Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity

Biomarker: single nucleotide polymorphisms (SNPs) in each of seven genes (WRN, TP53, NBS1, BRCA1, BRCA2, XRCC3 and XRCC4); alleles studied: WRN (Ex4 -16 G > A, Ex6 +9 C > T, Ex20 -88 G > T and Ex26 -12 T > G); TP53 (Ex4 +119 C > G); BRCA2 (Ex11 +1487 A > G)Effect studied: DNA damage. Tissue/biological material/sample size: blood. Method of analysis: TaqMan-based real-time PCR. Study design: case-control studyStudy size: 250 workers exposed to benzene and 140 unexposed controlsImpact on outcome (including dose-response): Four SNPs in WRN (Ex4 -16 G > A, Ex6 +9 C > T, Ex20 -88 G > T and Ex26 -12 T > G), one SNP in TP53 (Ex4 +119 C > G) and one SNP in BRCA2 (Ex11 +1487 A > G) were associated with a statistically significant decrease in total white blood cell (WBC) counts among exposed workers. The SNPs in WRN and TP53 remained significant after accounting for multiple comparisons. One or more SNPs in WRN had broad effects on WBC subtypes, with significantly decreased granulocyte, total lymphocyte, CD4(+)-T cell, CD8(+)-T cell and monocyte counts. Haplotypes of WRN were associated with decreased WBC counts among benzene-exposed subjects. Likewise, subjects with TP53 Ex4 +119 C > G variant had reduced granulocyte, CD4(+)-T cell and B cell counts. The effect of BRCA2 Ex11 +1487 A > G polymorphism was limited to granulocytes. keywords - classification: Adult;Alleles;analysis;Benzene;biomarkers of individual susceptibility: field studies;blood;Blood Cells;China;Cross-Sectional Studies;DNA Helicases;DNA Repair;drug effects;Epidemiology;Female;field studies;Genes,Brca2;Genes,p53;genetic;Genetic Predisposition to Disease;genetics;Haplotypes;history;Humans;Male;Polymorphism,Single Nucleotide;RecQ Helicases;Research;toxicity;