title: GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients.
abstract: Genetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46×10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16×10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors.
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, INSERM U1052 - Centre Léon Bérard, 69373 Lyon, France.
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.affiliation: Hôpital Jean-Minjoz, Centre Hospitalier Universitaire, Boulevard Fleming, 25030 Besançon, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Curtit
authors.affiliation: Oncologie Sénologie, ICM Institut Régional du Cancer, 34298 Montpellier Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Georges-François Leclerc, 21000 Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.affiliation: Institut de Cancérologie de Lorraine - Alexis Vautrin, Département d'Oncologie Médicale, 54511 Vandœuvre-lès-Nancy Cedex, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Rios
authors.affiliation: Institut Bergonié, Département d'Oncologie Médicale, 33000 Bordeaux, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: Centre Léon Bérard, Département de Cancérologie Médicale, Lyon Cedex 08, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Institut de Cancérologie de l'Ouest, Service Oncologie Médicale, 49993 Angers Cedex 09, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Soulié
authors.affiliation: Institut Jean Godinot, Service Oncologie Médicale, 51056 Reims Cedex, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Jouannaud
authors.affiliation: Clinique Victor Hugo-Centre Jean Bernard, 72015 Le Mans Cedex 2, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Bourgeois
authors.affiliation: Centre Paul Strauss, Service d'Oncologie Médicale, 67065 Strasbourg Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Petit
authors.affiliation: Centre Henri Becquerel, rue d'Amiens, 76038 Rouen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tennevet
authors.affiliation: Institut Daniel Hollard, Service Oncologie Médicale, 38028 Grenoble Cedex 01, France.
authors.forename: David
authors.initials: D
authors.lastname: Assouline
authors.affiliation: Institut Gustave Roussy, Comité de Pathologie Mammaire, 94805 Villejuif Cedex, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mathieu
authors.affiliation: Institut de Cancérologie Lucien Neuwirth, Service Oncologie Médicale, 42270 Saint Priest en Jarez, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jacquin
authors.affiliation: Centre Hospitalier de Limoges, Service d'Oncologie Médicale, 87042 Limoges Cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lavau-Denes
authors.affiliation: Clinique Drévon, Centre d'Oncologie et de Radiothérapie du Parc, 21000 Dijon, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Darut-Jouve
authors.affiliation: Centre Antoine Lacassagne, Département Oncologie Médicale, 06189 Nice Cedex 02, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: Institut Paoli-Calmettes, Département d'Oncologie Médicale, 13009 Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Tarpin
authors.affiliation: Centre François Baclesse, 14076 Caen Cedex 5, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Lévy
authors.affiliation: Pôle Mutualiste, Service Oncologie Médicale, 44606 Saint Nazaire, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Delecroix
authors.affiliation: Centre Hospitalier Lyon Sud, Service d'Oncologie Médicale, 69495 Pierre-Benite cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Trillet-Lenoir
authors.affiliation: Centre Hospitalier Le Mans, Service d'Onco-Hématologie et Médecine interne, 72037 Le Mans Cedex, France.
authors.forename: Oana
authors.initials: O
authors.lastname: Cojocarasu
authors.affiliation: Centre Hospitalier Régional d'Orléans, Service d'Oncologie Médicale, 45032 Orleans Cedex 1, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Meunier
authors.affiliation: Institut Curie, Department of Medical Oncology, 75248 Paris Cedex 05, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Institut National du Cancer, Direction de la Recherche, 92513 Boulogne-Billancourt, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Faure-Mercier
authors.affiliation: Fondation Jean Dausset, Centre d'Etudes du Polymorphisme Humain, 75010 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Blanché
authors.affiliation: Fondation Jean Dausset, Centre d'Etudes du Polymorphisme Humain, 75010 Paris, France.
authors.forename: Mourad
authors.initials: M
authors.lastname: Sahbatou
authors.affiliation: Centre National du Génotypage, Institut de Génomique, CEA, CP 5721, 91057 Evry Cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.affiliation: Centre National du Génotypage, Institut de Génomique, CEA, CP 5721, 91057 Evry Cedex, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bacq
authors.affiliation: Centre National du Génotypage, Institut de Génomique, CEA, CP 5721, 91057 Evry Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Besse
authors.affiliation: Fondation Jean Dausset, Centre d'Etudes du Polymorphisme Humain, 75010 Paris, France.|Centre National du Génotypage, Institut de Génomique, CEA, CP 5721, 91057 Evry Cedex, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Institut National du Cancer, Direction de la Recherche, 92513 Boulogne-Billancourt, France.
authors.forename: Iris
authors.initials: I
authors.lastname: Pauporté
authors.affiliation: Synergie Lyon Cancer, Centre Léon Bérard, Lyon Cedex 08, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Hôpital Jean-Minjoz, Centre Hospitalier Universitaire, Boulevard Fleming, 25030 Besançon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics*; D017326:Clinical Trials, Phase III as Topic; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D011960:Receptors, Estrogen; C496353:FGFR2 protein, human
keywords: GWAS; HER2; association; breast; estrogen receptor