Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity

Howard D. Hosgood, L. Zhang, M. Shen, S. I. Berndt, R. Vermeulen, G. Li, S. Yin, M. Yeager, J. Yuenger, N. Rothman, S. Chanock, M. Smith, Q. Lan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: Benzene is an established human haematotoxin, with substantial interindividual variation in benzene-induced toxicity. Methods: To further examine if genetic variation contributes to benzene haematotoxicity, we analysed 1023 tagSNPs in 121 gene regions important for benzene metabolism, haematopoiesis, leukaemia and lymphoma among 250 workers exposed to benzene and 140 unexposed controls in a cross-sectional study carried out in China. Linear regression was used to analyse the relationship between genetic polymorphisms and total white blood cell (WBC) count and its subtypes, adjusting for potential confounders and occupational exposure to benzene and toluene among exposed workers. The minp test assessed the association on the gene region level. The false discovery rate method was used to control for multiple comparisons. Results: VEGF (minp=0.0030) and ERCC3 (minp=0.0042) were the most significantly associated gene regions with altered WBC counts among benzeneexposed workers, after accounting for multiple comparisons. Highly significant changes were also found for WBC subtype counts, including granulocytes, CD4+ T cells and lymphocytes for VEGF and granulocytes and NK cells for ERCC3. Further, in workers exposed to <1 ppm, a SNP in VEGF was associated with changes in WBC and granulocyte counts, and SNPs in ERCC3 were associated with changes in WBC, NK cell and granulocyte counts. Discussion: Our findings suggest that genetic variation in VEGF, which plays an important role in blood vessel growth, and ERCC3, which is a member of the DNA repair pathway and is responsible for repairing bulky DNA adducts formed by chemicals, may contribute to individual susceptibility to benzene-induced haematotoxicity at relatively low levels of benzene exposure.

Original languageEnglish (US)
Pages (from-to)848-853
Number of pages6
JournalOccupational and Environmental Medicine
Volume66
Issue number12
DOIs
StatePublished - Dec 2009
Externally publishedYes

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Benzene
Vascular Endothelial Growth Factor A
Leukocyte Count
Granulocytes
Natural Killer Cells
Single Nucleotide Polymorphism
Genes
T-Lymphocytes
DNA Adducts
Hematopoiesis
Toluene
Genetic Polymorphisms
Occupational Exposure
DNA Repair
Blood Vessels
Linear Models
Lymphoma
China
Leukemia
Leukocytes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity. / Hosgood, Howard D.; Zhang, L.; Shen, M.; Berndt, S. I.; Vermeulen, R.; Li, G.; Yin, S.; Yeager, M.; Yuenger, J.; Rothman, N.; Chanock, S.; Smith, M.; Lan, Q.

In: Occupational and Environmental Medicine, Vol. 66, No. 12, 12.2009, p. 848-853.

Research output: Contribution to journalArticle

Hosgood, HD, Zhang, L, Shen, M, Berndt, SI, Vermeulen, R, Li, G, Yin, S, Yeager, M, Yuenger, J, Rothman, N, Chanock, S, Smith, M & Lan, Q 2009, 'Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity', Occupational and Environmental Medicine, vol. 66, no. 12, pp. 848-853. https://doi.org/10.1136/oem.2008.044024
Hosgood, Howard D. ; Zhang, L. ; Shen, M. ; Berndt, S. I. ; Vermeulen, R. ; Li, G. ; Yin, S. ; Yeager, M. ; Yuenger, J. ; Rothman, N. ; Chanock, S. ; Smith, M. ; Lan, Q. / Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity. In: Occupational and Environmental Medicine. 2009 ; Vol. 66, No. 12. pp. 848-853.
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AU - Hosgood, Howard D.

AU - Zhang, L.

AU - Shen, M.

AU - Berndt, S. I.

AU - Vermeulen, R.

AU - Li, G.

AU - Yin, S.

AU - Yeager, M.

AU - Yuenger, J.

AU - Rothman, N.

AU - Chanock, S.

AU - Smith, M.

AU - Lan, Q.

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N2 - Introduction: Benzene is an established human haematotoxin, with substantial interindividual variation in benzene-induced toxicity. Methods: To further examine if genetic variation contributes to benzene haematotoxicity, we analysed 1023 tagSNPs in 121 gene regions important for benzene metabolism, haematopoiesis, leukaemia and lymphoma among 250 workers exposed to benzene and 140 unexposed controls in a cross-sectional study carried out in China. Linear regression was used to analyse the relationship between genetic polymorphisms and total white blood cell (WBC) count and its subtypes, adjusting for potential confounders and occupational exposure to benzene and toluene among exposed workers. The minp test assessed the association on the gene region level. The false discovery rate method was used to control for multiple comparisons. Results: VEGF (minp=0.0030) and ERCC3 (minp=0.0042) were the most significantly associated gene regions with altered WBC counts among benzeneexposed workers, after accounting for multiple comparisons. Highly significant changes were also found for WBC subtype counts, including granulocytes, CD4+ T cells and lymphocytes for VEGF and granulocytes and NK cells for ERCC3. Further, in workers exposed to <1 ppm, a SNP in VEGF was associated with changes in WBC and granulocyte counts, and SNPs in ERCC3 were associated with changes in WBC, NK cell and granulocyte counts. Discussion: Our findings suggest that genetic variation in VEGF, which plays an important role in blood vessel growth, and ERCC3, which is a member of the DNA repair pathway and is responsible for repairing bulky DNA adducts formed by chemicals, may contribute to individual susceptibility to benzene-induced haematotoxicity at relatively low levels of benzene exposure.

AB - Introduction: Benzene is an established human haematotoxin, with substantial interindividual variation in benzene-induced toxicity. Methods: To further examine if genetic variation contributes to benzene haematotoxicity, we analysed 1023 tagSNPs in 121 gene regions important for benzene metabolism, haematopoiesis, leukaemia and lymphoma among 250 workers exposed to benzene and 140 unexposed controls in a cross-sectional study carried out in China. Linear regression was used to analyse the relationship between genetic polymorphisms and total white blood cell (WBC) count and its subtypes, adjusting for potential confounders and occupational exposure to benzene and toluene among exposed workers. The minp test assessed the association on the gene region level. The false discovery rate method was used to control for multiple comparisons. Results: VEGF (minp=0.0030) and ERCC3 (minp=0.0042) were the most significantly associated gene regions with altered WBC counts among benzeneexposed workers, after accounting for multiple comparisons. Highly significant changes were also found for WBC subtype counts, including granulocytes, CD4+ T cells and lymphocytes for VEGF and granulocytes and NK cells for ERCC3. Further, in workers exposed to <1 ppm, a SNP in VEGF was associated with changes in WBC and granulocyte counts, and SNPs in ERCC3 were associated with changes in WBC, NK cell and granulocyte counts. Discussion: Our findings suggest that genetic variation in VEGF, which plays an important role in blood vessel growth, and ERCC3, which is a member of the DNA repair pathway and is responsible for repairing bulky DNA adducts formed by chemicals, may contribute to individual susceptibility to benzene-induced haematotoxicity at relatively low levels of benzene exposure.

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