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Relationship Between Environmental Risk Factors, Genetic Polymorphisms And Adult Acute Leukemia

Posted on:2005-09-19Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhangFull Text:PDF
GTID:2144360152467208Subject:Occupational and Environmental Health
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Environmental and genetic factors are commonly considered to jointly result in cancers. A matched case-control study has been carried out to explore the possible relationship between environmental risk factors, genetic polymorphisms of metabolic enzyme, receptor, DNA repair genes and adult acute leukemia in Chinese Han population. The polymorphisms of the genes were genotyped by PCR-RFLP analysis. Conditional logistic regression model was applied to screen 14 possible environmental risk factors and to analyze the interaction between environmental risk factors and genetic polymorphisms to adult acute leukemia. The principle results were as follows: Epidemiology study on environmental risk factors to adult acute leukemia. A paired case-control study was performed to screen the 14 possible risk factors such as pollution around the inhabitancy, oral history of chloromycetin, exposure history of x-ray, exposure history of organic solvents, history of hair dye use, house decoration history in 135 cases and 135 controls from Chinese Han population of Jiangsu province. According to the preceding data on epidemiology, the results show pollution around the inhabitancy (OR:4.499,95%CI: 1.856~10.905), occupational exposure history of organic solvents (OR:2.564,95%CI:1.028~6.391), the moving interval after house decoration (OR:1.672,95%CI:1.170~2.390), the years of oxidant hair dye use (OR:1.679,95%CI:1.044~2.699) were four of the environmental risk factors to adult acute leukemia analyzed by conditional multiple regression model (α=0.05). Summary population attribute risk (PAR) of the above four was 0.5502. The risk of the moving interval after house decoration in three months was 1.672 times of that over three months. The risk of the oxidant hair dye use over five years was 1.679 times of that in five years. Further analysis showed pollution around the inhabitancy, occupational exposure history of organic solvents, the years of oxidant hair dye use were the environmental risk factors of acute myelocytic leukemia (AML) and the Summary PAR was 0.4201. The risk of the oxidant hair dye use over five years was 1.830 times of that in five years. The risk factor of acute lymphocytic leukemia (ALL) was the moving interval after house decoration and its adjusted PAR was 0.2970. 2. The relationship between the polymorphism of genes and susceptibility to adult acute leukemiaThe genetic polymorphisms of 7 metabolic enzyme, receptor and DNA repair genes of CYP1A1, GSTT1, GSTM1, NQO1, P2X7 A1513C, XRCC1, XPD were genotyped by PCR-RFLP analysis in peripheral blood DNA samples from both cases and controls. The normal genotypes frequency of CYP1A16235 C/C,C/T,T/T were 49.5%,37.6%,13.9%; GSTT1-,GSTM1- were 38.6%,33.3%; NQO1609 C/C,C/T,T/T were 44.5%,42.4%,13.1%; P2X71513 A/A,A/C,C/C were 82.8%, 16.2 %, 1.0%; XRCC1399 Arg/ Arg,Arg/ Gln,Gln/ Gln were 55.6%, 37.4%, 7.0%; XPD751Lys/Lys,Lys/Gln,Gln/Gln were 81.4%,15.7%,2.9%. CYP1A1, GSTT1, P2X7, XPD were susceptible genes of adult acute leukemia and the susceptible genotypes were CYP1A1 6235C/T ,T/T; GSTT1(-), P2X7 1513C/A,C/C; XPD 751 Lys /Gln, Gln/Gln, respectively. The CYP1A1 was susceptible gene for AML, The CYP1A1 and XPD were susceptible genes for ALL. The interaction between CYP1A16235 and XRCC1399 mutant genotypes was found to have synergistic effect to the occurrence of acute leukemia which provided the evidence of significantly higher susceptibility to acute leukemia in individuals with two mutant genotypes of CYP1A16235 and XRCC1399 than with only one of the two mutant genotype , So was P2X71513 and XRCC1399. 3. The interaction between environmental risk factors and genetic polymorphisms in the occurrence of adult acute leukemia The interaction between environmental risk factors and genetic polymorphisms was analyzed by unconditional multiple logistic regression model. The significant interactions of synergistic effect between CYP1A16235 mutant genotype and occupational exposure history of organic solvents (OR=16.868, P=0.0304) or oxidant hai...
Keywords/Search Tags:environmental risk factor, oxidant hair dye, house decoration pollution, genetic polymorphism, case-control study, interaction, acute leukemia
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