Initially Probing Into The Risk Assessment System Of BaP Resulting In Lung Cancer Based On Biology Markers

Purpose: By establishing the microcosmic risk assessment system of BaP based on molecule markers, forecasting the early scathe of people at some concentration of BaP, discussing the risk of the biology markers of early scathe from some environment factors and genetic factors, serving as a base of probing the mechanisms of mutation, abnormality and cancer of BaP and providing a base for the microcosmic risk assessment system and the mechanisms of other polycyclic aromatic hydrocarbons.Data Source and Method: 1. The secondary data: Searching the literatures about BaP and using the secondary data to establish the models. The method of the risk assessment of the polymorphisms of CYP1A1 and GSTM1 in Chinese people to lung cancer is Meta analysis. The dose-response models among molecule markers of the early scathe are set up with the method of BMD. 2. The original data of experiments: Supplied by Pro Zheng Yuxin, the department of occupation sanitation and poison of the Chinese CDC. We Used path analysis to establish the models of the response from the environment factors and genetic factors to the molecule markers of the early scathe.Results: 1.The results of Meta analysis: (1) The polymorphisms of MspI of CYP1A1: In the fourteen literatures, the exposure groups are all type B and C of MspI. Through heterogeneity test, the Chi-square value is 36.26, degree of freedom is 13 and the p value is 0.0005, so analyzing with random effect model. The union odds ratio is 1.37 and the 95% confidence interval is from 1.09 to 1.72. By total test, Z value is 2.67, p value is 0.008, so the model is significant in statistics. (2)The polymorphisms of Exon7 of CYP1A1: In the nine literatures, the exposure groups are all Ile/Val and Val/Val. Through heterogeneity test, the Chi-square value is 9.72, degree of freedom is 8 and the p value is 0.29, so analyzing with fixed effect model. The union odds ratio is 1.69 and the 95% confidence interval is from 1.39 to 2.06. By total test, Z value is 5.22, p value is less than 0.00001, so the model is significant in statistics. (3)The polymorphisms of GSTM1: In the fifteen literatures, the exposure groups are all null type of GSTM1 (-/-). Through heterogeneity test, the Chi-square value is 17.26, degree of freedom is 14 and the p value is 0.24, so analyzing with fixed effect model. The union odds ratio is 1.57 and the 95% confidence interval is from 1.37 to 1.81. By total test, Z value is 6.31, p value is less than 0.00001, so the model is significant in statistics. 2. The polynomial models set up with BMD: (1) BaP→DNA addition: The experiment is mensurating the concentration of DNA addition in human bronchial epithelial cell (BEAS-2B) after treated with five different concentration BaP for 24 hours. Through testing, there is the dose-response relationship between BaP and DNA addition. The polynomial model is DNA addition(/108 nucleotide)=0.40-0.08×BaP-1.79×10-5×BaP2. (2) BaP→DNA scathe integral: The experiment used the human lung adenocarcinoma cells (A549) as objects. Mensurating the concentration of DNA scathe integral after treated with different concentration BaP for 6 hours. Through testing, there is the dose-response relationship between BaP and DNA scathe integral. The polynomial model is DNA scathe integral=9.31+5.15×BaP-0.16×BaP2. (3) BaP→SCE, MN: After in vitro exposure the human blood lymphocytes to different concentration BaP, counting the SCE and MN number. The polynomial model is: SCE=1.56×ln(BaP)+38.02, MN=3.84×ln(BaP)+77.60. 3. The path analysis models: (1) 1-hydroxide guanosine(Hydcre): The factors that influence the quantity of 1-hydroxide guanosine are coke worker or not, type of work, smoke or not, the polymorphism of CYP1A1 and GSTM1. The influence degree is coke worker or not > type of work > smoke or not > the polymorphism of CYP1A1 > the polymorphism of GSTP1. (2) Comet Olive (Olive): The factors that influence the quantity of Comet Olive are the quantity of 1-hydroxide guanosine, coke worker or not, type of work, smoke or not, XRCC1_exon6 polymorphism and ERCC2_exon6 polymorphism. The influence degree is coke worker or not > the quantity of 1-hydroxide guanosine > type of work > XRCC1_exon6 polymorphism > smoke or not > ERCC2_exon6 polymorphism. (3) Microkernel number (MNi): The factors that influence the Microkernel number are the quantity of 1-hydroxide guanosine, Comet Olive, coke worker or not, type of work, age, smoke or not. The influence degree is coke worker or not > type of work > Comet Olive > age > the quantity of 1-hydroxide guanosine > smoke or not. And theConclusion: 1. The risk of type B and C of CYP1A1 MspI is 37% higher than type A. The risk of Ile/Val and Val/Val of CYP1A1 Exon7 is 69% higher than Ile/Ile. The null type of GSTM1 is 57% higher than positive type. 2. The exposure markers and effect markers all have the relationship of dose-response with BaP. So we could estimate the concentration of markers in vivo exposed by BaP according to the models we have set up. 3. The most influencing factors of effect markers are coke worker or not and the type of work. It mentions that BaP exposure is one of the most important causes of high effect markers. So we could choose high risk people of occupational lung cancer according to the polymorphism of those enzymes and PAHs concentration in the working atmosphere. And then move them to other workaround of low PAHs concentration and mainly give them occupational protection to decrease them the risk of lung cancer.