title: Polymorphisms in genes involved in innate immunity and susceptibility to benzene-induced hematotoxicity.
abstract: Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P<0.05) and SNP analyses (FDR<0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.
authors.affiliation: Division of Cancer Epidemiology and Genetics NCI, NIH, DHHS, Bethesda MD 20892, U.S.A.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Kyoung Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.forename: Songnian
authors.initials: S
authors.lastname: Yin
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001554:Benzene / Q000633:toxicity; D002452:Cell Count; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006402:Hematologic Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D009195:Peroxidase; D001094:Arachidonate 5-Lipoxygenase; D001554:Benzene