title: GENESIS: a French national resource to study the missing heritability of breast cancer.
abstract: BACKGROUND
  Less than 20% of familial breast cancer patients who undergo genetic testing for BRCA1 and BRCA2 carry a pathogenic mutation in one of these two genes. The GENESIS (GENE SISter) study was designed to identify new breast cancer susceptibility genes in women attending cancer genetics clinics and with no BRCA1/2 mutation.
  
  
  METHODS
  The study involved the French national network of family cancer clinics. It was based on enrichment in genetic factors of the recruited population through case selection relying on familial criteria, but also on the consideration of environmental factors and endophenotypes like mammary density or tumor characteristics to assess potential genetic heterogeneity. One of the initial aims of GENESIS was to recruit affected sibpairs. Siblings were eligible when index cases and at least one affected sister were diagnosed with infiltrating mammary or ductal adenocarcinoma, with no BRCA1/2 mutation. In addition, unrelated controls and unaffected sisters were recruited. The enrolment of patients, their relatives and their controls, the collection of the clinical, epidemiological, familial and biological data were centralized by a coordinating center.
  
  
  RESULTS
  Inclusion of participants started in February 2007 and ended in December 2013. A total of 1721 index cases, 826 affected sisters, 599 unaffected sisters and 1419 controls were included. 98% of participants completed the epidemiological questionnaire, 97% provided a blood sample, and 76% were able to provide mammograms. Index cases were on average 59 years old at inclusion, were born in 1950, and were 49.7 years of age at breast cancer diagnosis. The mean age at diagnosis of affected sisters was slightly higher (51.4 years). The representativeness of the control group was verified.
  
  
  CONCLUSIONS
  The size of the study, the availability of biological specimens and the clinical data collection together with the detailed and complete epidemiological questionnaire make this a unique national resource for investigation of the missing heritability of breast cancer, by taking into account environmental and life style factors and stratifying data on endophenotypes to decrease genetic heterogeneity.
authors.affiliation: Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France.|Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
authors.affiliation: Inserm, U900, Paris, France. mariegabrielle.dondon@curie.fr.|Institut Curie, Paris, France. mariegabrielle.dondon@curie.fr.|PSL Research University, Paris, France. mariegabrielle.dondon@curie.fr.|Mines ParisTech, Fontainebleau, France. mariegabrielle.dondon@curie.fr.
authors.forename: Marie-Gabrielle
authors.initials: MG
authors.lastname: Dondon
authors.affiliation: Inserm, U900, Paris, France. severine.eonmarchais@curie.fr.|Institut Curie, Paris, France. severine.eonmarchais@curie.fr.|PSL Research University, Paris, France. severine.eonmarchais@curie.fr.|Mines ParisTech, Fontainebleau, France. severine.eonmarchais@curie.fr.
authors.forename: Séverine
authors.initials: S
authors.lastname: Eon-Marchais
authors.affiliation: Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France. francesca.damiola@lyon.unicancer.fr.
authors.forename: Francesca
authors.initials: F
authors.lastname: Damiola
authors.affiliation: Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France. laure.barjhoux@lyon.unicancer.fr.
authors.forename: Laure
authors.initials: L
authors.lastname: Barjhoux
authors.affiliation: Inserm, U900, Paris, France. morgane.marcou@apr.aphp.fr.|Institut Curie, Paris, France. morgane.marcou@apr.aphp.fr.|PSL Research University, Paris, France. morgane.marcou@apr.aphp.fr.|Mines ParisTech, Fontainebleau, France. morgane.marcou@apr.aphp.fr.
authors.forename: Morgane
authors.initials: M
authors.lastname: Marcou
authors.affiliation: Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France. carole.verny@lyon.unicancer.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Verny-Pierre
authors.affiliation: Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France. valerie.sornin@lyon.unicancer.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Sornin
authors.affiliation: Inserm, U900, Paris, France. lucietoulemonde@hotmail.com.|Institut Curie, Paris, France. lucietoulemonde@hotmail.com.|PSL Research University, Paris, France. lucietoulemonde@hotmail.com.|Mines ParisTech, Fontainebleau, France. lucietoulemonde@hotmail.com.
