Abstract 816: Genetic variants associated with C-reactive protein and colorectal cancer survival: Sex- and lifestyle factors- specific associations
Notice bibliographique
Résumé
Abstract Background: Elevated levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival and CRC prognostic factors, such as obesity, smoking, and alcohol consumption. However, the mechanisms underlying these associations are not well understood. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. Methods: This study included 16,142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium (ISACC). We identified 741 common single nucleotide polymorphisms (SNPs) associated with CRP (minor allele frequency >5% in European ancestry) from the NHGRI-EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for SNP-specific association with CRC-specific mortality adjusting for age, sex, genotyping platform/study, and the first three principal components of genetic ancestry. SNPs were examined using log-additive models. Likelihood ratio tests were used to investigate multiplicative gene-environment interactions between CRP-associated SNPs and sex, obesity, ever smoking, and alcohol consumption. We also conducted stratified analyses according to these factors. P values were adjusted using Bonferroni correction, with corrected P <0.05 considered statistically significant. Results: After a median of 4.7 years (interquartile range = 2.3 to 7.7 years) of follow-up since diagnosis, 5,472 (33.9%) deaths accrued, 3,547 (64.8%) of which were due to CRC. No variants were statistically significantly associated with CRC-specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC mortality (corrected Pinteraction = 0.0004); women had higher CRC-specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04 to 1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82 to 0.94). There was no evidence of statistically significant interactions between CRP-associated SNPs and alcohol, obesity or smoking in association with CRC-specific mortality. Conclusions: Our study observed a statistically significant interaction between sex and a CRP-associated variant in relation to CRC-specific mortality. Future replication of this association and functional annotation of the variant are needed. Citation Format: Yuhan Huang, Xinwei Hua, Julia D. Labadie, Tabitha A. Harrison, James Dai, Sara Lindstrom, Yi Lin, Sonja I. Berndt, Daniel D. Buchanan, Peter T. Campbell, Graham Casey, Steven J. Gallinger, Marc J. Gunter, Michael Hoffmeister, Mark A. Jenkins, Lori C. Sakoda, Robert E. Schoen, Brenda Diergaarde, Martha L. Slattery, Emily White, Roger Milne, Graham Giles, Andrew T. Chan, Ulrike Peters, Polly A. Newcomb. Genetic variants associated with C-reactive protein and colorectal cancer survival: Sex- and lifestyle factors- specific associations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 816.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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) | 0,005 | 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 ».