The impact of saturable metabolism on exposure-response relations in 2 studies of benzene-induced leukemia.

2.50
Hdl Handle:
http://hdl.handle.net/10146/197609
Title:
The impact of saturable metabolism on exposure-response relations in 2 studies of benzene-induced leukemia.
Authors:
Vlaanderen, Jelle; Portengen, Lutzen; Rappaport, Stephen M.; Glass, Deborah C.; Kromhout, Hans; Vermeulen, Roel
Abstract:
Enzymatic saturation of metabolic pathways is one factor that potentially contributes to the nonlinear exposure-response relations that are frequently reported in occupational epidemiologic studies. The authors propose an approach to explore the contribution of saturable metabolism to previously reported exposure-response relations by integrating predictive models of relevant biomarkers of exposure into the epidemiologic analysis. The approach is demonstrated with 2 studies of leukemia in benzene-exposed workers, one conducted in the Australian petroleum industry (1981-1999) and one conducted in a US rubber hydrochloride production factory in Ohio (1940-1996). The studies differed greatly in their magnitudes and durations of exposure. Substitution of biomarker levels for external estimates of benzene exposure reduced the fold difference of the log relative risk of leukemia per unit of cumulative exposure between the 2 studies by 11%-44%. Nevertheless, a considerable difference in the log relative risk per unit of cumulative exposure remained between the 2 studies, suggesting that exposure misclassification, differences in study design, and potential confounding factors also contributed to the heterogeneity in risk estimates.
Citation:
Am. J. Epidemiol. 2011, 174 (5):621-629
Journal:
American Journal of Epidemiology
Issue Date:
1-Sep-2011
URI:
http://hdl.handle.net/10146/197609
DOI:
10.1093/aje/kwr118
PubMed ID:
21745798
Additional Links:
http://aje.oxfordjournals.org/content/174/5/621.long
Type:
Article
Language:
en
ISSN:
1476-6256
Sponsors:
This work was performed as part of the work package ‘‘integrated risk assessment’’ of the ECNIS Network of Excellence (Environmental Cancer Risk, Nutrition, and Individual Susceptibility), operating within the European Union’s 6th Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (FOOD-CT-2005-513943).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorVlaanderen, Jelleen
dc.contributor.authorPortengen, Lutzenen
dc.contributor.authorRappaport, Stephen M.en
dc.contributor.authorGlass, Deborah C.en
dc.contributor.authorKromhout, Hansen
dc.contributor.authorVermeulen, Roelen
dc.date.accessioned2011-12-16T11:00:10Z-
dc.date.available2011-12-16T11:00:10Z-
dc.date.issued2011-09-01-
dc.identifier.citationAm. J. Epidemiol. 2011, 174 (5):621-629en
dc.identifier.issn1476-6256-
dc.identifier.pmid21745798-
dc.identifier.doi10.1093/aje/kwr118-
dc.identifier.urihttp://hdl.handle.net/10146/197609-
dc.description.abstractEnzymatic saturation of metabolic pathways is one factor that potentially contributes to the nonlinear exposure-response relations that are frequently reported in occupational epidemiologic studies. The authors propose an approach to explore the contribution of saturable metabolism to previously reported exposure-response relations by integrating predictive models of relevant biomarkers of exposure into the epidemiologic analysis. The approach is demonstrated with 2 studies of leukemia in benzene-exposed workers, one conducted in the Australian petroleum industry (1981-1999) and one conducted in a US rubber hydrochloride production factory in Ohio (1940-1996). The studies differed greatly in their magnitudes and durations of exposure. Substitution of biomarker levels for external estimates of benzene exposure reduced the fold difference of the log relative risk of leukemia per unit of cumulative exposure between the 2 studies by 11%-44%. Nevertheless, a considerable difference in the log relative risk per unit of cumulative exposure remained between the 2 studies, suggesting that exposure misclassification, differences in study design, and potential confounding factors also contributed to the heterogeneity in risk estimates.en
dc.description.sponsorshipThis work was performed as part of the work package ‘‘integrated risk assessment’’ of the ECNIS Network of Excellence (Environmental Cancer Risk, Nutrition, and Individual Susceptibility), operating within the European Union’s 6th Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (FOOD-CT-2005-513943).en
dc.language.isoenen
dc.relation.urlhttp://aje.oxfordjournals.org/content/174/5/621.longen
dc.subjectBenzeneen
dc.subjectOccupational exposureen
dc.subjectPetroleum industryen
dc.subjectLeukemiaen
dc.subjectMetabolismen
dc.subjectPharmacokineticsen
dc.subjectCase-Control Studiesen
dc.subjectCohort Studiesen
dc.subject.meshBenzene-
dc.subject.meshBiological Markers-
dc.subject.meshHumans-
dc.subject.meshLeukemia-
dc.subject.meshOccupational Diseases-
dc.subject.meshOccupational Exposure-
dc.subject.meshRisk Assessment-
dc.subject.meshUrinalysis-
dc.titleThe impact of saturable metabolism on exposure-response relations in 2 studies of benzene-induced leukemia.en
dc.typeArticleen
dc.identifier.journalAmerican Journal of Epidemiologyen
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