title: Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial.
abstract: BACKGROUND
  Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.
  
  
  OBJECTIVE
  We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.
  
  
  METHODS
  Beginning in 1997, a total of 14,641 US male physicians aged ≥50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011.
  
  
  RESULTS
  This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions.
  
  
  CONCLUSIONS
  In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers.
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: Howard D
authors.initials: HD
authors.lastname: Sesso
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: William G
authors.initials: WG
authors.lastname: Christen
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: Vadim
authors.initials: V
authors.lastname: Bubes
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: From the Divisions of Preventive Medicine (LW, HDS, RJG, WGC, VB, JEM, JEB, and JMG), Aging (HDS and JMG), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (JMG); the Department of Ambulatory Care and Prevention Harvard Medical School, Boston, MA (JEB); and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (JEM and JEB).
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005500:Follow-Up Studies; D015994:Incidence; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D010820:Physicians; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014810:Vitamin E / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D014810:Vitamin E