Genetic Variation in Myeloperoxidase Modifies the Association of Serum a-Tocopherol with Aggressive Prostate Cancer among Current Smokers  

Oleh:

Cheng, Ting-Yuan David ; Barnett, Matt J. ; Kristal, Alan R.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 141 no. 09 (Sep. 2011), page 1731-1737 .
Topik: NUTRITIONAL EPIDEMIOLOGY

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2011.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

We investigated associations of serum a- and ?-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 a- and ?-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 a-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 a- and ?-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 a-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 a-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 a- and ?-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer. The a-tocopherol–associated risks are modified by polymorphism in MPO G–463A.

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