Polymorphisms in cytokine and cellular adhesion molecule gene and susceptibility to hematotoxicity among workers exposed to benzene

Qing Lan, Luoping Zhang, Min Shen, Martyn T. Smith, Guilan Li, Roel Vermeulen, Stephen M. Rappaport, Matthew S. Forrest, Richard B. Hayes, Martha Linet, Mustafa Dosemeci, Blanche P. Alter, Rona S. Weinberg, Songnian Yin, Meredith Yeager, Robert Welch, Suramya Waidyanatha, Sungkyoon Kim, Stephen Chanock, Nathaniel Rothman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9574-9581
Number of pages8
JournalCancer Research
Volume65
Issue number20
DOIs
StatePublished - Oct 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Polymorphisms in cytokine and cellular adhesion molecule gene and susceptibility to hematotoxicity among workers exposed to benzene'. Together they form a unique fingerprint.

Cite this