Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-3-16
pubmed:abstractText
Genetic variation in the uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) enzyme is associated with impaired metabolism of aspirin. To determine whether polymorphisms in the UGT1A6 enzyme modulate the protective benefit of regular aspirin use on colorectal adenoma, we conducted a prospective, nested case-control study of 1062 women who provided blood specimens and detailed data on aspirin use before undergoing lower endoscopy. All statistical tests were two sided. Although UGT1A6 genotype was not associated with overall adenoma risk (multivariable odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.85 to 1.41), functional variant genotypes statistically significantly modified the effect of aspirin on adenoma (P(interaction) = .02). Among the 616 women with variant genotypes, regular use of aspirin (two or more standard tablets per week) was associated with a decreased risk of adenoma (multivariable OR for adenoma = 0.66 [95% CI = 0.45 to 0.95], OR = 0.63 [95% CI = 0.43 to 0.91] for 0.5-7 standard tablets per week and OR = 0.41 [95% CI = 0.24 to 0.71] for more than 7 tablets per week; P(trend) = .001). In contrast, among women with wild-type genotypes, regular aspirin use was not associated with a reduced risk nor did they obtain any additional benefit with higher doses (P(trend) = .50). These results were consistent among women with advanced adenomas (P(interaction) = .003). Thus, functional polymorphisms in the UGT1A6 enzyme statistically significantly modify the effect of aspirin on colorectal neoplasia, and certain subsets of the population, defined by genotype, may obtain differential benefit from aspirin chemoprevention.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1460-2105
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
457-60
pubmed:dateRevised
2011-5-19
pubmed:meshHeading
pubmed-meshheading:15770010-Adenoma, pubmed-meshheading:15770010-Aged, pubmed-meshheading:15770010-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:15770010-Aspirin, pubmed-meshheading:15770010-Case-Control Studies, pubmed-meshheading:15770010-Colonoscopy, pubmed-meshheading:15770010-Colorectal Neoplasms, pubmed-meshheading:15770010-Confidence Intervals, pubmed-meshheading:15770010-Confounding Factors (Epidemiology), pubmed-meshheading:15770010-Female, pubmed-meshheading:15770010-Glucuronosyltransferase, pubmed-meshheading:15770010-Humans, pubmed-meshheading:15770010-Incidence, pubmed-meshheading:15770010-Middle Aged, pubmed-meshheading:15770010-Odds Ratio, pubmed-meshheading:15770010-Polymorphism, Genetic, pubmed-meshheading:15770010-Prospective Studies, pubmed-meshheading:15770010-Risk Assessment, pubmed-meshheading:15770010-United States
pubmed:year
2005
pubmed:articleTitle
Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma.
pubmed:affiliation
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, GRJ-722, Boston, MA 02114, USA. achan@partners.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't