Genetic variation in myeloperoxidase modifies the association of serum α-tocopherol with aggressive prostate cancer among current smokers

J Nutr. 2011 Sep;141(9):1731-7. doi: 10.3945/jn.111.141713. Epub 2011 Jul 27.


We investigated associations of serum α- and γ-tocopherols and their effect modification by polymorphisms in oxidative stress regulatory enzymes in relation to prostate cancer risk. In a nested case-control study in the Carotene and Retinol Efficacy Trial, prerandomized serum α- and γ-tocopherol were assayed among 684 men with incident prostate cancer [375 nonaggressive and 284 aggressive cancer (stage III/IV or Gleason score ≥7)] and 1441 controls. Manganese superoxide dismutase Ala-16Val (rs4880), glutathione peroxidase 1 Pro200Leu (rs1050450), catalase -262 C > T (rs1001179), and myeloperoxidase (MPO) G-463A (rs2333227) were genotyped. A multivariate-adjusted inverse association of serum α-tocopherol with total prostate cancer risk was observed in current smokers (OR = 0.62, 95% CI = 0.40-0.96, 4th vs. 1st quartiles). High (≥median) compared to low serum concentrations of α- and γ-tocopherol were inversely associated with aggressive prostate cancer in current smokers (OR = 0.50, 95% CI = 0.32-0.78 and OR = 0.64, 95% CI = 0.43-0.95, respectively). The association was stronger among those with MPO G/A+A/A genotypes. Among current smokers with low serum α-tocopherol concentrations, MPO G/A+A/A, the genotypes downregulating oxidative stress, were associated with an increased risk for aggressive prostate cancer (OR = 2.06, 95% CI = 1.22-3.46). Conversely, current smokers with these genotypes who had high α-tocopherol concentrations had a reduced risk for aggressive prostate cancer (OR = 0.34, 95% CI = 0.15-0.80; P-interaction = 0.001). In conclusion, among current smokers, both high serum α- and γ-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer. The α-tocopherol-associated risks are modified by polymorphism in MPO G-463A.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Case-Control Studies
  • Gene Expression Regulation, Enzymologic
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Oxidative Stress / genetics
  • Peroxidase / genetics
  • Peroxidase / metabolism*
  • Polymorphism, Genetic*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Smoking / blood*
  • alpha-Tocopherol / blood*
  • gamma-Tocopherol / blood


  • gamma-Tocopherol
  • Peroxidase
  • alpha-Tocopherol