Source:http://linkedlifedata.com/resource/pubmed/id/11597790
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2001-10-12
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| pubmed:abstractText |
Human microsomal epoxide hydrolase (mEH) catalyzes a key step in the biotransformation of benzo[a]pyrene that yields the highly mutagenic (+)-anti-7,8-diol-9,10 epoxide (BPDE). Two polymorphisms have been described in the coding region of the mEH gene (EPHX1) that produce two protein variants: 113Tyr-->113His (exon 3) and 139His-->139Arg (exon 4). We performed a case-control study among Northwestern Mediterranean Caucasians to investigate a possible association between these EPHX1 variants and lung cancer risk. Both EPHX1 polymorphisms were analyzed in a group of lung cancer patients (n=176) and in a control group of healthy smokers (n=187). The results showed a significantly decreased risk for the rare homozygous 113His/113His (adjusted odds ratio (OR): 0.44, 95% confidence interval (CI): 0.27-0.71) and 139Arg/139Arg (adjusted OR: 0.55, 95% CI: 0.33-0.91) compared with the major wild-types 113Tyr/113Tyr and 139His/139His, respectively, as the references. Thereafter, we analyzed the EPHX1 variants in combination with three glutathione S-transferase polymorphic genes (GSTM1, GSTT1, and GSTP1) and we found a significant overepresentation of cancer patients with a combination of exon 3 113Tyr/113Tyr EPHX1 and exon 5 105Ile/105Ile GSTP1 (adjusted OR: 2.34, 95% CI: 1.21-4.52). The polymorphic site within the exon 5 of GSTP1 results in a Ile-->Val substitution, and the isoleucine GSTpi isoform has been found in vitro to be less active than the valine isoform towards the conjugation of BPDE. The 113 Tyr/Tyr EPHX1 encodes for a high-activity mEH. Our results agree with these observations in vitro and suggest that a genetically determined combination of a high-activity mEH and a low-activity GSTpi may increase lung cancer risk among smokers.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epoxide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0304-3835
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
28
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| pubmed:volume |
173
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
155-62
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11597790-Adult,
pubmed-meshheading:11597790-Aged,
pubmed-meshheading:11597790-Aged, 80 and over,
pubmed-meshheading:11597790-Epoxide Hydrolases,
pubmed-meshheading:11597790-Exons,
pubmed-meshheading:11597790-Female,
pubmed-meshheading:11597790-Genetic Predisposition to Disease,
pubmed-meshheading:11597790-Genotype,
pubmed-meshheading:11597790-Glutathione Transferase,
pubmed-meshheading:11597790-Histidine,
pubmed-meshheading:11597790-Homozygote,
pubmed-meshheading:11597790-Humans,
pubmed-meshheading:11597790-Lung Neoplasms,
pubmed-meshheading:11597790-Male,
pubmed-meshheading:11597790-Microsomes,
pubmed-meshheading:11597790-Middle Aged,
pubmed-meshheading:11597790-Odds Ratio,
pubmed-meshheading:11597790-Phenotype,
pubmed-meshheading:11597790-Polymorphism, Genetic,
pubmed-meshheading:11597790-Protein Isoforms,
pubmed-meshheading:11597790-Smoking,
pubmed-meshheading:11597790-Tyrosine
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| pubmed:year |
2001
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| pubmed:articleTitle |
Lung cancer susceptibility in relation to combined polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase P1.
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| pubmed:affiliation |
Toxicology Unit, Hospital Clínic, IDIBAPS, Departament de Salut Pública, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain. jtofigue@medicina.ub.es
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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