A Polymorphic Locus in the Promoter Region of the <i>IGFBP3</i> Gene Is Related to Mammographic Breast Density
Notice bibliographique
Résumé
BACKGROUND: Mammographic breast density is a significant risk factor for breast cancer. Women with dense tissue accounting for more than 60-75% of the area of the breast have a 4- to 6-fold increase in their risk of breast cancer, compared to women with little or no breast density. A high circulating level of insulin-like growth factor-I (IGF-I) and low IGF binding protein 3 (IGFBP-3) level have been associated with increased breast density in premenopausal women. Genetic polymorphisms in the IGF1 and IGFBP3 genes may influence breast and serum levels of these growth factors. The aims of this study were to determine whether polymorphic variations in the IGF1 and IGFBP3 genes are associated with breast density, and serum IGF-I and IGFBP-3 levels, and whether serum IGF-I and IGFBP-3 levels are associated with mammographic density. METHODS: A total of 441 white women, recruited from Women's College Hospital (Toronto, Ontario), enrolled in this study. Each woman completed a questionnaire, detailing information on age, menstrual history, hormone use, diet, and medical and mammography history. Blood samples were taken for DNA extraction to genotype the subjects for polymorphic variants in the two candidate genes, and for measurement of circulating levels of IGF-I and IGFBP-3. Mammographic films were retrieved from Women's College Hospital and digitized using a laser film scanner. The digitized images were assessed for breast density using a computer-assisted method. RESULTS: There was a positive association between serum IGFBP-3 levels and the number of A alleles at a previously described polymorphic locus in the promoter region of the IGFBP3 gene among premenopausal women (P = 0.01). There was also a positive trend in the mean percentage of breast density by the number of A alleles of the IGFBP3 gene among premenopausal women (P = 0.0005). Women with two A alleles had a 5-fold increase in the odds of having a percentage of breast density greater or equal to 28%, compared with women with no A allele (P = 0.002). However, there was no association between serum IGF-I and IGFBP-3 levels and breast density among premenopausal women (P > 0.05). CONCLUSIONS: This is the first study to report a strong relationship between a polymorphic gene locus (IGFBP3) and mammographic breast density. However, we could not confirm an association between serum IGF-I levels and breast density among premenopausal women, as demonstrated in previous studies.
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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 | 0,001 | 0,000 |
| 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) | 0,000 | 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.
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