title: BRCA1 mRNA levels following a 4-6-week intervention with oral 3,3'-diindolylmethane.
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.
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Kotsopoulos
authors.affiliation: Familial Breast Cancer Research Unit, Women's College Research Institute, Toronto, Ontario, M5G 1N8 Canada.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, M5T 2M9 Canada.
authors.forename: L
authors.initials: L
authors.lastname: Salmena
authors.affiliation: Familial Breast Cancer Research Unit, Women's College Research Institute, Toronto, Ontario, M5G 1N8 Canada.
authors.forename: M
authors.initials: M
authors.lastname: Llacuachaqui
authors.affiliation: BioResponse, LLC, Boulder, CO 80303, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zeligs
authors.affiliation: Familial Breast Cancer Research Unit, Women's College Research Institute, Toronto, Ontario, M5G 1N8 Canada.
authors.forename: P
authors.initials: P
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000517:prevention & control*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016588:Anticarcinogenic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D007211:Indoles; D012333:RNA, Messenger; C016392:3,3'-diindolylmethane