A phase Ib study of the effects of black raspberries on rectal polyps in patients with familial adenomatous polyposis.
Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P = 0.036) but not number (P = 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP.
Authors' Affiliations: Division of Hematology and Oncology, Department of Medicine;
Li-Shu
LS
Wang
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland;
Carol A
CA
Burke
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland;
Henrietta
H
Hasson
Authors' Affiliations: Division of Hematology and Oncology, Department of Medicine;
Chieh-Ti
CT
Kuo
Department of Epidemiology, Columbia University, New York, New York; and.
Christine L Sardo
CL
Molmenti
Comprehensive Cancer Center;
Claire
C
Seguin
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Pengyuan
P
Liu
Department of Molecular Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, Texas.
Tim H-M
TH
Huang
Department of Pathology, Ohio State University, Columbus, Ohio;
Wendy L
WL
Frankel
Authors' Affiliations: Division of Hematology and Oncology, Department of Medicine; gstoner@mcw.edu.
Gary D
GD
Stoner
D000236:Adenoma / Q000473:pathology / Q000517:prevention & control*; D011125:Adenomatous Polyposis Coli / Q000473:pathology / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D005638:Fruit; D006801:Humans; D008297:Male; D008875:Middle Aged; D011127:Polyps / Q000473:pathology*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012007:Rectum / Q000187:drug effects* / Q000473:pathology; D065856:Rubus / Q000737:chemistry*