A Polymorphic Locus in the Promoter Region of the <i>IGFBP3</i> Gene Is Related to Mammographic Breast Density
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".