BRCA1 mRNA levels following a 4–6-week intervention with oral 3,3′-diindolylmethane
Bibliographic record
Abstract
BACKGROUND: Haploinsufficiency may contribute to the development of breast cancer among women with a BRCA1 mutation. Thus, interventions that enhance BRCA1 expression may represent avenues for prevention. Studies have shown that 3,3'-diindolylmethane (DIM) can upregulate BRCA1 expression in breast cancer cells. This has yet to be demonstrated in vivo. METHODS: We conducted a study to evaluate the ability of oral DIM to upregulate BRCA1 mRNA expression in white blood cells. A total of 18 women were enroled in the study, including 13 BRCA1 mutation carriers who received 300 mg per day of Rx Balance BioResponse DIM for 4-6 weeks (intervention group) and 5 BRCA1 mutation carriers who did not take DIM (control group). BRCA1 mRNA expression was assessed at baseline and at 4-6 weeks by real-time, quantitative PCR and the relative change in BRCA1 mRNA expression (that is, 2(-ΔΔCT)) was calculated. RESULTS: The relative change in BRCA1 mRNA expression among women in the intervention group achieved borderline significance (P paired t-test=0.05). In the intervention group, BRCA1 mRNA expression increased in 10 of the participants, decreased in 2 and remained unchanged in 1 of the participants following DIM intervention (P sign test=0.02). On average, women in the intervention group experienced a 34% increase in BRCA1 mRNA expression (range -24 to 194%). There was no significant difference in the relative change in BRCA1 mRNA expression among women in the control group (P paired t-test=0.45). CONCLUSIONS: Under the tested conditions, oral DIM was associated with an increase in BRCA1 mRNA expression in women with a BRCA1 mutation. The possibility of mitigating the effect of an inherited deleterious BRCA1 mutation by increasing the physiologic expression of the gene and normalising protein levels represents a clinically important paradigm shift in the prevention strategies available to these high-risk women. Future studies with a larger sample size and higher doses of DIM are warranted.
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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) | 0.000 | 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".