环境化学物暴露与儿童急性淋巴细胞白血病风险的关联研究

Association of exposure to environmental chemicals with risk of childhood acute lymphocytic leukemia

目的：探讨环境化学物暴露与儿童急性淋巴细胞白血病（cALL）之间的关联性。方法采用病例-对照研究的方法，收集2015年1月—2016年1月深圳市儿童医院就诊于血液肿瘤科的儿童病例，按年龄和性别进行1∶2匹配，招募就诊于骨科的调查对象作为对照组。通过问卷调查获取儿童及其家长的基本信息资料以及环境暴露特征，并采集儿童的血液、尿液标本。采用ELISA测定血清中甲醛的内暴露物（人-甲醛白蛋白结合物）的浓度；采用高效液相色谱法（HPLC）测定尿液中苯、甲苯、二甲苯的内暴露物（反-反式黏糠酸、马尿酸、2-、3-、4-甲基马尿酸）的浓度。采用多因素logistic回归模型分析儿童及其父母暴露因素与cALL发病的关系。结果共收集新发cALL病例71例，年龄为（6.08±3.61）岁，对照142名，年龄为（5.91±3.57）岁。环境化学暴露因素的问卷调查结果显示，10年内居所油漆（OR=4.39，95%CI：1.87~10.31）、母亲孕期暴露化学物（OR=11.78，95%CI：1.65~83.88）、父亲暴露柴油/汽油（OR=8.15，95%CI：2.68~24.83）、父亲暴露染发剂等染料（OR=7.77，95%CI：1.52~39.67）、垃圾焚烧（OR=6.08，95%CI：1.17~31.66）是cALL的危险因素；化学物内暴露方面，病例组中苯的内暴露物检出率（91%，40/44）高于对照组（73%，81/111），差异有统计学意义（χ2=5.92，P=0.021）。病例组中甲醛、苯的内暴露浓度的P50（分别为32.120 pg/ml和2.505μg/g肌酐）高于对照组（分别为18.705 pg/ml和0.672μg/g肌酐），差异有统计学意义（Z值分别为-1.98和-3.95，P值分别为0.047、〈0.001）。多因素logistic回归模型分析结果显示，苯暴露（OR=1.09，95%CI：1.00~1.19）、10年内居所油漆暴露（OR=3.56，95%CI：1.20~10.53）、父亲汽油/柴油暴露（OR=3.75，95%CI：1.06~13.22）是cALL发病的危险因素。结论苯等多种环境化学因素的暴露可能增加cALL的发病风险。

Objective This study aimed to investigate the association between exposure to environmental chemicals and the risk of childhood acute lymphocytic leukemia （cALL）. Methods A case-controlled study was conducted in Shenzhen Children＇s Hospital, China from January 2015 to January 2016. The cases were selected from the section of Hematology and Oncology, and the controls were selected from Orthopedics by 1∶2 matching of cases according to sex and age. A questionnaire including population data and chemical exposure characteristics was conducted on the children＇s parents, and urine and EDTA-blood were collected from the children. Then, we quantitatively measured the internal dose of formaldehyde （i.e., formaldehyde-human serum albumin） by enzyme-linked immunosorbent assay and the doses of metabolites benzene, toluene, and xylene （i.e., trans-muconic acid, hippuric acid, and methylhippuric acid） by high-performance liquid chromatography. Logistic regression models were used to＆amp;nbsp;analyze the relationships between exposure factors measured from children and their parents and cALL. Results In the study, 71 cases （average age：6.08 ± 3.61 years）, and 142 controls （average age：5.91 ± 3.57 years） were assessed; there were no differences in general demographics between two groups. The self-reported results showed that living in a home that had been painted in the past 10 years （OR=4.39, 95% CI： 1.87-10.31）, maternal chemical exposure during pregnancy （OR=11.78, 95% CI： 1.65-83.88）, paternal diesel or gasoline exposure （OR=8.15, 95% CI： 2.68-24.83）, paternal dye exposure （OR=7.77, 95% CI： 1.52-39.67） and trash burning near the child＇s residence （OR=6.08, 95% CI： 1.17-31.66） were associated with increased risk of cALL. The positive detection rates of only benzene metabolites were significantly higher in cases （40/44） than controls （81/111） （χ2=5.92, P=0.021）. The median formaldehyde and benzene concentrations in cases （32.120 pg/ml, 2.505 μg/gCr） were significantly higher than those in controls （18.705 pg/ml, 0.672μg/gCr;Z values：-1.98 and-3.95, P values：0.047 and〈0.001, respectively）. Multiple logistic regression analysis showed that benzene exposure （OR=1.09, 95% CI： 1.00-1.19）, home painting in the past 10 years （OR=3.56, 95%CI：1.20-10.53） and paternal diesel or gasoline exposure （OR=3.75, 95% CI： 1.06-13.22） were associated with increased risk of cALL. Conclusion A variety of environmental chemistry factors, such as benzene exposure, increase the risk of cALL, and further studies are warranted to explore their specific roles.