Document Detail


Occupational trichloroethylene exposure and renal carcinoma risk: evidence of genetic susceptibility by reductive metabolism gene variants.
MedLine Citation:
PMID:  20663906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >or=1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.
Authors:
Lee E Moore; Paolo Boffetta; Sara Karami; Paul Brennan; Patricia S Stewart; Rayjean Hung; David Zaridze; Vsevolod Matveev; Vladimir Janout; Helena Kollarova; Vladimir Bencko; Marie Navratilova; Neonila Szeszenia-Dabrowska; Dana Mates; Jan Gromiec; Ivana Holcatova; Maria Merino; Stephen Chanock; Wong-Ho Chow; Nathaniel Rothman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2010-07-27
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-11-10     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6527-36     Citation Subset:  IM    
Copyright Information:
(c)2010 AACR.
Affiliation:
Division of Cancer Epidemiology and Genetics, NIH, National Cancer Institute, NIH, Bethesda, Maryland 20852, USA. moorele@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Carbon-Sulfur Lyases / genetics,  metabolism
Case-Control Studies
Cocarcinogenesis*
Female
Genetic Predisposition to Disease
Glutathione Transferase / genetics,  metabolism
Humans
Kidney Neoplasms / chemically induced*,  enzymology,  genetics*
Male
Occupational Exposure / adverse effects*
Polymorphism, Single Nucleotide
Trichloroethylene / poisoning*
Grant Support
ID/Acronym/Agency:
Z99 CA999999/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
79-01-6/Trichloroethylene; EC 2.5.1.-/glutathione S-transferase T1; EC 2.5.1.18/Glutathione Transferase; EC 4.4.-/Carbon-Sulfur Lyases; EC 4.4.1.6/S-alkylcysteine lyase
Comments/Corrections

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