authors.forename: Lucie
authors.initials: L
authors.lastname: Toulemonde
authors.affiliation: Inserm, U900, Paris, France. juana.beauvallet@curie.fr.|Institut Curie, Paris, France. juana.beauvallet@curie.fr.|PSL Research University, Paris, France. juana.beauvallet@curie.fr.|Mines ParisTech, Fontainebleau, France. juana.beauvallet@curie.fr.
authors.forename: Juana
authors.initials: J
authors.lastname: Beauvallet
authors.affiliation: Inserm, U900, Paris, France. dorothee.legal@curie.fr.|Institut Curie, Paris, France. dorothee.legal@curie.fr.|PSL Research University, Paris, France. dorothee.legal@curie.fr.|Mines ParisTech, Fontainebleau, France. dorothee.legal@curie.fr.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Le Gal
authors.affiliation: Inserm, U900, Paris, France. noura.mebirouk@curie.fr.|Institut Curie, Paris, France. noura.mebirouk@curie.fr.|PSL Research University, Paris, France. noura.mebirouk@curie.fr.|Mines ParisTech, Fontainebleau, France. noura.mebirouk@curie.fr.
authors.forename: Noura
authors.initials: N
authors.lastname: Mebirouk
authors.affiliation: Institut Curie, Service de Génétique, Paris, France. muriel.belotti@curie.fr.
authors.forename: Muriel
authors.initials: M
authors.lastname: Belotti
authors.affiliation: Institut de Cancérologie Gustave Roussy, Service d'Oncologie Génétique, Villejuif, France. olivier.caron@gustaveroussy.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
authors.affiliation: Institut Curie, Service de Génétique, Paris, France. marion.gauthier-villars@curie.fr.
authors.forename: Marion
authors.initials: M
authors.lastname: Gauthier-Villars
authors.affiliation: Hôpital Arnaud de Villeneuve, CHU Montpellier, Service de Génétique médicale et Oncogénétique, Montpellier, France. i-coupier@chu-montpellier.fr.|ICM Val d'Aurel, Unité d'Oncogénétique, Montpellier, France. i-coupier@chu-montpellier.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.affiliation: Institut Curie, Service de Génétique, Paris, France. bruno.buecher@curie.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.affiliation: Centre Catherine de Sienne, Service d'Oncologie Médicale, Nantes, France. lortholary.alain@catherinedesienne.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.affiliation: Centre Eugène-Marquis, Service de Génétique, Rennes, France. c.dugast@rennes.unicancer.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dugast
authors.affiliation: CH Georges Renon, Service Oncogénétique pour la consultation oncogénétique régionale Poitou-Charentes, Niort, France. paul.gesta@ch-niort.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Gesta
authors.affiliation: Centre Paul Strauss, Unité d'Oncologie, Strasbourg, France. jfricker@strasbourg.unicancer.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.affiliation: Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. catherine.nogues@curie.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.affiliation: Hôpital d'Enfants, Service de Génétique Médicale, Dijon, France. laurence.faivre@chu-dijon.fr.|Centre Georges François Leclerc, Oncogénétique, Dijon, France. laurence.faivre@chu-dijon.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: ICL Alexis Vautrin, Unité d'Oncogénétique, Vandœuvre-lès-Nancy, France. e.luporsi@nancy.unicancer.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
authors.affiliation: Centre François Baclesse, Unité de pathologie gynécologique, Caen, France. p.berthet@baclesse.fr.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.affiliation: Centre René Gauducheau, Unité d'Oncogénétique, Nantes Saint Herblain, France. capucine.delnatte@ico.unicancer.fr.
