CYP11A1 Is a Predictor of Mammographic Breast Density.
Notice bibliographique
Résumé
Abstract Mammographic density (MD) is a strong predictor of breast cancer risk and is highly correlated with the hormone exposure profiles of women. It is also a highly heritable risk factor (heritable component ∼67%). As such, many efforts have been made to identify underlying genetic determinants of MD within pathways related to steroid hormone biosynthesis and metabolism. Several associations with genetic polymorphisms in genes involved in estrogen metabolism have been previously described (e.g. COMT and HSD3B1). Still, there is controversy among the conclusions of these studies. In addition, only a few candidate genes have been interrogated at a time. In this study, we assess associations of genetic variants with MD using the most extensive estrogen metabolic pathway coverage to date.Materials and methods:Cases were 891 Swedish-born women who were 50-74 years of age at diagnosis and diagnosed with breast cancer between October 1993 and March 1995. 840 controls were population and frequency matched to the expected age distribution of the cases.MD was measured using a computer-assisted technique (Cumulus, University of Toronto, Canada) and evaluated by comparing the dense area by the total breast area.Genotyping was performed on a total of 239 SNPs in 34 estrogen metabolic genes using the Sequenom (San Diego, California) primer extension-based assay. SNPs with a call rate <85%, minor allele frequency <1% or out of Hardy-Weinberg Equilibrium (p<0.05/239) were excluded from further analysis.The Cochran-Armitage trend test was carried out for all SNPs with adjustments for age, body mass index, menopausal status and hormone replacement therapy usage.Results:We report a novel association finding between MD and the gene CYP11A1. 5 out of 6 SNPs within the gene were found to be significant after adjustment. The average increase in MD attributed to these SNPs is 5.4%. Other genes with significant associations include HSD17B3, STS, and NQO1.Discussion:A high level of endogenous estrogen is well-known to be correlated with an increased risk of breast cancer. CYP11A1 encodes a member of the cytochrome P450 superfamily of enzymes and is of interest as it represents is the first as well as a rate-limiting step in steroid hormone biosynthesis.In addition, a role for CYP11A1 in the metabolism of vitamin D3 has been reported recently. High vitamin D levels have been associated with a decrease in both breast cancer risk and MD. Although the active compound most commonly implicated is 1,25-dihydroxyvitamin D3 derived from a more extensively studied pathway, new studies have shown that a by-product of CYP11A1 exhibits similar functions in the regulation of cell proliferation and differentiation.Although CYP11A1 has been previously reported to be associated with breast cancer, it has never been studied in relation to MD. This novel finding suggests that CYP11A1 exerts an influence on MD through two different pathways linked to breast cancer and affirms MD as an intermediate phenotype for the disease. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5161.
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 | 0,002 |
| 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) | 0,005 | 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 ».