Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial.
BACKGROUND
Soy isoflavones have numerous biological properties that suggest that they may protect against colorectal cancer. Colorectal epithelial cell proliferation has been used extensively as an intermediate endpoint biomarker for colorectal neoplasia.


OBJECTIVE
We tested the hypothesis that supplementation with soy protein containing isoflavones decreases colorectal epithelial cell proliferation.


METHODS
A 12-mo randomized intervention was conducted in men and women aged 50-80 y with recently diagnosed adenomatous polyps. One hundred fifty participants were enrolled and randomly assigned to an active treatment group (58 g protein powder/d containing 83 mg isoflavones/d; +ISO) or a control group (ethanol-extracted soy-protein powder containing 3 mg isoflavones; -ISO). Biopsy specimens from the cecum, sigmoid colon, and rectum were collected at baseline and at the 12-mo follow-up. Ki-67 antibody immunohistostaining was used to detect cell proliferation. One hundred twenty-five participants completed the study, and proliferation was measured in the first 91 who completed the study.


RESULTS
In the sigmoid colon, cell proliferation increased by 0.9 (95% CI: 0.09, 1.9) labeled nuclei per crypt more (11%) in the +ISO group than in the -ISO group over the 12-mo intervention, which was opposite the direction predicted. The number of labeled nuclei per 100 mum crypt height also increased more in the +ISO than in the -ISO group. In the cecum and sigmoid colon, but not in the rectum, the proliferation count increased as the serum genistein concentration increased. Proliferation distribution and crypt height were not changed by treatment at any site.


CONCLUSIONS
Supplementation with soy protein containing isoflavones does not reduce colorectal epithelial cell proliferation or the average height of proliferating cells in the cecum, sigmoid colon, and rectum and increases cell proliferation measures in the sigmoid colon.
Adams
Kenneth F
KF
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lampe
Paul D
PD
Newton
Katherine M
KM
Ylvisaker
J Thomas
JT
Feld
Andrew
A
Myerson
David
D
Emerson
Scott S
SS
White
Emily
E
Potter
John D
JD
Lampe
Johanna W
JW
D018256:Adenomatous Polyps / Q000178:diet therapy; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000473:pathology; D003111:Colonic Polyps / Q000178:diet therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007529:Isoflavones / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000166:cytology / Q000473:pathology; D030262:Soybean Proteins / Q000737:chemistry*
D007529:Isoflavones; D019394:Ki-67 Antigen; D030262:Soybean Proteins