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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1996-9-30
pubmed:abstractText
Foreign compound-metabolizing enzymes may modify the risk of chemically induced cancer. We wanted to examine enzymes with putative relevance in urinary bladder cancer using molecular genetic analyses of heritably polymorphic enzymes. Arylamine N-acetyltransferase (NAT2); glutathione S-transferases (GSTs) M1 and T1; microsomal epoxide hydrolase; and cytochrome P-450 enzymes (CYP) 1A1, 2C19, 2D6, and 2E1 were analyzed in 374 cases and in 373 controls in a hospital-based case-control study in Berlin. Slow acetylation was a significant risk factor in heavy smokers [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.0-7.4], with the greatest risk noted for the allele NAT2*5B. GSTM1 deficiency was a risk factor independent of smoking and occupation (OR, 1.6; CI, 1.2-2.2). GSTT1 was associated with cancer risk in the nonsmoker subgroup (OR, 2.6; CI, 1.1-6.0). The two amino acid polymorphisms that are known in microsomal epoxide hydrolase were not associated with bladder cancer risk. CYP2D6 activity was rejected as a risk factor by phenotyping and by detailed molecular genetic analyses. CYP2C19 may have a role in bladder cancer risk, but polymorphisms in CYP1A1 and 2E1 had no statistically significant impact. Deficiencies in both NAT2 and GSTM1 failed to show significant synergistic or antagonistic interactions. In conclusion, molecular genetic analysis of a large sample specified the increased bladder cancer risk of those who are deficient in NAT2 and GSTM1; the other traits proved to be of minor impact.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3915-25
pubmed:dateRevised
2010-9-8
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk.
pubmed:affiliation
Institut für Klinische Pharmakologie, Universitätklinikum Charite, Humboldt-Universität, zu Berlin, Germany.
pubmed:publicationType
Journal Article