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Carcinogenesis. 2014 Jun;35(6):1276-83. doi: 10.1093/carcin/bgu028. Epub 2014 Feb 17.

Dietary iron, iron homeostatic gene polymorphisms and the risk of advanced colorectal adenoma and cancer.

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School of Health and Rehabilitation Sciences, University of Pittsburgh, 4051 Forbes Tower, Pittsburgh, PA 15260, USA,
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Department of Epidemiology, School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Inc., Gaithersburg, MD 20892, USA.
Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.
University of Pittsburgh Medical Center Cancer Pavilion, Pittsburgh, PA 15232, USA and.
Yale School of Public Health, New Haven, CT 06520, USA.


Dietary iron intake and variation in iron homeostasis genes may affect colorectal neoplasia risk. We conducted two nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: one of advanced colorectal adenoma (1205 cases; 1387 controls) and one of colorectal cancer (370 cases; 401 controls). Iron intake was estimated with a food frequency questionnaire and genotyping was performed for 21 genes. Unconditional logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) for colorectal neoplasia risk within quartiles of intake. Several single nucleotide polymorphisms (SNPs) modified the association between iron intake and the risk of adenoma or cancer. Dietary iron was positively associated with colorectal adenoma among three SNPs of HEPHL1, including carriers of the AA genotype at rs7946162 (ORQ4-Q1 = 2.22, 95% CI 1.15-4.27, Ptrend = 0.03; Pinteraction = 0.10), the TT genotype at rs2460063 (ORQ4-Q1 = 2.39, 95% CI 1.26-4.54, Ptrend = 0.02; Pinteraction = 0.04) and the GG genotype at rs7127348 (ORQ4-Q1 = 2.40, 95% CI 1.23-4.67, Ptrend = 0.02; Pinteraction = 0.09). Heme iron was positively associated with colorectal cancer among those with GG genotypes for ACO1 rs10970985 (ORQ4-Q 1 = 2.45, 95% CI 3.40-8.06, Ptrend = 0.004; Pinteraction = 0.05). However, none of the associations were statistically significant after adjustment for multiple comparisons. Future studies should target the specific genes and SNPs for which the association was significant prior to multiple comparison correction.

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