Linked Life Data

17372271

Source:http://linkedlifedata.com/resource/pubmed/id/17372271

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-7-12
pubmed:abstractText
One-carbon metabolism facilitates the crosstalk between genetic and epigenetic processes and plays critical roles in both DNA methylation and DNA synthesis, making it a good candidate for studying the risk of breast cancer. We previously reported that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) in one-carbon pathway were associated with breast cancer risk in the population-based Long Island Breast Cancer Study Project. Herein, we systematically investigated putatively functional polymorphisms of seven other one-carbon-metabolizing genes in relation to the breast cancer risk in the same population. Except for a slight indication of increased risk of breast cancer associated with the double repeat (2R) allele in the thymidylate synthase (TYMS) 5'-untranslated region (UTR) (P, trend = 0.07), polymorphisms in the other six genes did not substantially modify the risk of breast cancer, or did they modify the risk associated with dietary intakes of folate and related B vitamins. However, we observed a significant multiplicative interaction between the MTHFR 677C>T and the TYMS 5'-UTR polymorphisms (P = 0.02). We used a recursive partitioning method, RTREE, in an attempt to tease out important or rate-limiting genes encoding these intricately related enzymes. Results from RTREE analyses indicate that MTHFR and TYMS are the two leading rate-limiting enzymes in the pathway, consistent with our epidemiological findings. Our findings underscore the importance of one-carbon metabolism in breast cancer etiology. Although the pathway is a network of interrelated enzymes, redundancy exists; evaluating the rate-limiting enzyme and its interaction with environment and other genes within the same pathway is critical in assessing breast cancer risk.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1504-9
pubmed:dateRevised
2007-12-20
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Polymorphisms of one-carbon-metabolizing genes and risk of breast cancer in a population-based study.
pubmed:affiliation
Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural