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

doi:10.1158/0008-5472.CAN-09-4167

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

National Institutes of Health
International Agency for Research on Cancer
Stewart Exposure Assessments, LLC
University of Toronto
Blokhin Cancer Research Center
Palacký University Olomouc
Charles University
Masaryk Memorial Cancer Institute
Nofer Institute of Occupational Medicine
National Institute of Public Health

Research output: Contribution to journal › Article › peer-review

101 Scopus citations

Abstract

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; 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 ≥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 language	English
Pages (from-to)	6527-6536
Number of pages	10
Journal	Cancer Research
Volume	70
Issue number	16
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-4167
State	Published - Aug 15 2010

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Moore, L. E., Boffetta, P., Karami, S., Brennan, P., Stewart, P. S., Hung, R., Zaridze, D., Matveev, V., Janout, V., Kollarova, H., Bencko, V., Navratilova, M., Szeszenia-Dabrowska, N., Mates, D., Gromiec, J., Holcatova, I., Merino, M., Chanock, S., Chow, W. H., & Rothman, N. (2010). Occupational trichloroethylene exposure and renal carcinoma risk: Evidence of genetic susceptibility by reductive metabolism gene variants. Cancer Research, 70(16), 6527-6536. https://doi.org/10.1158/0008-5472.CAN-09-4167

@article{e7195f9f635349ae8351ce576e287177,

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

abstract = "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.",

author = "Moore, \{Lee E.\} and Paolo Boffetta and Sara Karami and Paul Brennan and Stewart, \{Patricia S.\} and Rayjean Hung and David Zaridze and Vsevolod Matveev and Vladimir Janout and Helena Kollarova and Vladimir Bencko and Marie Navratilova and Neonila Szeszenia-Dabrowska and Dana Mates and Jan Gromiec and Ivana Holcatova and Maria Merino and Stephen Chanock and Chow, \{Wong Ho\} and Nathaniel Rothman",

year = "2010",

month = aug,

day = "15",

doi = "10.1158/0008-5472.CAN-09-4167",

language = "English",

volume = "70",

pages = "6527--6536",

journal = "Cancer Research",

issn = "0008-5472",

number = "16",

}

Moore, LE, Boffetta, P, Karami, S, Brennan, P, Stewart, PS, Hung, R, Zaridze, D, Matveev, V, Janout, V, Kollarova, H, Bencko, V, Navratilova, M, Szeszenia-Dabrowska, N, Mates, D, Gromiec, J, Holcatova, I, Merino, M, Chanock, S, Chow, WH & Rothman, N 2010, 'Occupational trichloroethylene exposure and renal carcinoma risk: Evidence of genetic susceptibility by reductive metabolism gene variants', Cancer Research, vol. 70, no. 16, pp. 6527-6536. https://doi.org/10.1158/0008-5472.CAN-09-4167

TY - JOUR

T1 - Occupational trichloroethylene exposure and renal carcinoma risk

T2 - Evidence of genetic susceptibility by reductive metabolism gene variants

AU - Moore, Lee E.

AU - Boffetta, Paolo

AU - Karami, Sara

AU - Brennan, Paul

AU - Stewart, Patricia S.

AU - Hung, Rayjean

AU - Zaridze, David

AU - Matveev, Vsevolod

AU - Janout, Vladimir

AU - Kollarova, Helena

AU - Bencko, Vladimir

AU - Navratilova, Marie

AU - Szeszenia-Dabrowska, Neonila

AU - Mates, Dana

AU - Gromiec, Jan

AU - Holcatova, Ivana

AU - Merino, Maria

AU - Chanock, Stephen

AU - Chow, Wong Ho

AU - Rothman, Nathaniel

PY - 2010/8/15

Y1 - 2010/8/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/77955732577

U2 - 10.1158/0008-5472.CAN-09-4167

DO - 10.1158/0008-5472.CAN-09-4167

M3 - Article

C2 - 20663906

AN - SCOPUS:77955732577

SN - 0008-5472

VL - 70

SP - 6527

EP - 6536

JO - Cancer Research

JF - Cancer Research

IS - 16

ER -

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

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