| Objective To explore the association among the exposure of environmental chemicals,plasma mi RNA change and risk of childhood acute lymphocytic leukemia(c ALL),and analyze the role of the interaction between the two factors for the risk of c ALL,then provides a fundamental basis for primary prevention of c ALL.Methods A hospital-based case-control study was conducted.111 pairs of newly diagnosed c ALL patients and orthopedic patients were collected from Shenzhen Children's Hospital,China,from January 2015 to November 2016,Age and sex of case and control were 1:1 matched.A questionnaire including population data and environment exposure features was conducted,c ALL patients with clinical diagnosis information was also collected.LNATM mi RNA microarray was performed using 4 pairs of c ALL and controls selected from the sample population.The expression level of plasma mi RNA was validated by real time quantitative PCR.Conditional Logistic regression analysis was applied to analysis the relationship between the exposure of environmental chemicals and mi RNA expression levels on c ALL.The receiver operating characteristic curve(ROC)analysis and reclassification analysis were also conducted to assess the feasibility of mi RNAs serving as biomarkers for c ALL.The interaction of environmental chemicals exposure with mi RNA was analyzed by crossover analysis,and relative excess risk of interaction(RERI),attributable proportion(AP)of interaction and synergy index(S)was applied to evaluate the additive interaction of the two factors.Results ? 111 cases were collected(average age was 5.19 ± 3.18 years old,and 62.16% of male),111 controls(average age was 5.08 ± 3.19 years old)were 1:1matched with the cases on gender and age(<±1.0 years old).Multiple Logistic regression analysis show that children chemical substances' exposure(P=0.014)and father chemical substances' exposure(P=0.022),family history of cancer(P=0.021),children habitable room paint exposure(P=0.006)were associated with an increased risk of c ALL.? The expression levels of plasma let-7f-5p?mi R-5100 and mi R-25-3p in the c ALL patients were significantly lower than those of the controls(P<0.01).After adjusting for confounding factors,3 mi RNA remained significantly associated with the occurrence of c ALL(OR and 95%CI were 0.84(0.76-0.92)?0.81(0.74-0.91)and 0.81(0.73-0.89),respectively.Results of the ROC analysis and reclassification analysis showed that introduction of one or more mi RNA to traditional risk factors significantly improved the area under the curve(P<0.05)and provide additional values to diagnosis(P<0.01).? After adjusting the confounding factors,in the gene-environment interaction,the association of decreased expression of let-7f-5p with father chemical substances' exposure having an increased risk of c ALL(OR=13.31,95%CI:2.65~66.85),and there was a multiplied interaction between the two factors(OR =6.66,95%CI:1.41~31.33).Those carrying decreased expression of let-7f-5p and children's room paint exposure having an increased risk compared to those that carrying nothing risk factor patients(OR=13.40,95%CI:3.41~52.68),and there was a multiplied interaction between let-7f-5p with children's room paint exposure on the risk of c ALL might exist(OR =6.69,95%CI:1.87~23.94).The association of decreased expression of mi R-5100 with father chemical substances' exposure having an increased risk of c ALL(OR=16.84,95%CI:3.43~82.80),and there was a multiplied interaction between the two factors(OR =8.24,95%CI:1.79~37.88).Those carrying decreased expression of mi R-5100 and children's room paint exposure having an increased risk compared to those that carrying nothing risk factor patients(OR=16.44,95%CI:4.19~64.59),and there was a multiplied interaction between mi R-5100 with children's room paint exposure on the risk of c ALL might exist(OR =7.63,95%CI:2.15~27.10).The association of decreased expression of mi R-25-3p with father chemical substances' exposure having an increased risk of c ALL(OR=11.55,95%CI:2.33~57.23),and there was a multiplied interaction between the two factors(OR =6.58,95%CI:1.40~30.92).Those carrying decreased expression of mi R-25-3p and children's room paint exposure having an increased risk compared to those that carrying nothing risk factor patients(OR=11.64,95%CI:2.99~45.27),and there was a multiplied interaction between mi R-25-3p with children's room paint exposure on the risk of c ALL might exist(OR =6.63,95%CI:1.85~23.86).The additive interaction not existed between children's chemical exposure,father chemical exposure with the three plasma mi RNA(let-7f-5p,mi R-5100 and mi R-25-3p),respectively,but existed between children's room paint exposure with the three plasma mi RNA(let-7f-5p,mi R-5100 and miR-25-3p).Conclusion ? Children chemical substances' exposure and father chemical substances' exposure,family history of cancer,Children habitable room paint exposure were the main risk factors for the c ALL.? The lower expression levels of plasma let-7f-5p,mi R-5100,mi R-25-3p were associated with the incidence rate of c ALL.? Environmental chemicals exposure,mi RNA abnormal expression are combined effect to increase the risk of cALL. |
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