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Research: CHENG and COLLEAGUES,
Listed in Issue 191
Abstract
CHENG and COLLEAGUES, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, Seattle, WA, USA investigated associations of serum alpha- and gamma-tocopherols and their effect modification by polymorphisms in oxidative stress regulatory enzymes in relation to prostate cancer risk.
Background
Methodology
In a nested case-control study in the Carotene and Retinol Efficacy Trial, prerandomized serum alpha- and gamma-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.
Results
A multivariate-adjusted inverse association of serum alpha-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 alpha- and gamma-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 alpha-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 alpha-tocopherol concentrations had a reduced risk for aggressive prostate cancer (OR = 0.34, 95% CI = 0.15-0.80; P-interaction = 0.001).
Conclusion
In conclusion, among current smokers, both high serum alpha- and gamma-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer. The alpha-tocopherol-associated risks are modified by polymorphism in MPO G-463A.
References
Cheng TY, Barnett MJ, Kristal AR, Ambrosone CB, King IB, Thornquist MD, Goodman GE and Neuhouser ML. Genetic variation in myeloperoxidase modifies the association of serum alpha-tocopherol with aggressive prostate cancer among current smokers. Journal of Nutrition. 141(9): 1731-7. Sep 2011.
