GENETIC VARIATION AT THE INSULIN-LIKE GROWTH FACTOR 1 GENE AND ASSOCIATION WITH BREAST CANCER, BREAST DENSITY AND ANTHROPOMETRIC MEASURES
Bibliographic record
Abstract
Background and objectives \n \nEvidence suggests that circulating IGF-I levels increase mammographic density (a breast cancer risk factor) and breast cancer risk in premenopausal women. The objective of this thesis was to examine the association of genetic variation at the IGF1 gene with IGF-I concentration, mammographic density, breast cancer risk, and related anthropometric measures in premenopausal women. \n \nMethods \n \nThree IGF1 CA repeat polymorphisms (at the 5′ and 3′ ends, and in intron 2) were genotyped. A cross-sectional design was used to investigate their associations with IGF-I levels, mammographic density, BMI, weight, and height. Families from registries in Ontario and Australia were used to investigate associations with breast cancer risk and also BMI, weight and height. \nResults \nIn the cross-sectional study, greater number of copies of the 5′ 19 allele were associated with lower circulating IGF-I levels. Greater number of 3′ 185 alleles were associated with greater percentage breast density, smaller amount of non-dense tissue, and lower BMI. Including BMI in regression models removed the association of the 3′ 185 allele with percentage breast density. \nIn the family based study, nominally significant associations (5′ 21 allele, intron 2 212 allele, intron 2 216 allele) with breast cancer risk were observed, but significance was lost after multiple comparison adjustment. There was a stronger association between the intron 2 216 allele and risk under a recessive model, and 5′ allele groupings of length 18 to 20 and 20 or more repeats produced significant positive and negative associations respectively. These associations were not strongly supported in analyses stratified by registry. Results from the family based study did not support an association between genetic variation at IGF1 with BMI, weight or height. \n \nConclusions \n \nNo specific IGF1 variant influenced each of circulating IGF-I levels, mammographic density, and breast cancer risk. The failure to replicate the association of the 3′ 185 allele with BMI in the family based study suggests that the association of the 3′ 185 allele with percentage breast density is spurious, since this association was mediated through the relationship with BMI (suggesting IGF-I action on body fat). Evidence for an association between IGF1 and breast cancer risk was limited.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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".