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Titolo:
Risk assessment: the importance of genetic polymorphisms in man
Autore:
Knudsen, LE; Loft, SH; Autrup, H;
Indirizzi:
Univ Copenhagen, Inst Publ Hlth, Dept Environm & Occupat Med, DK-2200 Copenhagen N, Denmark Univ Copenhagen Copenhagen Denmark N Med, DK-2200 Copenhagen N, Denmark Aarhus Univ, Inst Environm Med, DK-8000 Aarhus, Denmark Aarhus Univ Aarhus Denmark DK-8000 Environm Med, DK-8000 Aarhus, Denmark
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 482, anno: 2001,
pagine: 83 - 88
SICI:
1386-1964(20011001)482:1-2<83:RATIOG>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
PREDICT HUMAN CANCER; S-TRANSFERASE M1; CHROMOSOMAL-ABERRATIONS; AIR-POLLUTION; ADDUCT LEVELS; DNA-REPAIR; EXPOSURE; LYMPHOCYTES; BIOMARKERS; SUSCEPTIBILITY;
Keywords:
glutathion-S-transferase M1 (GSTM1); N-acetyltransferase 2 (NAT2); genetic polymorphism; environmental toxicants; chromosomal aberrations;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: Knudsen, LE Univ Copenhagen, Inst Publ Hlth, Dept Environm & Occupat Med, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark Univ Copenhagen Blegdamsvej 3 Copenhagen Denmark N N, Denmark
Citazione:
L.E. Knudsen et al., "Risk assessment: the importance of genetic polymorphisms in man", MUT RES-F M, 482(1-2), 2001, pp. 83-88

Abstract

Many genetic polymorphisms in metabolism enzymes are important for the risk of cancer as shown in a large number of case-control studies. The relative risk estimates have shown large variations between such population studies. However, in most studies the relative risk estimates are in the range of2. Some polymorphisms are effect modifiers, i.e. without exposure they have no consequence and the effect of exposure can appear independent of the genotype. Genetic polymorphisms in metabolism of environmental toxicants plays a significant role in exposures to traffic generated air pollution in Copenhagen, revealing statistically significant higher levels of chromosomal aberrations in non-smoking bus drivers with glutathion-S-transferase M1, GSTM1 null and N-acetyltransferase 2, NAT2 slow genotypes. Combined with cohort studies showing positive associations between high chromosomal levels and increased cancer risk, such results indicate effect modification regarding cancer risk. In risk assessment the safety 'factor' of 10 is generally accepted to allow for variation in individual susceptibility. Reviewing the literature justifies the factor of 10 when considering single polymorphisms. However in anindividual with several susceptible metabolism genotypes as well as other determinants of susceptibility, e.g. defective DNA repair, poor-nutritionalstate, etc. the risk may increase far above a safety of 10. Historically, genetic polymorphisms have been taken into consideration in employment and currently the application in insurance situations is criticised. (C) 2001 Elsevier Science B.V. All rights reserved.

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Documento generato il 02/04/20 alle ore 18:22:07