Occupational trichloroethylene exposure and renal carcinoma risk: Evidence of genetic susceptibility by reductive metabolism gene variants

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

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine β-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; Ptrend = 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; Pinteraction = 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; Ptrend = 1.00; P interaction = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with ≥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.

Original languageEnglish (US)
Pages (from-to)6527-6536
Number of pages10
JournalCancer Research
Issue number16
StatePublished - Aug 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Occupational trichloroethylene exposure and renal carcinoma risk: Evidence of genetic susceptibility by reductive metabolism gene variants'. Together they form a unique fingerprint.

Cite this