Genetic Variation in Myeloperoxidase Modifies the ... [J Nutr. 2011] - PubMed result

Genetic Variation in Myeloperoxidase Modifies the ... [J Nutr. 2011] - PubMed result: "J Nutr. 2011 Jul 27. [Epub ahead of print]
Genetic Variation in Myeloperoxidase Modifies the Association of Serum {alpha}-Tocopherol with Aggressive Prostate Cancer among Current Smokers.
Cheng TY, Barnett MJ, Kristal AR, Ambrosone CB, King IB, Thornquist MD, Goodman GE, Neuhouser ML.

Source

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, Seattle, WA.

Abstract

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.

PMID:
21795425
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