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Shen, Min,Zhang, Luoping,Lee, Kyoung-Mu,Vermeulen, Roel,Hosgood, H. Dean,Li, Guilan,Yin, Songnian,Rothman, Nathaniel,Chanock, Stephen,Smith, Martyn T.,Lan, Qing Korean Society for Biochemistry and Molecular Bion 2011 Experimental and molecular medicine Vol.43 No.6
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.
Min Shen,H. Dean Hosgood,Luoping Zhang,이경무,Roel Vermeulen,Guilan Li,Songnian Yin,Nathaniel Rothman,Stephen Chanock,Martyn T. Smith,Qing Lan 생화학분자생물학회 2011 Experimental and molecular medicine Vol.43 No.6
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 149gene 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.
Liao, Linda M,Friesen, Melissa C,Xiang, Yong-Bing,Cai, Hui,Koh, Dong-Hee,Ji, Bu-Tian,Yang, Gong,Li, Hong-Lan,Locke, Sarah J,Rothman, Nathaniel,Zheng, Wei,Gao, Yu-Tang,Shu, Xiao-Ou,Purdue, Mark P BMJ Publishing Group Ltd 2014 Occupational and environmental medicine Vol.71 No.suppl1
<P><B>Objectives</B></P><P>Epidemiologic studies of occupational lead exposure have suggested increased risks of cancers of the brain, kidney, lung, meninges, and stomach; however, the totality of the evidence is inconsistent. To clarify whether lead is a carcinogen, we investigated the relationship between occupational lead exposure and risks of these five cancer sites in two prospective cohort studies in Shanghai, China.</P><P><B>Method</B></P><P>Annual job/industry-specific estimates of lead fume and lead dust exposure were derived from a statistical model that combined expert ratings of lead intensity with inspection measurements collected by the Shanghai Centre for Disease Control and Prevention. The job/industry estimates were applied to the lifetime work histories of subjects from the Shanghai Women’s Health Study (73 363 participants) and the Shanghai Men’s Health Study (61 379 participants) to estimate cumulative exposure to lead dust and lead fume. Cohort-specific relative hazard rate ratios (RRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models and then pooled using a random effects meta-analysis model.</P><P><B>Results</B></P><P>We observed a statistically significant increased risk of meningioma among individuals with estimated occupational exposure to lead dust or fumes (RR=2.4, 95% CI:1.1–5.0), and in particular among those with an above-median cumulative exposure to dust or fumes (RR=3.1, 95% CI:1.3–7.4). We observed suggestive associations with lead exposure for cancers of the kidney (RR=1.4, 95% CI:0.9–2.3) and brain (RR=1.8, 95% CI:0.7–4.8), and null findings for cancers of the lung and stomach.</P><P><B>Conclusions</B></P><P>Our findings provide additional evidence that occupational lead exposure increases risk of meningioma.</P>