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 1, 2, * Xavier Pivot 1 Julie Henriques 3 Sophie Paget-Bailly 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 Véronique Trillet-Lenoir 22 Oana Cojocarasu 23 Jérôme Meunier 24 Jean-Yves Pierga 25 Pierre Kerbrat 26 Céline Faure-Mercier 27 Hélène Blanché 28 Mourad Sahbatou 28 Anne Boland 29 Delphine Bacq 29 Céline Besse 29 Gilles Thomas 30 Jean-François Deleuze 28, 29 Iris Pauporté 27 Gilles Romieu 31 David Cox 32, *
* Auteur correspondant
1 HOTE GREFFON - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC
2 Service d'Oncologie Médicale [Besançon]
3 UMQVC - Unité de Méthodologie et de Qualité de Vie en Cancérologie
CEF2P / CARCINO - Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC, Pôle cancérologie (CHU Besançon), IRFC - Institut Régional Fédératif du Cancer
4 Département d'oncologie médicale [Centre Georges-François Leclerc]
5 Département d’Oncologie Médicale [Vandoeuvre Les Nancy]
6 Département d'oncologie médicale
7 Département de Cancérologie Médicale [Lyon]
8 Service Oncologie Médicale [Angers]
9 Service Oncologie Médicale [Reims]
10 Centre Jean Bernard [Le Mans]
11 Service d’Oncologie Médicale [Strasbourg]
12 Département d'oncologie médicale [Rouen]
13 Service Oncologie Médicale [Grenoble]
14 Pathologie mammaire
Département de médecine oncologique [Gustave Roussy]
15 Service Oncologie Médicale [Saint Priest en Jarez]
16 Service d'Oncologie médicale [CHU Limoges]
17 Centre d’oncologie et de radiothérapie du Parc [Dijon]
18 Département Oncologie Médicale [Nice]
19 Département d’Oncologie Médicale [Marseille]
20 Service d'Oncologie Médicale [Caen]
21 Pôle Mutualiste - Service Oncologie Médicale [Saint-Nazaire]
22 Service d’Oncologie Médicale [CHU Lyon Sud]
23 Service d’Onco-Hématologie et Médecine interne [Le Mans]
24 Service d’Oncologie médicale [Orleans]
25 Département d'Oncologie Médicale [Paris]
26 Service d'Oncologie Médicale [Rennes]
27 Direction de la Recherche [Boulogne-Billancourt]
28 Centre de Ressources Biologiques [Paris]
29 Centre de Ressources Biologiques [Evry]
30 Synergie Lyon Cancer [Lyon]
31 Oncologie Sénologie [Montpellier]
32 CRCL - Centre de Recherche en Cancérologie de Lyon
Abstract : AbstractBackgroundGenome-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.MethodsA 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.ResultsThe 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.ConclusionsIn 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 registrationPHARE cohort: NCT00381901, Sept. 26, 2006 – SIGNAL cohort: INCa RECF1098, Jan. 28, 2009
Keywords : Genetic variant Single nucleotide polymorphism Risk score Prognosis Breast cancer
Type de document :
Article dans une revue
Breast Cancer Research, BioMed Central, 2016, 19 (1), pp.98. 〈10.1186/s13058-017-0888-4〉
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Elsa Curtit, Xavier Pivot, Julie Henriques, Sophie Paget-Bailly, Pierre Fumoleau, et al.. 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. Breast Cancer Research, BioMed Central, 2016, 19 (1), pp.98. 〈10.1186/s13058-017-0888-4〉. 〈inserm-01577637〉

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