Abstract 3110: Shorter naïve T cell telomere length is associated with thyroid subsequent malignant neoplasm: A report from the Childhood Cancer Survivor Study (CCSS)
Notice bibliographique
Résumé
Abstract Introduction: Reduced blood telomere content has been associated with an increased risk for subsequent malignant neoplasms of the thyroid (thyroid SMN) in survivors of childhood cancer (PMID 24277454). Here, we further investigate this association by examining telomere length (TL) in leukocyte subsets. Methods: Survivors were enrolled to the CCSS, a multicenter, retrospective cohort of 5-year + survivors of childhood cancer. Cases were survivors with thyroid SMN, and matched (1:1) to survivor controls without SMN by primary diagnosis, year of primary diagnosis (decade), chemotherapy (yes/no), radiation field, and follow-up time (exceeding time to SMN for the case). Stem cell transplant recipients were excluded. Absolute TL was determined from viably frozen leukocytes (lymphocytes, naïve T, memory T, B, and NK cells) by telomere flow cytometry fluorescence in situ hybridization (telomere flow FISH, Repeat Diagnostics), and transformed to age-adjusted percentiles based on age at sample collection. For each leukocyte subset, we used McNemar’s test to compare frequency of very low (VL, ≤1st age-adjusted percentile) or low (L, >1st to ≤10th percentile), and a paired t-test to compare age-adjusted TL between cases and controls. Odds ratios were determined by conditional logistic regression. Results: Of the 52 matched pairs identified, 46 pairs (92 survivors) had sufficient cell recovery for flow FISH: primary diagnoses included Hodgkin lymphoma (20 pairs), acute lymphoblastic leukemia (13 pairs), CNS tumors (7 pairs), neuroblastoma (2 pairs), non-Hodgkin lymphoma (3 pairs), and kidney tumor (1 pair). All survivors had age-adjusted TL below the population median. Cases had shorter age-adjusted TL than controls in 4 out of 5 leukocyte subsets: lymphocytes (p=0.04), naïve T cells (p=0.02), B cells (p=0.01), and NK cells (p=0.01). Naïve T cells had an overrepresentation of VL TL (cases with VL TL in 9/46 pairs vs. controls with VL TL in 2/46 pairs, p=0.04). The odds of L or VL naïve T cell TL was significantly higher in cases compared with controls (OR=2.8, 1.11-7.19, p=0.03), an observation that did not change after adjusting for age at diagnosis. Conclusions: Survivors of childhood cancer had shorter age-adjusted leukocyte TL than the general population. This negative deviation was more pronounced among survivors with thyroid SMN than in survivors without SMN, which may reflect a differential risk among survivors for excess premature aging in the hematopoietic compartment. The effect of SMN treatment on TL is unlikely to be a factor, as treatment for thyroid SMN is primarily surgical. In cancer-naïve populations, VL lymphocyte TL is a sensitive and specific indicator of underlying defects in telomere maintenance. In survivors of childhood cancer, VL TL in naïve T cells may reflect an association between SMN risk and defects in T cell-mediated cancer surveillance. Citation Format: Maria M. Gramatges, Geraldine Aubert, Elmira Hariri, Yan Chen, John A. Whitton, Wendy M. Leisenring, Michael A. Arnold, Joseph P. Neglia, Yutaka Yasui, Leslie L. Robison, Gregory T. Armstrong, Smita Bhatia. Shorter naïve T cell telomere length is associated with thyroid subsequent malignant neoplasm: A report from the Childhood Cancer Survivor Study (CCSS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3110.
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 | 0,001 | 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) | 0,002 | 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 ».