authors.forename: Capucine
authors.initials: C
authors.lastname: Delnatte
authors.affiliation: Université Claude Bernard Lyon 1, Villeurbanne, France. valerie.bonadona@lyon.unicancer.fr.|CNRS UMR 5558, Lyon, France. valerie.bonadona@lyon.unicancer.fr.|Centre Léon Bérard, Unité de Prévention et Epidémiologie Génétique, Lyon, France. valerie.bonadona@lyon.unicancer.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.affiliation: Hôpitaux Universitaires de Strasbourg, UF1422 Oncogénétique moléculaire, Laboratoire de diagnostic génétique, Strasbourg, France. christine.maugard@chru-strasbourg.fr.|Hôpitaux Universitaires de Strasbourg, UF6948 Oncogénétique, Service d'Hémato-Oncologie, Strasbourg, France. christine.maugard@chru-strasbourg.fr.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Maugard
authors.affiliation: Hôpital Arnaud de Villeneuve, CHU Montpellier, Service de Génétique médicale et Oncogénétique, Montpellier, France. p-pujol@chu-montpellier.fr.|Inserm, U896, CRCM Val d'Aurel, Montpellier, France. p-pujol@chu-montpellier.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.affiliation: Université Claude Bernard Lyon 1, Villeurbanne, France. christine.lasset@lyon.unicancer.fr.|CNRS UMR 5558, Lyon, France. christine.lasset@lyon.unicancer.fr.|Centre Léon Bérard, Unité de Prévention et Epidémiologie Génétique, Lyon, France. christine.lasset@lyon.unicancer.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.affiliation: Institut Bergonié, Bordeaux, France. m.longy@bordeaux.unicancer.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.affiliation: Centre Jean-Perrin, Clermont-Ferrand, France. yves-jean.bignon@cjp.fr.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.affiliation: Centre Oscar-Lambret, Lille, France. cl-adenis@o-lambret.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Adenis
authors.affiliation: Hôpital Universitaire Dupuytren, Service d'Oncologie Médicale, Limoges, France. laurence.venat@chu-limoges.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Venat-Bouvet
authors.affiliation: Polyclinique Courlancy, Reims, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Demange
authors.affiliation: Clinique Sainte Catherine, Avignon, France. h.dreyfus@isc84.org.|CHU de Grenoble, Hôpital Couple-Enfant, Département de Génétique, Grenoble, France. h.dreyfus@isc84.org.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dreyfus
authors.affiliation: Centre Antoine Lacassagne, Unité d'Oncogénétique, Nice, France. marc.frenay@nice.unicancer.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Frenay
authors.affiliation: Institut Claudius Regaud - IUCT-Oncopole, Service d'Oncologie Médicale, Toulouse, France. gladieff.laurence@iuct-oncopole.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.affiliation: Hôpital Bretonneau, Service de Génétique, Tours, France. i.mortemousque@chu-tours.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mortemousque
authors.affiliation: CHU Brest, Hôpital Morvan, Département de génétique médicale en pédiatrie, Brest, France. severine.audebert@chu-brest.fr.
authors.forename: Séverine
authors.initials: S
authors.lastname: Audebert-Bellanger
authors.affiliation: Hôpital Tenon, Paris, France. florent.soubrier@psl.aphp.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
authors.affiliation: Hôpital Edouard Herriot, Service de Génétique Moléculaire, Lyon, France. sophie.giraud@chu-lyon.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.affiliation: Hôpital Jeanne de Flandre, Service de génétique clinique Guy Fontaine, Lille, France. sophie.lejeune@chru-lille.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lejeune-Dumoulin
authors.affiliation: Hôpital Universitaire de Rouen, Département de Génétique, Rouen, France. annie.chevrier@chu-rouen.fr.
authors.forename: Annie
authors.initials: A
authors.lastname: Chevrier
authors.affiliation: Hôpital Pasteur, Service d'Onco-hématologie, Colmar, France. limacher@transgene.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Limacher
authors.affiliation: CHRU Hôpital Caremeau, Nîmes, France. jean.chiesa@chu-nimes.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Chiesa
authors.affiliation: Hôpital Tenon, Service d'Oncogénétique, Paris, France. anne.fajac@tnn.aphp.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Fajac
authors.affiliation: Institut Bergonié, Bordeaux, France. a.floquet@bordeaux.unicancer.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Floquet
authors.affiliation: IPC, Département d'Anticipation et de Suivi des Cancers, Marseille, France. eisingerf@ipc.unicancer.fr.|Inserm, UMR 912, Marseille, France. eisingerf@ipc.unicancer.fr.
authors.forename: François
authors.initials: F
authors.lastname: Eisinger
authors.affiliation: Hôpital Universitaire de Rouen, Département de Génétique, Rouen, France. julie.tinat@chu-rouen.fr.
