The Association Among Environmental Chemicals Exposure,Genome-Wide DNA Methylation,And Risk Of Childhood Acute Lymphocytic Leukemia

Objective This study aims to investigate the association among the exposure of environmental chemicals, genome-wide DNA methylation change(epigenetic modifications) and risk of childhood acute lymphocytic leukemia(c ALL), and then provides a fundamental basis for primary prevention of c ALL.Methods A case-control study of cALL was conducted in children who have been selected according to the diagnostic standard in Shenzhen Children`s Hospital, China from Jan. 2015 to Jan. 2016. And the control was selected in the same hospital. Questionnaire was conducted on children’s parents, and collected the urine and EDTA blood from children. Then we quantitative measured the internal dose of formaldehyde(formaldehyde-human serum albumin) by using enzyme-linked immunosorbent assay,measured the metabolic product of benzene,toluene and xylene(trans、trans-muconic acid, hippuric acid, 2-, 3-, 4- methylhippuric acid). by using high performance liquid chromatography(HPLC), and the determination date were corrected by urine creatinine. Meanwhile, we examined the genome-wide DNA methylation in whold blood in each individual by using immuno fluorescence method.Result(1) The qusetionnaire of environmental risk factors: In the study, 71 cases were collected(average age was 6.075±3.610 years old, and 63.38% of male), 142 controls(average age was 5.908±3.573 years old) were 1:2 matched with the cases on gender and age(±1.0 years old). The results of self-reported show that home paint in the past 10 years(P=0.001), maternal chemical exposure during pregnancy(P=0.014), paternal diesel or gasoline exposure(P<0.001), paternal dye exposure(P=0.014) and trash burning near the residence(P=0.032) were associated with an increased risk of c ALL.(2) Quantitative analysis of formaldehyde, benzene, toluene and xylene: the positive detection rate of only benzene in the cases was significantly higher than this in the control(P<0.01), with other internal dose of exposure were similar in cases and controls. Median of formaldehyde and benzene concentrations in the cases(32.120pg/ml, 2.505μg/g Cr) were significantly higher than those in the controls(18.705pg/ml, 0.672μg/g Cr)(P<0.05).Multiple logistic regression analysis showed that higher level of tt-MA(OR=1.090,95%CI:1.003-1.185)was associated with an increase risk of c ALL.(3) Analysis of genome-wide DNA methylation change: results showed the level of genome-wide DNA methylation in the cases was lower compared to the controls. The factor of genome-wide DNA methylation was no into the multiple logistic regression which environmental chemical factor were controled.Conclusion(1) c ALL is caused by multiple factors, of which environmental chemical exposure was one of the important factor.(2) benzene exposure may be associated with the increase risk of c ALL.(3) the level of genome-wide DNA methylation in the cases was lower than the controls.