Abstract 4673: Host genetic polymorphisms at TIMP3 are associated with survival of patients with adenocarcinoma of esophagus and gastoeophageal junction
Notice bibliographique
Résumé
Abstract BACKGROUND: During the past two decades, several countries have experienced a dramatic increase in adenocarcinoma incidence for both the esophagus and gastroesophageal junction (GEJ). Because of this increase and generally poor survival, distal esophageal and GEJ adenocarcinomas are important in cancer research. Similarities and shared prognostic factors suggest these cancers can be considered a single neoplastic entity in many contexts. The American Joint Committee on Cancer (AJCC) Cancer Staging Manual uses “single-stage grouping” across the entire lower esophagus and GEJ area. The current study was conducted to examine the effect of polymorphism at TIMP and MMP genes as a host-related prognosis factor. METHODS: This study used a prospective cohort of patients with adenocarcinoma of the esophagus and GEJ in British Columbia (BC) admitted to the BC Cancer Agency (BCCA). Germline DNA was extracted from patients’ blood or saliva. Selected SNPs were genotyped using Sequenom multiplex iPLEX Gold assays. Patient characteristics and clinical information were obtained from BCCA medical charts and preadmission questionnaires. Cox proportional hazards regression was used to estimate the effect of SNPs adjusted for patient age, tumour location, disease stage and treatment received. P-values less than 0.05 were considered statistically significant. The false discovery rate (FDR) method was applied to address multiple comparisons. RESULTS: 4 genetic polymorphism at TIMP3 gene were associated with survival of patients. These associations were also observed after adjustment for patient age, tumour location, disease stage and treatment received. A SNP in the promoter region of TIMP3 (rs1962223) was associated with about a 3-fold increase in the HR for patients who carried the CG genotype. A tagSNP (rs130274) showed a more than 3-fold increased HR for the dominant and codominant models and 2-fold increased HR for the additive model. A tagSNP (rs715572) was associated with about a 3-fold increased HR for the dominant and codominant models and a 2-fold reduction in the HR for the additive model. Finally, a tagSNP (rs5754312) was associated with a 4-fold reduction in the HR in the recessive and codominant model, and a 2-fold reduction in the HR for the additive model, In haplotype analysis, a block including rs5754312 and rs715572 showed significant association with the patients’ survival (p=0.002). CONCLUSION: Adenocarcinoma of the esophagus and GEJ are deadly diseases that are often diagnosed at a stage when the treatment options are limited and have limited effectiveness. Modeling survival based on host factors including genetic polymorphisms is an emerging field in cancer research. Compared to tumour, the patient's constitutional genetic material is relatively easy to obtain, and can be assessed before treatment is started. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4673. doi:10.1158/1538-7445.AM2011-4673
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
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 ».