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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 Cox 1 Elsa Curtit 2 Gilles Romieu 3 Pierre Fumoleau 4 Maria Rios 5 Hervé Bonnefoi 6 Thomas Bachelot 7 Patrick Soulié 8 Christelle Jouannaud 9 Hugues Bourgeois 10 Thierry Petit 11 Isabelle Tennevet 12 David Assouline 13 Marie-Christine Mathieu 14 Jean-Philippe Jacquin 15 Sandrine Lavau-Denes 16 Ariane Darut-Jouve 17 Jean-Marc Ferrero 18 Carole Tarpin 19 Christelle Lévy 20 Valérie Delecroix 21, 22 Véronique Trillet-Lenoir 23 Oana Cojocarasu 24 Jérôme Meunier 25 Jean-Yves Pierga 26 Céline Faure-Mercier 27 Hélène Blanché 28 Mourad Sahbatou 28 Anne Boland 29 Delphine Bacq 29 Céline Besse Jean-François Deleuze 28, 29 Iris Pauporté 27 Gilles Thomas 30 Xavier Pivot 2
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=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). 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.
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David Cox, Elsa Curtit, Gilles Romieu, Pierre Fumoleau, Maria Rios, et al.. GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients . Oncotarget, Impact journals, 2016, ⟨10.18632/oncotarget.12669⟩. ⟨hal-01391480⟩

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