title: Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: results of a randomized trial.
abstract: BACKGROUND
  In two large, randomized prevention trials, supplementation with beta-carotene increased the risk of lung cancer. Subjects in these studies were predominantly cigarette smokers, and the adverse effects were concentrated among those who also drank alcohol. Although beta-carotene supplementation appeared not to increase the risk of cancer generally, it is not clear if smoking and/or alcohol use alters the effect of beta-carotene on carcinogenesis at sites outside the lung.
  
  
  METHODS
  We studied the effect of beta-carotene supplementation on colorectal adenoma recurrence among subjects in a multicenter double-blind, placebo-controlled clinical trial of antioxidants for the prevention of colorectal adenomas. A total of 864 subjects who had had an adenoma removed and were polyp-free were randomly assigned (in a factorial design) to receive beta-carotene (25 mg or placebo) and/or vitamins C and E in combination (1000 mg and 400 mg, respectively, or placebo), and were followed with colonoscopy for adenoma recurrence 1 year and 4 years after the qualifying endoscopy. A total of 707 subjects had two follow-up examinations and provided smoking and alcohol use data. Adjusted multivariate risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the effects of beta-carotene on adenoma recurrence.
  
  
  RESULTS
  Among subjects who neither smoked cigarettes nor drank alcohol, beta-carotene was associated with a marked decrease in the risk of one or more recurrent adenomas (RR = 0.56, 95% CI = 0.35 to 0.89), but beta-carotene supplementation conferred a modest increase in the risk of recurrence among those who smoked (RR = 1.36, 95% CI = 0.70 to 2.62) or drank (RR = 1.13, 95% CI = 0.89 to 1.43). For participants who smoked cigarettes and also drank more than one alcoholic drink per day, beta-carotene doubled the risk of adenoma recurrence (RR = 2.07, 95% CI = 1.39 to 3.08; P for difference from nonsmoker/nondrinker RR <.001).
  
  
  CONCLUSIONS
  Alcohol intake and cigarette smoking appear to modify the effect of beta-carotene supplementation on the risk of colorectal adenoma recurrence.
authors.affiliation: Department of Medicine, Dartmouth Medical School, , Evergreen Center, Lebanon, NH 03766, USA. john.a.baron@dartmouth.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Leila
authors.initials: L
authors.lastname: Mott
authors.forename: Robert
authors.initials: R
authors.lastname: Haile
authors.forename: Maria
authors.initials: M
authors.lastname: Grau
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Church
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Beck
authors.forename: E Robert
authors.initials: ER
authors.lastname: Greenberg
mesh_terms: D000236:Adenoma / Q000139:chemically induced* / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects; D016896:Treatment Outcome; D019207:beta Carotene / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D019207:beta Carotene