| Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat. | |
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MedLine Citation:
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PMID: 21037106 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. METHODS: Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). RESULTS: Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). CONCLUSIONS: We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. IMPACT: Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. |
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Authors:
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Asgeir Brevik; Amit D Joshi; Román Corral; N Charlotte Onland-Moret; Kimberly D Siegmund; Loïc Le Marchand; John A Baron; Maria Elena Martinez; Robert W Haile; Dennis J Ahnen; Robert S Sandler; Peter Lance; Mariana C Stern |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-29 |
Journal Detail:
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Title: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Volume: 19 ISSN: 1538-7755 ISO Abbreviation: Cancer Epidemiol. Biomarkers Prev. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-15 Completed Date: 2011-04-06 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 9200608 Medline TA: Cancer Epidemiol Biomarkers Prev Country: United States |
Other Details:
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Languages: eng Pagination: 3167-73 Citation Subset: IM |
Copyright Information:
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©2010 AACR. |
Affiliation:
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Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, California 90089, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Case-Control Studies Colorectal Neoplasms / genetics* DNA Glycosylases / genetics DNA Repair / genetics* DNA Repair Enzymes / genetics DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics DNA-Binding Proteins / genetics Diet / adverse effects* Genotype Humans Meat / adverse effects* Odds Ratio Poly(ADP-ribose) Polymerases / genetics Polymorphism, Single Nucleotide* Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
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5P30 ES07048/ES/NIEHS NIH HHS; 5U01074799//PHS HHS; P30 ES007048-09/ES/NIEHS NIH HHS; U01 CA074799-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/X-ray repair cross complementing protein 1; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/oxoguanine glycosylase 1, human; EC 4.2.99.18/APEX1 protein, human; EC 4.2.99.18/DNA-(Apurinic or Apyrimidinic Site) Lyase; EC 6.5.1.-/DNA Repair Enzymes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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