Source:http://linkedlifedata.com/resource/pubmed/id/11023538
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2000-11-1
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| pubmed:abstractText |
NAD(P)H:quinone oxidoreductase (NQO1) is a polymorphic enzyme involved in the detoxification of potentially mutagenic and carcinogenic quinones. The homozygous C609T NQO1 genotype resulting in loss of reductase activity is found in 2-20% of individuals. In the present study, the NQO1-dependent risk for sporadic colorectal cancer (CRC) was studied in 247 incident CRC cases and 296 hospital-based controls recruited during 1996-1997. Four subgroups of cases were studied: (i) all CRCs; (ii) a molecular CRC subgroup (n = 117, cases with molecular tumor analyses); (iii) within the molecular subgroup those tumors with K-ras mutations in codon 12 (CRC K12); (iv) within the molecular subgroup those tumors with K-ras mutations in codon 13 (CRC K13). The C609T NQO1 genotype was found to be twice as prevalent in all CRC patients (6.8%) compared with controls (3%) and six times more common in the subset CRC K12 (20%). Multivariant analyses in the overall population of 247 cases and 296 controls showed a significant age and gender adjusted risk for CRC associated with the C609T NQO1 genotype (OR 2.9, 95% CI 1.19-6.97; P = 0.01) or with any variant genotype (the low activity allele frequency, i.e. heterozygotes plus homozygotes) (OR 1.41, 95% CI 1.02-1.92; P = 0.03). Within cases of the molecular subgroup (n = 117) the C609T NQO1 genotype was associated with the presence of K-ras codon 12 mutation (OR 6.5 95%, CI 1.39-34.9; P = 0.003). Logistic regression showed an age and gender adjusted risk for K-ras codon 12 mutant CRC associated with the C609T NQO1 genotype (OR 10.5, 95% CI 2.99-36.7; P: = 0.0002) or with any variant NQO1 genotype (OR 2.23, 95% CI 1.23-4.00; P = 0.007) compared with the control group. Genetically determined variations in NQO1 may modify the risk for CRC and these risks may be greatest for tumors containing K-ras codon 12 mutations. CRC with K-ras codon 12 mutations may represent a distinct and etiologically more homogeneous subtype of the disease, which may be associated with toxicants that are metabolized via a NQO1-dependent pathway.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0143-3334
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
21
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1813-9
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11023538-Age Factors,
pubmed-meshheading:11023538-Aged,
pubmed-meshheading:11023538-Case-Control Studies,
pubmed-meshheading:11023538-Colorectal Neoplasms,
pubmed-meshheading:11023538-Female,
pubmed-meshheading:11023538-Genes, ras,
pubmed-meshheading:11023538-Genetic Predisposition to Disease,
pubmed-meshheading:11023538-Genotype,
pubmed-meshheading:11023538-Humans,
pubmed-meshheading:11023538-Male,
pubmed-meshheading:11023538-Middle Aged,
pubmed-meshheading:11023538-Multivariate Analysis,
pubmed-meshheading:11023538-Mutation,
pubmed-meshheading:11023538-NAD(P)H Dehydrogenase (Quinone),
pubmed-meshheading:11023538-Neoplasm Staging,
pubmed-meshheading:11023538-Polymorphism, Genetic,
pubmed-meshheading:11023538-Risk Factors,
pubmed-meshheading:11023538-Sex Factors,
pubmed-meshheading:11023538-Smoking,
pubmed-meshheading:11023538-Socioeconomic Factors
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| pubmed:year |
2000
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| pubmed:articleTitle |
NAD(P)H:quinone oxidoreductase-dependent risk for colorectal cancer and its association with the presence of K-ras mutations in tumors.
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| pubmed:affiliation |
Department of Surgery, Hospital Clinic, Department of Pharmacology, School of Medicine, Casanova 143, E-08036, Barcelona, Spain. alafuente@med.ub.es
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|