Constitutional variants are not associated with HER2-positive breast cancer: results from the SIGNAL/PHARE clinical cohort

Autor: Maria Rios, Alexia Renaud, Valérie Delecroix, Oana Cojocarasu, Céline Besse, Fabien Calvo, Mourad Sahbatou, Véronique Trillet-Lenoir, Ariane Darut-Jouve, Sandrine Lavau-Denes, Patrick Soulié, Hélène Blanché, Hervé Bonnefoi, Marie-Christine Mathieu, Céline Faure-Mercier, David G. Cox, Jean-Yves Pierga, Christelle Jouannaud, Thierry Petit, Jean-Marc Ferrero, Pierre Kerbrat, Christelle Levy, Carole Tarpin, Thomas Bachelot, Jérôme Meunier, Anne Boland, David Assouline, Gilles Romieu, Jean-François Deleuze, Cécile Agostini, Gilles Thomas, Isabelle Tennevet, Delphine Bacq, Jean-Philippe Jacquin, Iris Pauporté, Pierre Fumoleau, Xavier Pivot, Hugues Bourgeois
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: NPJ Breast Cancer
npj Breast Cancer, Vol 3, Iss 1, Pp 1-5 (2017)
ISSN: 2374-4677
Popis: Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case–case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098). The main goal was to identify variants specifically related to human epidermal growth factor receptor 2-positive breast cancer. A two-staged genotyping strategy was carried out to cover as large a proportion of the genome as possible. All subjects were genotyped using the Illumina HumanCore Exome chip set. Principal Components Analysis and k-means were then used to characterize the ancestry of the participants. A random sample of subjects from the main “European” cluster was genotyped with the Omni5 chip set. These data were then used to impute missing genotypes from the remaining subjects genotyped only using the HumanCore Exome array. From the 9836 patients, a total of 8703 cases including 3230 patients with human epidermal growth factor receptor 2-positive breast cancer were analyzed. Despite having 80% power to detect an odds ratio of 1.23 in this population, no variant achieved genome-wide significance for association with the occurrence of human epidermal growth factor receptor 2–positive breast cancer vs. any other subtype of breast tumour. Our study was unable to identify constitutional polymorphisms that are strongly associated with human epidermal growth factor receptor 2-positive status among breast cancer patients.
Genetics: heredity does not explain HER2 expression A large gene-finding study failed to identify any hereditary factors linked to HER2 expression among women with breast cancer. A team in France led by Xavier Pivot from the University Hospital Center of Besançon, France, analyzed more than 500,000 single DNA letters from a cohort of 8703 patients with breast cancer, 3230 of whom had tumors with high expression of human epidermal growth factor receptor 2 (HER2) and are thus treated with for anti-HER2 targeted therapies. The researchers searched for DNA variants associated with HER2 status, but none reached the threshold for statistical significance. The findings reveal a high level of genetic diversity in women with HER2-positive breast cancer and suggest that HER2 amplification may have more to do with the intrinsic nature of the tumor than with the genetics of the patient.
Databáze: OpenAIRE
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