Source:http://linkedlifedata.com/resource/pubmed/id/16284371
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11 Pt 1
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| pubmed:dateCreated |
2005-11-14
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| pubmed:abstractText |
Folate metabolism supports the synthesis of nucleotides as well as the transfer of methyl groups. Polymorphisms in folate-metabolizing enzymes have been shown to affect risk of colorectal neoplasia and other malignancies. Using data from a population-based incident case-control study (1,600 cases and 1,962 controls), we investigated associations between genetic variants in the reduced folate carrier (RFC), thymidylate synthase (TS), methionine synthase (MTR), and 5,10-methylenetetrahydrofolate reductase (MTHFR) and colon cancer risk. The TS enhancer region (TSER) variant was associated with a reduced risk among men [2rpt/2rpt versus 3rpt/3rpt wild-type; odds ratio (OR), 0.7; 95% confidence interval, 0.6-0.98] but not women. When combined genotypes for both TS polymorphisms (TSER and 3'-untranslated region 1494delTTAAAG) were evaluated, ORs for variant genotypes were generally below 1.0, with statistically significantly reduced risks among women. Neither MTR D919G nor RFC 80G>A polymorphisms were associated with altered colon cancer risk. Because folate metabolism is characterized by interrelated reactions, we evaluated gene-gene interactions. Genotypes resulting in reduced MTHFR activity in conjunction with low TS expression were associated with a reduced risk of colon cancer. When dietary intakes were taken into account, individuals with at least one variant TSER allele (3rpt/2rpt or 2rpt/2rpt) were at reduced risk in the presence of a low folate intake. This study supports findings from adenoma studies indicating that purine synthesis may be a relevant biological mechanism linking folate metabolism to colon cancer risk. A pathway-based approach to data analysis is needed to help discern the independent and combined effects of dietary intakes and genetic variability in folate metabolism.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-Methyltetrahydrofolate-Homocystein...,
http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Reduced Folate Carrier Protein,
http://linkedlifedata.com/resource/pubmed/chemical/SLC19A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidylate Synthase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1055-9965
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
14
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2509-16
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:16284371-5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase,
pubmed-meshheading:16284371-Adenoma,
pubmed-meshheading:16284371-Adult,
pubmed-meshheading:16284371-Aged,
pubmed-meshheading:16284371-Case-Control Studies,
pubmed-meshheading:16284371-Colonic Neoplasms,
pubmed-meshheading:16284371-Diet,
pubmed-meshheading:16284371-Female,
pubmed-meshheading:16284371-Folic Acid,
pubmed-meshheading:16284371-Genetic Predisposition to Disease,
pubmed-meshheading:16284371-Genotype,
pubmed-meshheading:16284371-Humans,
pubmed-meshheading:16284371-Male,
pubmed-meshheading:16284371-Membrane Transport Proteins,
pubmed-meshheading:16284371-Middle Aged,
pubmed-meshheading:16284371-Odds Ratio,
pubmed-meshheading:16284371-Polymorphism, Genetic,
pubmed-meshheading:16284371-Reduced Folate Carrier Protein,
pubmed-meshheading:16284371-Thymidylate Synthase
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| pubmed:year |
2005
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| pubmed:articleTitle |
Polymorphisms in the reduced folate carrier, thymidylate synthase, or methionine synthase and risk of colon cancer.
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| pubmed:affiliation |
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402 Seattle, WA 98109-1024, USA. nulrich@fhcrc.org
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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