Abstract A09: The relationship between DNA methylation in one-carbon metabolism genes and colorectal adenoma risk
Notice bibliographique
Résumé
Abstract Background: The one-carbon (1C) metabolism cycle consists of a network of interrelated biochemical reactions that provide 1C units required for critical intracellular processes. Polymorphisms in MTHFR and DMNT3b, genes central to the 1C metabolism cycle, and colorectal cancer risk have been reported. Variation in the expression of genes may be attributable to functional polymorphisms; but, it is increasingly clear that epigenetic variation also affects gene expression. DNA methylation, which involves the covalent addition of a methyl group to cytosine residues that precede guanine (CpG), is the most commonly studied epigenetic mechanism. This research investigated the relationship between DNA methylation in the MTHFR and DNMT3b genes, and colorectal adenoma risk; higher methylation was hypothesized to decrease gene expression and contribute to colorectal adenoma risk. Methods: A cross-sectional study recruited 272 patients aged 40-65 undergoing a screening colonoscopy. DNA methylation in the MTHFR and DNMT3b genes was quantified in DNA isolated from blood leukocytes using the Sequenom EpiTYPER® technology. Genomic regions of interest of each gene were selected based on location of CpG islands (1000-2000 base pairs) around the transcriptional start site. Raw data consisted of methylation ratios for 53 and 82 CpG units (a unit consists of either an individual CpG site or aggregates of multiple CpG sites) for MTHFR and DNMT3b, respectively; methylation ratio equals the percentage of methylated cytosines at a specific CpG unit of a gene, divided by the total number of copies of that CpG unit in the sample. Methylation data was cleaned to remove CpG units with potentially unreliable methylation ratios and those with little variability (SD<0.02). After data cleaning, a total of 14 MTHFR and 43 DNMT3b CpG units remained. For CpG units with missing values, the mean of each unit was assigned (occurred <11.4% of units); only participants with data for greater than 90% of the CpG units were included in this study yielding a total of 260 participants. Logistic regression was used to examine relationships between DNA methylation in MTHFR and DNMT3b on colorectal adenoma risk in separate sex- and age-adjusted models. Gene-specific DNA methylation for MTHFR and DNMT3b was conceptualized using two approaches: 1) a composite measure representing average methylation across all CpG units and; 2) unsupervised principal component (PC) analysis, a pattern derivation and data-reduction approach, to develop a smaller number of PCs which account for most of the variance in the methylation of CpG units. Composite and PC measures were categorized using equal-distant cut-points. Results: In our study population of 86 patients with colorectal adenoma and 174 patients with normal colonoscopies, no associations were observed between overall average DNA methylation in MTHFR or DNMT3b, and colorectal adenoma risk. Using unsupervised PC analysis, 3 PCs were derived accounting for 42% and 54% of the variance in the CpG units of MTHFR and DNMT3b, respectively. No association was observed in PC analysis for MTHFR. For DNMT3b, a higher score in PC1 was associated with colorectal adenoma risk (p=0.02); specifically, CpG units approximately 250 base pairs 5' and 3' of the transcriptional start site were found to load heavily onto PC1and higher methylation in this region was found to be associated with colorectal adenoma risk (OR=4.01 (95% CI: 1.17-13.78) when contrasting the highest versus lowest category of methylation). Conclusion: DNMT3b plays an important role in establishing and maintaining methylation patterns. Results of this novel investigation of epigenetic changes in 1C metabolism genes and colorectal adenoma risk suggest that alterations in methylation of the DNMT3b gene may be relevant to colorectal cancer etiology. Citation Format: Vikki Ho, Janet A. Ashbury, Sherryl Taylor, Stephen Vanner, Will D. King. The relationship between DNA methylation in one-carbon metabolism genes and colorectal adenoma risk. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A09.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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) | 0,000 | 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 tête enseignante, 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 ».