甲醛接触、全基因组DNA甲基化与儿童急性淋巴细胞白血病关系

Association of formaldehyde exposure,genome-wide DNA methylation,and childhood acute lymphocytic leukemia

目的探讨甲醛接触、全基因组DNA甲基化与儿童急性淋巴细胞白血病(cALL)发病关系。方法采用病例-对照研究的方法,以59例cALL患儿为病例组,以54例骨折患儿为对照组。分别采用酶联免疫法、免疫荧光法测定研究对象血样中人甲醛血清白蛋白结合物(FA-HAS)水平和血液全基因组DNA甲基化水平。结果病例组患儿血液中FA-HAS水平高于对照组(中位数:59.61 vs 35.06 fg/L,P<0.01)。病例组患儿全基因组DNA甲基化水平低于对照组[(2.86±0.31)vs(3.00±0.28),P<0.05]。甲醛接触水平与全基因组DNA甲基化不相关(Spearman相关系数=-0.18,P>0.05)。FA-HAS水平高、全基因组DNA低甲基化均是cALL发病的危险因素(P<0.05)。结论甲醛接触水平较高、全基因组DNA低甲基化者,cALL发病风险较高。

Objective To explore the relationship of formaldehyde exposure, genome-wide DNA methylation, and prevalence of childhood acute lymphocytic leukemia（ cALL）.Methods A case-control study was conducted.Fifty-nine newly diagnosed cALL patients were selected as case group,and 54 orthopedic patients were included in control group.Enzyme-linked immunosorbent assay was used to measure the level of formaldehyde-human serum albumin（ FA-HSA） and immunofluorescence method was used to examine the genome-wide DNA methylation level in whole blood.Results The level of FA-HAS in the blood of the case group was higher than that in the control group（ median： 59.61 vs 35.06 fg/L,P〈0.01）.Genomic-wide DNA methylation level in the case group was lower than that in the controls[（ 2.86 ± 0.31） vs（ 3.00 ± 0.28）,P〈0.05].Formaldehyde exposure level was not associated with genomic-wide DNA methylation（ Spearman correlation coefficient =-0.18,P〉0.05）.High FA-HAS level and hypomethylation of genomic-wide DNA were risk factors for cALL onset（ P〈0.05）.Conclusion Patients with high level of formaldehyde exposure and hypomethylation of genomic-wide DNA have a high risk of cALL.