Linked Life Data

20403997

Source:http://linkedlifedata.com/resource/pubmed/id/20403997

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-5-6
pubmed:abstractText
Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol synthesis, modifies the effect of statins on serum cholesterol levels. Long-term use of statins is associated with a reduced risk of colorectal cancer (CRC) in some, but not all, studies. We genotyped variants in 40 candidate genes important for cholesterol synthesis and metabolism in a population-based case-control study of CRC involving 2,138 incident cases and 2,049 population-based controls. We identified a single-nucleotide polymorphism in the HMGCR gene that significantly modified the protective association between statins and CRC risk. Compared with nonusers, the unadjusted odds ratio of CRC among statin users with the A/A genotype of rs12654264 in HMGCR was 0.3 (95% confidence interval, 0.18-0.51) and among statin users with the T/T genotype was 0.66 (95% confidence interval, 0.41-1.06; P-interaction = 0.0012). This genetic variant (A/A genotype of rs12654264) also was associated with lower serum levels of low-density lipoprotein among all cases and controls. In colon cancer cell lines, the reduction in cholesterol levels after statin treatment was substantially stronger in cells carrying the A/A genotype, and this difference was related to alternative splicing involving the HMGCR statin-binding domain. We anticipate that these data may advance the development of personalized statin use for reducing the risk of cancer as well as cardiovascular disease among the approximately 25 million people currently using statins worldwide.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1940-6215
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
597-603
pubmed:dateRevised
2010-9-16
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer.
pubmed:affiliation
Department of Medicine, Weill Cornell School of Medicine, New York, New York 10021, USA. stl2012@med.cornell.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural