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Research Papers:

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

David G. Cox _, Elsa Curtit, Gilles Romieu, Pierre Fumoleau, Maria Rios, Hervé Bonnefoi, Thomas Bachelot, Patrick Soulié, Christelle Jouannaud, Hugues Bourgeois, Thierry Petit, Isabelle Tennevet, David Assouline, Marie-Christine Mathieu, Jean-Philippe Jacquin, Sandrine Lavau-Denes, Ariane Darut-Jouve, Jean-Marc Ferrero, Carole Tarpin, Christelle Lévy, Valérie Delecroix, Véronique Trillet-Lenoir, Oana Cojocarasu, Jérôme Meunier, Jean-Yves Pierga, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Jean-François Deleuze, Iris Pauporté, Gilles Thomas, Xavier Pivot

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Abstract

David G. Cox1, Elsa Curtit2, Gilles Romieu3, Pierre Fumoleau4, Maria Rios5, Hervé Bonnefoi6, Thomas Bachelot7, Patrick Soulié8, Christelle Jouannaud9, Hugues Bourgeois10, Thierry Petit11, Isabelle Tennevet12, David Assouline13, Marie-Christine Mathieu14, Jean-Philippe Jacquin15, Sandrine Lavau-Denes16, Ariane Darut-Jouve17, Jean-Marc Ferrero18, Carole Tarpin19, Christelle Lévy20, Valérie Delecroix21, Véronique Trillet-Lenoir22, Oana Cojocarasu23, Jérôme Meunier24, Jean-Yves Pierga25, Céline Faure-Mercier26, Hélène Blanché27, Mourad Sahbatou27, Anne Boland28, Delphine Bacq28, Céline Besse28, Jean-François Deleuze27,28, Iris Pauporté26, Gilles Thomas29, Xavier Pivot2

1Centre de Recherche en Cancérologie de Lyon, INSERM U1052 - Centre Léon Bérard, 69373 Lyon, France

2Hôpital Jean-Minjoz, Centre Hospitalier Universitaire, Boulevard Fleming, 25030 Besançon, France

3Oncologie Sénologie, ICM Institut Régional du Cancer, 34298 Montpellier Cedex, France

4Georges-François Leclerc, 21000 Dijon, France

5Institut de Cancérologie de Lorraine - Alexis Vautrin, Département d’Oncologie Médicale, 54511 Vandœuvre-lès-Nancy Cedex, France

6Institut Bergonié, Département d’Oncologie Médicale, 33000 Bordeaux, France

7Centre Léon Bérard, Département de Cancérologie Médicale, Lyon Cedex 08, France

8Institut de Cancérologie de l’Ouest, Service Oncologie Médicale, 49993 Angers Cedex 09, France

9Institut Jean Godinot, Service Oncologie Médicale, 51056 Reims Cedex, France

10Clinique Victor Hugo-Centre Jean Bernard, 72015 Le Mans Cedex 2, France

11Centre Paul Strauss, Service d’Oncologie Médicale, 67065 Strasbourg Cedex, France

12Centre Henri Becquerel, rue d’Amiens, 76038 Rouen, France

13Institut Daniel Hollard, Service Oncologie Médicale, 38028 Grenoble Cedex 01, France

14Institut Gustave Roussy, Comité de Pathologie Mammaire, 94805 Villejuif Cedex, France

15Institut de Cancérologie Lucien Neuwirth, Service Oncologie Médicale, 42270 Saint Priest en Jarez, France

16Centre Hospitalier de Limoges, Service d’Oncologie Médicale, 87042 Limoges Cedex, France

17Clinique Drévon, Centre d’Oncologie et de Radiothérapie du Parc, 21000 Dijon, France

18Centre Antoine Lacassagne, Département Oncologie Médicale, 06189 Nice Cedex 02, France

19Institut Paoli-Calmettes, Département d’Oncologie Médicale, 13009 Marseille, France

20Centre François Baclesse, 14076 Caen Cedex 5, France

21Pôle Mutualiste, Service Oncologie Médicale, 44606 Saint Nazaire, France

22Centre Hospitalier Lyon Sud, Service d’Oncologie Médicale, 69495 Pierre-Benite cedex, France

23Centre Hospitalier Le Mans, Service d’Onco-Hématologie et Médecine interne, 72037 Le Mans Cedex, France

24Centre Hospitalier Régional d’Orléans, Service d’Oncologie Médicale, 45032 Orleans Cedex 1, France

25Institut Curie, Department of Medical Oncology, 75248 Paris Cedex 05, France

26Institut National du Cancer, Direction de la Recherche, 92513 Boulogne-Billancourt, France

27Fondation Jean Dausset, Centre d’Etudes du Polymorphisme Humain, 75010 Paris, France

28Centre National du Génotypage, Institut de Génomique, CEA, CP 5721, 91057 Evry Cedex, France

29Synergie Lyon Cancer, Centre Léon Bérard, Lyon Cedex 08, France

Correspondence to:

David G. Cox, email: david.cox@inserm.fr

Keywords: breast, estrogen receptor, HER2, association, GWAS

Received: April 12, 2016    Accepted: September 14, 2016    Published: October 14, 2016

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.

Author Information

David G. Cox
Primary Contact  _

Elsa Curtit

Gilles Romieu

Pierre Fumoleau

Maria Rios

Hervé Bonnefoi

Thomas Bachelot

Patrick Soulié

Christelle Jouannaud

Hugues Bourgeois

Thierry Petit

Isabelle Tennevet

David Assouline

Marie-Christine Mathieu

Jean-Philippe Jacquin

Sandrine Lavau-Denes

Ariane Darut-Jouve

Jean-Marc Ferrero

Carole Tarpin

Christelle Lévy

Valérie Delecroix

Véronique Trillet-Lenoir

Oana Cojocarasu

Jérôme Meunier

Jean-Yves Pierga

Céline Faure-Mercier

Hélène Blanché

Mourad Sahbatou

Anne Boland

Delphine Bacq

Céline Besse

Jean-François Deleuze

Iris Pauporté

Gilles Thomas

Xavier Pivot


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