Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, California.
Cancer Epidemiol Biomarkers Prev. 2021 Aug;30(8):1517-1525. doi: 10.1158/1055-9965.EPI-21-0009. Epub 2021 May 21.
Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the gene and increased frequency of somatic gene deletions among ALL cases.
Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data. Multivariable Poisson regression models were used to test the associations between the epigenetic biomarkers and gene deletion numbers.
We found an association between DNA methylation at CpG cg05575921 and deletion number among 284 childhood B-ALL cases with MethylationEPIC array data, with a ratio of means (RM) of 1.31 [95% confidence interval (CI), 1.02-1.69] for each 0.1 value reduction in DNA methylation, an effect size similar to our previous report in an independent set of 198 B-ALL cases with 450K array data [meta-analysis summary RM (sRM) = 1.32; 95% CI, 1.10-1.57]. The polyepigenetic smoking score was positively associated with gene deletion frequency among all 482 B-ALL cases (sRM = 1.31 for each 4-unit increase in score; 95% CI, 1.09-1.57).
We provide further evidence that prenatal tobacco-smoke exposure may influence the generation of somatic copy-number deletions in childhood B-ALL.
Analyses of deletion breakpoint sequences are required to further understand the mutagenic effects of tobacco smoke in childhood ALL.
父母吸烟与急性淋巴细胞白血病（ALL）的发病机制有关，ALL 是最常见的儿童癌症。我们最近报道了基因上的一个早期生命烟草烟雾暴露的表观遗传生物标志物与 ALL 病例中体细胞基因缺失频率增加之间的关联。
在这里，我们使用在加利福尼亚儿童白血病研究中可用的 Illumina 450K 或 MethylationEPIC 阵列数据的 482 例 B 细胞急性淋巴细胞白血病（B-ALL）病例的一个扩展集，进一步评估了这种关联的两个母体妊娠期间吸烟的表观遗传生物标志物 - CpG cg05575921 处的 DNA 甲基化和最近建立的多表观遗传吸烟评分。多变量泊松回归模型用于测试表观遗传生物标志物与基因缺失数量之间的关联。
我们发现 CpG cg05575921 处的 DNA 甲基化与 MethylationEPIC 阵列数据中 284 例儿童 B-ALL 病例的缺失数量之间存在关联，DNA 甲基化每降低 0.1 个值，平均值比（RM）为 1.31[95%置信区间（CI），1.02-1.69]，这一效应大小与我们之前在独立的 198 例 B-ALL 病例的 450K 阵列数据中报告的结果相似[元分析汇总 RM（sRM）=1.32；95%CI，1.10-1.57]。多表观遗传吸烟评分与所有 482 例 B-ALL 病例的基因缺失频率呈正相关（评分每增加 4 个单位，sRM=1.31；95%CI，1.09-1.57）。
我们提供了进一步的证据表明，产前烟草烟雾暴露可能会影响儿童 B-ALL 中体细胞拷贝数缺失的产生。
需要分析缺失断点序列，以进一步了解烟草烟雾在儿童 ALL 中的诱变作用。
