This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lan, Q. Articles by Rothman, N. Search for Related Content PubMed PubMed Citation Articles by Lan, Q. Articles by Rothman, N.

Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene

¹ Division of Cancer Epidemiology and Genetics and ² Center for Cancer Research, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ³ School of Public Health, University of California, Berkeley, California; ⁴ Chinese Center for Disease Control and Prevention, Beijing, China; ⁵ School of Public Health, University of North Carolina, Chapel Hill, North Carolina; and ⁶ New York Blood Center, Clinical Services, White Plains, New York

Requests for reprints: Qing Lan, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, MSC 7240, 6120 Executive Boulevard, EPS 8109, Bethesda, MD 20892-7240. Phone: 301-435-4706; Fax: 301-402-1819; E-mail: qingl{at}mail.nih.gov.

Benzene is a recognized hematotoxin and leukemogen but its mechanism of action and the role of genetic susceptibility are still unclear. Cytokines, chemokines, and cellular adhesion molecules are soluble proteins that play an important regulatory role in hematopoiesis. We therefore hypothesized that variation in these genes could influence benzene-induced hematotoxicity. We analyzed common, well-studied single-nucleotide polymorphisms (SNPs) in 20 candidate genes drawn from these pathways in a study of 250 workers exposed to benzene and 140 unexposed controls in China. After accounting for multiple comparisons, SNPs in five genes were associated with a statistically significant decrease in total WBC counts among exposed workers [IL-1A (–889C>T), IL-4 (–1098T>G), IL-10 (–819T>C), IL-12A (8685G>A), and VCAM1 (–1591T>C)], and one SNP [CSF3 (Ex4–165C>T)] was associated with an increase in WBC counts. The adhesion molecule VCAM1 variant was particularly noteworthy as it was associated with a decrease in B cells, natural killer cells, CD4⁺ T cells, and monocytes. Further, VCAM1 (–1591T>C) and CSF3 (Ex4–165C>T) were associated, respectively, with decreased (P = 0.041) and increased (P = 0.076) CFU-GEMM progenitor cell colony formation in 29 benzene-exposed workers. This is the first report to provide evidence that SNPs in genes that regulate hematopoiesis influence benzene-induced hematotoxicity.

This article has been cited by other articles:

				Q. Lan, L. Zhang, M. Shen, W. J. Jo, R. Vermeulen, G. Li, C. Vulpe, S. Lim, X. Ren, S. M. Rappaport, et al. Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity Carcinogenesis, January 1, 2009; 30(1): 50 - 58. [Abstract] [Full Text] [PDF]

				J-Q. He, K. Shumansky, J. E. Connett, N. R. Anthonisen, P. D. Pare, and A. J. Sandford Association of genetic variations in the CSF2 and CSF3 genes with lung function in smoking-induced COPD Eur. Respir. J., July 1, 2008; 32(1): 25 - 34. [Abstract] [Full Text] [PDF]

				P. Vineis and F. Perera Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 547 - 567. [Abstract] [Full Text] [PDF]

				N. S. Young and D. W. Kaufman The epidemiology of acquired aplastic anemia Haematologica, April 1, 2008; 93(4): 489 - 492. [Full Text] [PDF]

				P A Schulte The contributions of genetics and genomics to occupational safety and health Occup. Environ. Med., November 1, 2007; 64(11): 717 - 718. [Full Text] [PDF]

				P. Vineis and F. Perera Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1954 - 1965. [Abstract] [Full Text] [PDF]