TY - JOUR
T1 - Polymorphisms in cytokine and cellular adhesion molecule gene and susceptibility to hematotoxicity among workers exposed to benzene
AU - Lan, Qing
AU - Zhang, Luoping
AU - Shen, Min
AU - Smith, Martyn T.
AU - Li, Guilan
AU - Vermeulen, Roel
AU - Rappaport, Stephen M.
AU - Forrest, Matthew S.
AU - Hayes, Richard B.
AU - Linet, Martha
AU - Dosemeci, Mustafa
AU - Alter, Blanche P.
AU - Weinberg, Rona S.
AU - Yin, Songnian
AU - Yeager, Meredith
AU - Welch, Robert
AU - Waidyanatha, Suramya
AU - Kim, Sungkyoon
AU - Chanock, Stephen
AU - Rothman, Nathaniel
PY - 2005/10/15
Y1 - 2005/10/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-05-1419
DO - 10.1158/0008-5472.CAN-05-1419
M3 - Article
C2 - 16230423
AN - SCOPUS:27144553722
VL - 65
SP - 9574
EP - 9581
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 20
ER -