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Br J Cancer. 2014 Sep 23;111(7):1269-74. doi: 10.1038/bjc.2014.391. Epub 2014 Jul 15.

BRCA1 mRNA levels following a 4-6-week intervention with oral 3,3'-diindolylmethane.

Author information

1
1] Familial Breast Cancer Research Unit, Women's College Research Institute, Toronto, Ontario, M5G 1N8 Canada [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7 Canada.
2
Familial Breast Cancer Research Unit, Women's College Research Institute, Toronto, Ontario, M5G 1N8 Canada.
3
Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, M5T 2M9 Canada.
4
BioResponse, LLC, Boulder, CO 80303, USA.

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.

PMID:
25025957
PMCID:
PMC4183839
DOI:
10.1038/bjc.2014.391
[Indexed for MEDLINE]
Free PMC Article

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