Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jan 12:16:13.
doi: 10.1186/s12885-015-2028-9.

GENESIS: a French national resource to study the missing heritability of breast cancer

Olga M Sinilnikova  1   2 , Marie-Gabrielle Dondon  3   4   5   6 , Séverine Eon-Marchais  7   8   9   10 , Francesca Damiola  11 , Laure Barjhoux  12 , Morgane Marcou  13   14   15   16 , Carole Verny-Pierre  17 , Valérie Sornin  18 , Lucie Toulemonde  19   20   21   22 , Juana Beauvallet  23   24   25   26 , Dorothée Le Gal  27   28   29   30 , Noura Mebirouk  31   32   33   34 , Muriel Belotti  35 , Olivier Caron  36 , Marion Gauthier-Villars  37 , Isabelle Coupier  38   39 , Bruno Buecher  40 , Alain Lortholary  41 , Catherine Dugast  42 , Paul Gesta  43 , Jean-Pierre Fricker  44 , Catherine Noguès  45 , Laurence Faivre  46   47 , Elisabeth Luporsi  48 , Pascaline Berthet  49 , Capucine Delnatte  50 , Valérie Bonadona  51   52   53 , Christine M Maugard  54   55 , Pascal Pujol  56   57 , Christine Lasset  58   59   60 , Michel Longy  61 , Yves-Jean Bignon  62 , Claude Adenis  63 , Laurence Venat-Bouvet  64 , Liliane Demange  65 , Hélène Dreyfus  66   67 , Marc Frenay  68 , Laurence Gladieff  69 , Isabelle Mortemousque  70 , Séverine Audebert-Bellanger  71 , Florent Soubrier  72 , Sophie Giraud  73 , Sophie Lejeune-Dumoulin  74 , Annie Chevrier  75 , Jean-Marc Limacher  76 , Jean Chiesa  77 , Anne Fajac  78 , Anne Floquet  79 , François Eisinger  80   81 , Julie Tinat  82 , Chrystelle Colas  83 , Sandra Fert-Ferrer  84 , Clotilde Penet  85   86 , Thierry Frebourg  87 , Marie-Agnès Collonge-Rame  88 , Emmanuelle Barouk-Simonet  89 , Valérie Layet  90 , Dominique Leroux  91 , Odile Cohen-Haguenauer  92 , Fabienne Prieur  93 , Emmanuelle Mouret-Fourme  94 , François Cornélis  95 , Philippe Jonveaux  96 , Odile Bera  97 , Eve Cavaciuti  98   99   100   101 , Anne Tardivon  102 , Fabienne Lesueur  103   104   105   106 , Sylvie Mazoyer  107 , Dominique Stoppa-Lyonnet  108   109   110   111 , Nadine Andrieu  112   113   114   115
Affiliations

GENESIS: a French national resource to study the missing heritability of breast cancer

Olga M Sinilnikova et al. BMC 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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Cumulative number of index case inclusions over time. Legend: formula image Index cases with retrospective molecular diagnosis. formula image Index cases with prospective molecular diagnosis
See this image and copyright information in PMC

References

    1. Inca. Synthèse de l’activité d’oncogénétique 2012 - Consultations et laboratoires. BILONCOGEN13. 2014. Available: http://www.e-cancer.fr/Expertises-et-publications/Catalogue-des-publicat... [Accessed 11 26 2014]. 2014.
    1. Antoniou AC, Easton DF. Models of genetic susceptibility to breast cancer. Oncogene. 2006;25:5898–905. doi: 10.1038/sj.onc.1209879. - DOI - PubMed
    1. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013;45:371–2. doi: 10.1038/ng.2566. - DOI - PMC - PubMed
    1. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013;45:353–2. doi: 10.1038/ng.2563. - DOI - PMC - PubMed
    1. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447:1087–93. doi: 10.1038/nature05887. - DOI - PMC - PubMed

Publication types

Supplementary concepts