Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes

Elsa Curtit, Xavier Pivot, Julie Henriques, Sophie Paget-Bailly, 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, Pierre Kerbrat, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Gilles Thomas, Jean-François Deleuze, Iris Pauporté, Gilles Romieu, David G Cox, Elsa Curtit, Xavier Pivot, Julie Henriques, Sophie Paget-Bailly, 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, Pierre Kerbrat, Céline Faure-Mercier, Hélène Blanché, Mourad Sahbatou, Anne Boland, Delphine Bacq, Céline Besse, Gilles Thomas, Jean-François Deleuze, Iris Pauporté, Gilles Romieu, David G Cox

Abstract

Background: Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer.

Methods: A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS.

Results: The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival.

Conclusions: In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis.

Trial registration: PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.

Keywords: Breast cancer; Genetic variant; Prognosis; Risk score; Single nucleotide polymorphism.

Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

This study was approved by the ethics committee of the University Hospital of Besançon. All study participants signed an informed consent form.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart
Fig. 2
Fig. 2
The 94-SNP risk score repartition among the breast cancer patient population: normal distribution. SNP single nucleotide polymorphism
Fig. 3
Fig. 3
No correlation between the 94-SNP risk score and pathological subtype of breast cancer. SNP single nucleotide polymorphism, ER estrogen receptor, HER2 human epidermal growth factor, ANOVA analysis of variance
Fig. 4
Fig. 4
Survival according to 94-SNP risk score quartiles. a Disease-free survival. b Overall survival. No relationship between invasive-disease-free survival (iDFS) or overall survival (OS) and the 94-SNP risk score. The p value and hazard ratio (HR) is from the test of trend from quartile (Q) 1 to quartile 4. SNP single nucleotide polymorphism

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