title: Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial.
abstract: BACKGROUND
  Although smoking and alcohol consumption are the major risk factors for upper aerodigestive tract cancers, observational studies indicate a protective role for fruits, vegetables, and antioxidant nutrients.
  
  
  METHODS
  The authors examined whether daily supplementation with 50 mg dl alpha-tocopheryl acetate and/or 20 mg beta-carotene reduced the incidence of or mortality from oral/pharyngeal, esophageal, and laryngeal cancers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a double-blind, placebo-controlled primary prevention trial conducted in southwestern Finland. A total of 29,133 male smokers, aged 50-69 years and free of cancer at baseline, were randomized in a 2 x 2 factorial design to the supplementation regimen for 5-8 years (median, 6.1 years). Incident cancers of the oral cavity and pharynx (n = 65), esophagus (n = 24), and larynx (n = 56) were identified through the Finnish Cancer Registry. Intervention effects were assessed using survival analysis and proportional hazards models.
  
  
  RESULTS
  There was no effect of either agent on the overall incidence of any upper aerodigestive tract cancer. For larynx, however, exploratory subgroup analyses were suggestive of a protective effect of beta-carotene supplementation on the incidence of early stage malignancies (stage I, relative risk [RR], 0.28, 95% confidence interval [CI]: 0.10-0.75). Neither agent affected mortality from these neoplasms.
  
  
  CONCLUSIONS
  The results do not provide support for a protective effect of vitamin E or beta-carotene supplementation on upper aerodigestive tract cancers, although beta-carotene supplementation may impact the incidence of some subtypes of laryngeal tumors.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA. mewright@uic.ed
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Wright
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hartman
authors.forename: Pirjo
authors.initials: P
authors.lastname: Pietinen
authors.forename: Brenda K
authors.initials: BK
authors.lastname: Edwards
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Jussi K
authors.initials: JK
authors.lastname: Huttunen
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
mesh_terms: D000368:Aged; D019587:Dietary Supplements; D004311:Double-Blind Method; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention; D012907:Smoking / Q000009:adverse effects; D014815:Vitamins / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000627:therapeutic use*; D019207:beta Carotene / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D019207:beta Carotene; D024502:alpha-Tocopherol