authors.forename: Julie
authors.initials: J
authors.lastname: Tinat
authors.affiliation: Groupe Hospitalier Pitié-Salpêtrière, Département de Génétique, APHP, Paris, France. chrystelle.colas@psl.aphp.fr.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.affiliation: Centre Hospitalier de Chambéry, Chambéry, France. sandra.fertferrer@ch-chambery.fr.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fert-Ferrer
authors.affiliation: Institut Jean-Godinot, Reims, France. cpenet@iccreims.fr.|ICC Courlancy, Cs Oncogénétique, Reims, France. cpenet@iccreims.fr.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Penet
authors.affiliation: Hôpital Universitaire de Rouen, Département de Génétique, Rouen, France. thierry.frebourg@chu-rouen.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: CHU Hôpital Saint-Jacques, Service Génétique et Biologie du Développement - Histologie, Besançon, France. macollongerame@chu-besancon.fr.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Collonge-Rame
authors.affiliation: Institut Bergonié, Bordeaux, France. e.barouksimonet@bordeaux.unicancer.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Barouk-Simonet
authors.affiliation: Hôpital Flaubert, Le Havre, France. vlayet@ch-havre.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Layet
authors.affiliation: CHU de Grenoble, Hôpital Couple-Enfant, Département de Génétique, Grenoble, France. dleroux@chu-grenoble.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.affiliation: Hôpital Saint-Louis, Paris, France. odile.cohen-haguenauer@sls.aphp.fr.
authors.forename: Odile
authors.initials: O
authors.lastname: Cohen-Haguenauer
authors.affiliation: CHU de Saint-Etienne, Hôpital Nord, Service de Génétique, Saint-Etienne, France. fabienne.prieur@chu-st-etienne.fr.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Prieur
authors.affiliation: Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. emmanuelle.fourme@curie.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mouret-Fourme
authors.affiliation: Hôpital Lariboisière, Centre Viggo-Petersen, Paris, France. fcornelis@chu-clermontferrand.fr.
authors.forename: François
authors.initials: F
authors.lastname: Cornélis
authors.affiliation: CHU Hôpital de Brabois, Laboratoire de Génétique, Vandœuvre-lès-Nancy, France. p.jonveaux@chu-nancy.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.affiliation: CHU de Martinique, Unité d'Oncogénétique, Fort-de-France, France. odile.bera@chu-fortdefrance.fr.
authors.forename: Odile
authors.initials: O
authors.lastname: Bera
authors.affiliation: Inserm, U900, Paris, France. eve.cavaciuti@curie.fr.|Institut Curie, Paris, France. eve.cavaciuti@curie.fr.|PSL Research University, Paris, France. eve.cavaciuti@curie.fr.|Mines ParisTech, Fontainebleau, France. eve.cavaciuti@curie.fr.
authors.forename: Eve
authors.initials: E
authors.lastname: Cavaciuti
authors.affiliation: Institut Curie, Département d'imagerie médicale, Paris, France. anne.tardivon@curie.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Tardivon
authors.affiliation: Inserm, U900, Paris, France. fabienne.lesueur@curie.fr.|Institut Curie, Paris, France. fabienne.lesueur@curie.fr.|PSL Research University, Paris, France. fabienne.lesueur@curie.fr.|Mines ParisTech, Fontainebleau, France. fabienne.lesueur@curie.fr.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.affiliation: Cancer Research Centre of Lyon, CNRS UMR5286, Inserm U1052, Université Claude Bernard Lyon 1, Centre Léon Bérard, Lyon, France. sylvie.mazoyer@lyon.unicancer.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.affiliation: PSL Research University, Paris, France. dominique.stoppa-lyonnet@curie.fr.|Institut Curie, Service de Génétique, Paris, France. dominique.stoppa-lyonnet@curie.fr.|Inserm, U830, Paris, France. dominique.stoppa-lyonnet@curie.fr.|Université Paris-Descartes, Paris, France. dominique.stoppa-lyonnet@curie.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.affiliation: Inserm, U900, Paris, France. nadine.andrieu@curie.fr.|Institut Curie, Paris, France. nadine.andrieu@curie.fr.|PSL Research University, Paris, France. nadine.andrieu@curie.fr.|Mines ParisTech, Fontainebleau, France. nadine.andrieu@curie.fr.
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009363:Neoplasm Proteins