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To explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design.152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30 single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions.Based on logistic regression, the main effects of GSTP1 rs947894, EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P = 0.06). There existed 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6 rs1135840.Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

To explore the relationship between genetic polymorphisms of CYP-1A1 and CYP2D6 and risks of chronic benzene poisoning (BP).A case control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were involved. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technology was used for detecting the single nucleotide polymorphisms (SNPs) of MspI in the non-coding region of CYP-1A1 gene and c.188, g.212 position in the first extron of CYP2D6 gene.The individuals with CYP1A1 MspI T/T genotype had a 1.32 times (95% CI: 1.05 approximately 1.65, P = 0.02) increased risk of BP compared with those carrying T/C and C/C genotypes. In no-smoking population, there was a 1.56 times (95% CI: 1.15 approximately 2.12, P = 0.003) increased risk of BP for subjects carrying CYP1A1 MspIT/T genotype compared with those carrying T/C and C/C genotypes. The individuals carrying CYP2D6 c.188 C/C or C/T genotype had a 1.23 times (95% CI: 1.05 approximately 1.42, P = 0.01) increased risk compared with those carrying T/T genotypes. In no-smoking population, there was a 1.23 times (95% CI: 1.04 approximately 1.47, P = 0.01) increased risk of BP for subjects carrying CYP2D6 c.188 C/C or C/T genotypes compared with those carrying T/T genotype. The single nucleotide polymorphism of g.212 position in the first extron of CYP2D6 gene had not been validated.The individuals with CYP2D6 c.188 C/C, CYP2D6 c.188 C/T and CYP1A1 MspIT/T genotypes tend to be more susceptible to benzene toxicity.

To explore the relationship between genetic polymorphisms in hMTH1, hOGG1 and hMYH and risks of chronic benzene poisoning (CBP).A case control study was conducted. One hundred and fifty-two BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. The polymerase chain reaction restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.83 of hMTH1 gene, c.326 of hOGG1 gene and c.335 of hMYH gene.There were 2.51 times (OR(adj) = 2.51, 95% CI: 1.14-5.49, P = 0.02) and 2.49 times (OR(adj) = 2.49, 95% CI: 1.52-4.07, P0.01) risks of BP for individuals carrying genotypes of hMTH1c.83Val/Met + Met/Met or hOGG1c.326Cys/Cys compared with individuals carrying genotypes of hMTH1c.83Val/Val or hOGG1c.326Ser/Cys + Ser/Ser, respectively. Compared with individuals carrying genotypes of hOGG1c.326Cys/Cy and hMYHc.335 is/His at the same time, there was 0.33 times (OR(adj) = 0.33, 95% CI = 0.15-0.72, P = 0.01) risks of BP for these with genotypes of hOGG1c.326Ser/Cys + Ser/Ser and hMYHc.335His/Gln + Gln/Gln simultaneously. In the smoking group, there was 0.15 times (OR(adj) = 0.15, 95% CI: 0.03-0.68, P = 0.01) risks of BP for subjects carrying genotypes of hMYHc.335His/Gln + Gln/Gln compared with these carrying genotypes of hMYHc.335His/His.Polymorphisms of hMTH1 Val83 Met and hOGG1 Ser326Cys may contribute to altered risks of CBP, and potential interaction may exist among polymorphisms of hOGG1 Ser326Cys and hMYH His335Gln.

To explore the association between genetic polymorphisms of XRCC1 and susceptibility to acute childhood leukemia.A case-control study with 63 childhood leukemia patients and 66 control subjects was conducted to investigate the role of three XRCC1 polymorphisms (c. 194, c. 280 and c. 399 ) on susceptibility to childhood leukemia. Genotyping was performed using Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) to detect the single nucleotide polymorphisms (SNPs) of XRCC1 gene.There was a 2.235-fold increased risk of childhood leukemia for individuals carrying XRCC1c. 399 Gin allele (95% CI 1.038 - 4.812) compared with subjects carrying Arg/Arg allele, and the OR among boys was 3.110 (95% CI 1.235 - 7.831). No interaction was found between X-ray exposure and XRCC1 polymorphisms using Logistic regression analysis.Polymorphism of XRCC1 gene may contribute to the higher risk of childhood leukemia.

To explore the effects of interaction between environmental exposure factors and genetic polymorphism in toxicant metabolizing enzymes on risk of occupational chronic benzene poisoning.One hundred and fifty-two cases of chronic benzene poisoning were analyzed for the risk by case-only study.The frequency of non-null GSTT1 gene in benzene poisoning workers with moderate benzene exposure level was higher than that in cases with lower benzene exposure (68.63% vs 38.00%, OR(adj) = 4.32, 95% CI 1.75 - 10.66, P = 0.002). The frequency of NQO1 C.609T/T gene in alcohol drinking group was higher than that in non-drinking group (61.11% vs 20.00%, OR(adj) = 8.03, 95% CI 2.28 - 28.25, P = 0.001), moreover, it was higher in workers with smoking and drinking than that in the rest group, and in drinking x exposure level workers than that in non-drinking x exposure level workers (85.71% vs 22.76%, OR(adj) = 18.62, 95% CI 2.01 - 172.72, P = 0.01 and 61.11% vs 20.00%, OR(adj) = 3.18, 95% CI 1.55 - 6.52, P = 0.002 respectively). The frequency of non-null GSTM1 gene was also higher in drinking x exposure level workers than that in non-drinking x exposure level workers (66.67% vs 47.06%, OR(adj) = 1.99, 95% CI 1.05 - 3.76, P = 0.036).There is interaction between the polymorphism of GSTT1 gene and moderate benzene exposure level; non-null GSTM1 gene and drinking x exposure level increase the risk of occupational chronic benzene poisoning; polymorphism of NQO1 gene C.609 also interacts with drinking, while polymorphism of NQO1 gene and drinking x smoking may further increase the risk of occupational chronic benzene poisoning.

To explore the relationship between genetic polymorphisms of microsomal epoxide hydrolase (mEH) and susceptibility of chronic benzene poisoning (BP).A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.113 and c.139 of mEH gene.The risk of BP for individuals carrying mEHc.113 C/C genotype was 0.60 (OR = 0.60, 95% CI: 0.37 - 0.97, P = 0.04) of those carrying T/T and T/C genotypes. In non-smoking population, the risk of BP for subjects carrying mEHc.113 C/C genotype was 0.56 (OR = 0.56, 95% CI: 0.33 - 0.96, P = 0.03) of those carrying T/T and T/C genotypes, and in non-drinking population, the individuals carrying mEHc.113 C/C genotype was 0.51 (OR = 0.51, 95% CI: 0.30 - 0.86, P = 0.01) of those carrying T/T and T/C genotypes.The subjects carrying mEHc.113 C/C genotype and together with non-smoking or non-drinking habit may have lower risk of chronic benaene poisoning.