Abstract 2258: Genome-wide association studies of breast cancer prognosis
Notice bibliographique
Résumé
Abstract Introduction: The prognosis and response to treatment in women with breast cancer varies considerably after taking into account clinic-pathological variables. Other factors such as host genotype are also likely to be important. We therefore investigated the role of germline genetic variation on survival after breast cancer using data from the Breast Cancer Association Consortium. Materials and methods: We included data from ten projects in which breast cancer case cohorts were genotyped using arrays providing genome-wide coverage of common variants. The majority of samples was genotyped using the Illumina custom iCOGS or OncoArray chips. Data were imputed using the 1000 Genome phase 3 as a reference panel using a two-stage procedure. We assessed the association between genotype and 10-year breast cancer specific survival for each SNP using Cox proportional hazards regression adjusted for principle components and stratified by country. Genotype data from 87,877 breast cancer cases, 63,170 ER-positive and 20,297 ER-negative, with 6,511 known breast cancer deaths were included in the analyses. Results: Preliminary analyses shows that in all invasive cases, ER-positive and ER-negative disease 123, 110, and 212 variants respectively, were associated with breast cancer-specific mortality at P<5x10-5. A single variant, rs1295683, was associated with higher mortality at genome-wide significance in all patients: HR=1.16 (95%CI:1.10-1.22); P=2.8x10-8 (risk allele frequency: 0.12). We identified four variants to be associated with mortality in ER-negative disease at P<5x10-8. The strongest association was for rs145963877: HR=1.32 (95%CI:1.20-1.46); P=2.3x10-8. No variant reached genome-wide significance for ER-positive disease; the most significant variant was chr7:41400313 with an HR=1.17 (95%CI:1.10-1.24); P=1.8x10-7. In addition, using OncoArray data, we provided independent validation of higher mortality of CHEK2 c.1100delC carriers compared with non-carriers (HR=1.56 (95%CI:1.22-2.01)), previously reported in Weischer et al JCO 2012. Using iCOGS data, we evaluated the association between mortality and the polygenic risk score (PRS) based on 77 known breast cancer susceptibility SNPs. A higher PRS was significantly associated with lower breast cancer-specific mortality: HR=0.87(95%CI:0.81-0.93) (per unit of PRS) with a similar association in ER-negative and ER-positive disease. The association was attenuated after adjusting for tumor grade. Conclusion: We have identified a novel set of germline genetic variants that are associated with breast cancer prognosis. The effect sizes are small for each of the variants and unlikely to be of immediate clinical relevance. However, understanding of the biology that underlies the associations may identify novel pathways and targets for therapy. Being at higher risk of breast cancer, as defined by the breast cancer susceptibility PRS, is not associated with an adverse prognosis. Citation Format: Marjanka K. Schmidt, Qi Guo, Thilo Dörk, Diana Eccles, Renske Keeman, Jacques Simard, Peter Kraft, Douglas F. Easton, Paul D. Pharoah, on behalf of the Breast Cancer Association Consortium. Genome-wide association studies of breast cancer prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2258. doi:10.1158/1538-7445.AM2017-2258
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».