Carcinogenesis Advance Access originally published online on February 22, 2008
Carcinogenesis 2008 29(5):964-970; doi:10.1093/carcin/bgn056
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Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA
1 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
* To whom correspondence should be addressed. Tel: +1 716 845 1350; Fax: +1 716 845 8125; Email: christine.ambrosone{at}roswellpark.org
Iron overload may increase prostate cancer risk through stimulation of oxidative stress, and endogenous pro- and antioxidant capabilities, i.e. manganese superoxide dismutase (MnSOD) and myeloperoxidase (MPO), may modify these associations. We investigated this hypothesis in the Carotene and Retinol Efficacy Trial cohort in a nested case–control study. Although there was no association between iron intake and risk overall, there was a suggestion of increased risk of clinically aggressive prostate cancer with higher iron intake [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 0.9–2.0]. Associations were most notable for men with aggressive prostate cancer who were below the median consumption of total fruits and vegetables (OR = 1.8, 95% CI = 1.1–3.2). Associations between MPO –463 G to A genotype (rs2333227) and prostate cancer risk were only noted among men with aggressive cancer, with more than a 2-fold risk reduction among men with AA genotypes (OR = 0.4, 95% CI = 0.2–1.0); MnSOD was not associated with risk overall, but the MnSOD T to C (Val-9Ala, rs4880) polymorphism modified associations between risk of clinically aggressive prostate cancer and dietary iron intake (P for interaction = 0.02). Among aggressive cancer cases with the TT genotype, higher iron intake level was associated with >2-fold increase in risk (OR = 2.3, 95% CI = 1.0–4.9), whereas there was no association among men with CC genotypes (OR = 0.9, 95% CI = 0.4–2.3). Although interactions were not significant, there were similar patterns for MPO genotype, iron intake and risk. These findings suggest that higher iron intake may be associated with risk of clinically aggressive prostate cancer, and that endogenous antioxidant capabilities may modify these associations.
Abbreviations: BMI, body mass index; CARET, Carotene and Retinol Efficacy Trial; CI, confidence interval; FDR, false discovery rate; FFQ, food frequency questionnaire; MnSOD, manganese superoxide dismutase; MPO, myeloperoxidase; OR, odds ratio; ROS, reactive oxygen species
Received October 22, 2007; revised January 22, 2008; accepted February 15, 2008.
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