title: A randomized, placebo-controlled, preoperative trial of allopurinol in subjects with colorectal adenoma.
abstract: Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.
authors.affiliation: Office of the Scientific Director, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Branchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Argusti
authors.forename: Silvia
authors.initials: S
authors.lastname: Zanardi
authors.forename: Cristiano
authors.initials: C
authors.lastname: Crosta
authors.forename: Emanuele
authors.initials: E
authors.lastname: Meroni
authors.forename: Francesco
authors.initials: F
authors.lastname: Munizzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Michetti
authors.forename: Gianni
authors.initials: G
authors.lastname: Coccia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Roberto
authors.forename: Roberto
authors.initials: R
authors.lastname: Bandelloni
authors.forename: Laura
authors.initials: L
authors.lastname: Turbino
authors.forename: Egle
authors.initials: E
authors.lastname: Minetti
authors.forename: Marco
authors.initials: M
authors.lastname: Mori
authors.forename: Sandra
authors.initials: S
authors.lastname: Salvi
authors.forename: Simona
authors.initials: S
authors.lastname: Boccardo
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gatteschi
authors.forename: Roberto
authors.initials: R
authors.lastname: Benelli
authors.forename: Angelica
authors.initials: A
authors.lastname: Sonzogni
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000601:surgery*; D018256:Adenomatous Polyps / Q000188:drug therapy / Q000601:surgery; D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011300:Preoperative Care; D057234:Preoperative Period
chemical_list: D000964:Antimetabolites, Antineoplastic; D010919:Placebos; D000493:Allopurinol