title: Serum phospholipid fatty acids, genetic variation in myeloperoxidase, and prostate cancer risk in heavy smokers: a gene-nutrient interaction in the carotene and retinol efficacy trial.
abstract: The authors investigated associations of serum phospholipid n-3 and n-6 polyunsaturated fatty acids (PUFAs) and trans-fatty acids with prostate cancer risk, and whether myeloperoxidase G-463A (rs2333227) modified the associations in the Carotene and Retinol Efficacy Trial (CARET) (Seattle, Washington; Irvine, California; New Haven, Connecticut; San Francisco, California; Baltimore, Maryland; and Portland, Oregon, 1985-2003). Prerandomization sera were assayed for fatty acids among 641 men with incident prostate cancer (368 nonaggressive and 273 aggressive (stage III/IV or Gleason score ≥7)) and 1,398 controls. Overall, dihomo-γ-linolenic (quartiles 4 vs. 1: odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.49, 0.95; P(trend) = 0.024) and docosatetraenoic (OR = 0.69, 95% CI: 0.46, 1.02; P(trend) = 0.011) acids were inversely associated with nonaggressive and aggressive prostate cancer risks, respectively. Among men with MPO GG, the genotype upregulating oxidative stress, quartiles 4 versus 1 eicosapentaenoic plus docosahexaenoic acids were suggestively associated with an increased risk of aggressive prostate cancer (OR = 1.66, 95% CI: 0.95, 2.92; P(trend) = 0.07). However, the association was the inverse among men with MPO GA/AA genotypes (P(interaction) = 0.011). Interactions were also observed for docosapentaenoic acid, total n-3 PUFAs, and arachidonic acid. MPO GA/AA vs. GG was associated with a 2-fold increase in aggressive prostate cancer risk among men with low (quartile 1) n-3 PUFAs. This study adds important evidence linking oxidative stress with prostate carcinogenesis.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4B402, Seattle, WA 98109-1024, USA. tcheng@fhcrc.org
authors.forename: Ting-Yuan David
authors.initials: TY
authors.lastname: Cheng
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Mark D
authors.initials: MD
authors.lastname: Thornquist
authors.forename: Gary E
authors.initials: GE
authors.lastname: Goodman
authors.forename: Marian L
authors.initials: ML
authors.lastname: Neuhouser
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D005231:Fatty Acids, Unsaturated; D009195:Peroxidase
keywords: gene-environment interaction; myeloperoxidase; polyunsaturated fatty acids; prostate cancer; trans-fatty acids
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