Linked Life Data

21504893

Source:http://linkedlifedata.com/resource/pubmed/id/21504893

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-6-3
pubmed:abstractText
DNA damage is thought to play a critical role in the development of colorectal adenoma. Variation in DNA repair genes may alter their capacity to correct endogenous and exogenous DNA damage. We explored the association between common single-nucleotide polymorphisms (SNPs) in DNA repair genes and adenoma risk with a case-control study nested in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 1338 left sided, advanced colorectal adenoma cases and 1503 matched controls free of left-sided polyps were included in the study. Using DNA extracted from blood, 3144 tag SNPs in 149 DNA repair genes were successfully genotyped. Among Caucasians, 30 SNPs were associated with adenoma risk at P < 0.01, with four SNPs remaining significant after gene-based adjustment for multiple testing. The most significant finding was for a non-synonymous SNP (rs9350) in Exonuclease-1 (EXO1) [odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.11-1.51, P = 0.001)], which was predicted to be damaging using bioinformatics methods. However, the association was limited to smokers with a strong risk for current smokers (OR = 2.15, 95% CI = 1.27-3.65) and an intermediate risk for former smokers (OR = 1.45, 95% CI = 1.14-1.82) and no association for never smokers (OR = 0.98, 95% CI = 0.76-1.25) (P(interaction) = 0.002). Among the top findings, an SNP (rs17503908) in ataxia telangiectasia mutated (ATM) was inversely related to adenoma risk (OR = 0.75, 95% CI = 0.63-0.91). The association was restricted to never smokers (OR = 0.55, 95% CI = 0.40-0.76) with no increased risk observed among smokers (OR = 0.89, 95% CI = 0.70-1.13) (P(interaction) = 0.006). This large comprehensive study, which evaluated all presently known DNA repair genes, suggests that polymorphisms in EXO1 and ATM may be associated with risk for advanced colorectal adenoma with the associations modified by tobacco-smoking status.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
882-7
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:21504893-Adenoma, pubmed-meshheading:21504893-Aged, pubmed-meshheading:21504893-Case-Control Studies, pubmed-meshheading:21504893-Cell Cycle Proteins, pubmed-meshheading:21504893-Colorectal Neoplasms, pubmed-meshheading:21504893-DNA Repair, pubmed-meshheading:21504893-DNA-Binding Proteins, pubmed-meshheading:21504893-Deoxyribonucleases, pubmed-meshheading:21504893-Female, pubmed-meshheading:21504893-Genetic Markers, pubmed-meshheading:21504893-Genetic Predisposition to Disease, pubmed-meshheading:21504893-Genotype, pubmed-meshheading:21504893-Humans, pubmed-meshheading:21504893-Male, pubmed-meshheading:21504893-Middle Aged, pubmed-meshheading:21504893-Polymorphism, Single Nucleotide, pubmed-meshheading:21504893-Prognosis, pubmed-meshheading:21504893-Protein-Serine-Threonine Kinases, pubmed-meshheading:21504893-Risk Factors, pubmed-meshheading:21504893-Smoking, pubmed-meshheading:21504893-Tumor Suppressor Proteins
pubmed:year
2011
pubmed:articleTitle
DNA repair gene polymorphisms and tobacco smoking in the risk for colorectal adenomas.
pubmed:affiliation
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7236, USA. gaoying@mail.nih.gov
pubmed:publicationType
Journal Article, Comparative Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural