Registre National des Cancers de l’Enfant

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

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