010-2011
Objectives

- To analyse the association between the risk of childhood cancers and the events of pregnancy, the child’s characteristics at birth, the environment in foetal period and early childhood, exposures related to the parents’ occupation or lifestyle, or related to the home location, a family history of cancer, congenital malformations, or autoimmune diseases.

 - To identify genetic factors that may modulate the role of these factors, including polymorphisms in genes involved in xenobiotic transport and metabolism, DNA repair, immune response, or foetal growth and cell differentiation.- To analyse the interactions between all these polymorphisms and environmental factors.

Collaborations

SFCE, Services d’hémato-oncologie et de neurochirurgie pédiatriques,
CRB Epigenetec (INSERM U775), IPSOS, Geocible, Integragen
Caroline Besson (Inserm U802), Judith Landman-Parker (Hôpital Trousseau), Isabelle Janoueix (Inserm U830)

Funding INCa, Ligue Nationale contre le Cancer, Enfants et Santé, DHOS
Statutory approval CNIL (908283) – avis favorable CPP Ile de France IV, 2008/12NICB (hors RBM)
Methods

ESTELLE study was conducted in 2010-2011 all over mainland France, following to the methods of the previous study ESCALE.

The study  included :

-        1,814 cases diagnosed with either leukaemia (740), Hodgkin lymphoma (206), non-Hodgkin lymphoma (174), brain tumour (339), neuroblastoma (201), nephroblastoma (134), or hepatoblastoma (22) before the age of 15 years.

-        1,423 controls of the same age and of the same sex, on average, as the cases, selected by frequency-matching in the general population.

The biological mothers of cases and controls were interviewed by phone, in a standardised way, and asked about the child’s individual and familial medical history and  environment.

A biological sampling was performed subject to the informed consent of the parents. It consisted of a blood (for cases) or saliva sample (controls, case parents, and relatives if there was a specific medical family history).

Results

Analyses are ongoing. For some cancer types, the ESTELLE data will be analysed together with the data from the previous study ESCALE.

Publications

Ajrouche R, Rudant J, Orsi L, Petit A, Baruchel A, Nelken B, Pasquet M, Michel G, Bergeron C, Ducassou S, Gandemer V, Lutz P, Saumet L, Rialland X, Hémon D, Clavel J. Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood acute leukemia: The ESTELLE study. Cancer Causes Control. 25(10):1283-93. (2014)

Ajrouche R, Rudant J, Orsi L, Petit A, Baruchel A, Lambilliotte A, Gambart M, Michel G, Bertrand Y, Ducassou S, Gandemer V, Paillard C, Saumet L, Blin N, Hémon D, Clavel J. Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: The estelle study (SFCE). Br J Cancer. 112(6):1017-26. (2015)

Orsi L, Rudant J, Ajrouche R, Leverger G, Baruchel A, Nelken B, Pasquet M, Michel G, Bertrand Y, Ducassou S, Gandemer V, Lutz P, Saumet L, Moreau P, Hemon D, Clavel J. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: The ESTELLE study. Cancer Causes Control. 26(7):1003-17. (2015)

Rios P, Bailey HD, Orsi L, Lacour B, Valteau-Couanet D, Levy D, Corradini N, Leverger G, Defachelles AS, Gambart M, Sirvent N, Thebaud E, Ducassou S, Clavel J. Risk of neuroblastoma, birth-related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE). Int J Cancer. 139(9):1936-48. (2016)

Rios P, Bailey HD, Lacour B, Valteau-Couanet D, Michon J, Bergeron C, Boutroux H, Defachelles AS, Gambart M, Sirvent N, Thebaud E, Ducassou S, Orsi L, Clavel J. Cancer Causes Control. Maternal use of household pesticides during pregnancy and risk of neuroblastoma in offspring. A pooled analysis of the ESTELLE and ESCALE French studies (SFCE). Epub ahead of print 10.1007/s10552-017-0944-5 (2017)

Bailey HD, Lacour B, Guerrini-Rousseau L, Bertozzi A, Leblond P, Faure-Conter C, Pellier I, Freycon C, Doz F, Puget S, Ducassou S, Orsi L, Clavel J. Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France). Cancer Causes Control. 28(7):719-32 (2017)

Bailey HD, Rios P, Lacour B, Guerrini-Rousseau L, Bertozzi AI, Leblond P, Faure-Conter C, Pellier I, Freycon C, Michon J, Puget S, Ducassou S, Orsi L, Clavel J. Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France) Int J Cancer. 140(8):1757-69. (2017)

PhDs

Roula Ajrouche, « Facteurs de risque des leucémies de l'enfant » (dir. J. Rudant et J. Clavel), Université Paris-Sud, defended in 2015

Paula Rios, «Facteurs de risque environnementaux et périnataux des neuroblastomes de l'enfant » (dir. J. Clavel), Université Paris-Descartes, defended in 2019

Nicolas Vidart, «Facteurs de risque environnementaux des tumeurs cérébrales de l'enfant » (dir. J. Clavel), Université Paris-Descartes, defended in 2019

Villejuif

INSERM
UMRS1153 Equipe 7
Bâtiment 15/16
16 avenue Paul Vaillant Couturier
94807 Villejuif Cedex

+33 (0)1 45 59 50 37
rnhe@inserm.fr

Nancy

Faculté de Médecine
BP 20199
9 avenue de la Forêt de Haye
54505 Vandoeuvre les Nancy Cedex

+33 (0)3 72 74 63 26
rntse@inserm.fr