Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
School of Public Health, University of California, Berkeley, Berkeley, California.
Cancer Epidemiol Biomarkers Prev. 2023 Dec 1;32(12):1707-1715. doi: 10.1158/1055-9965.EPI-23-0258.
Associations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual-level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California.
Maternal exposure to tobacco smoke was assessed with a validated methylation marker (cg05575921) of the aryl hydrocarbon receptor repressor (AHRR) gene in newborn dried blood spots. We adjusted for sex, birthweight, gestational age, mode of delivery, year of birth, AHRR quantitative trait locus (mQTL) rs77111113, and a polygenetic risk score for childhood ALL. We additionally adjusted for principal components in a gene-environment interaction testing method that incorporates gene-only and environment-only effects along with interactions.
AHRR hypomethylation overall was not associated with childhood ALL. In gene-environment interaction testing, several genetic variants displayed significant interaction with AHRR hypomethylation and childhood ALL.
Our results suggest that novel candidates in PTPRK and DPP6 may play a role in tobacco-related leukemogenesis. Further research is necessary to better understand the effects of tobacco and these variants on childhood ALL risk.
Despite the lack of an overall "main effect," tobacco exposure during pregnancy affects childhood ALL risk depending on specific genetic variants.
母亲在怀孕期间吸烟与儿童急性淋巴细胞白血病（ALL）之间的关联结果不一。这可能是由于自我报告的吸烟存在偏差，或个体水平的危险因素存在其他差异。我们利用一种生物标志物来评估母亲在怀孕期间的吸烟暴露、遗传因素与加利福尼亚州两项大型儿童 ALL 病例对照研究中儿童后续 ALL 风险之间的关联。
采用经证实的芳香烃受体阻遏物（AHRR）基因的甲基化标志物（cg05575921）评估母亲在新生儿期的吸烟暴露情况。我们对性别、出生体重、胎龄、分娩方式、出生年份、AHRR 数量性状基因座（mQTL）rs77111113 以及儿童 ALL 多基因风险评分进行了调整。我们还通过基因-环境相互作用测试方法进行了主成分调整，该方法结合了基因-仅环境和环境-仅效应以及相互作用。
AHRR 低甲基化总体上与儿童 ALL 无关。在基因-环境相互作用测试中，几个遗传变异与 AHRR 低甲基化和儿童 ALL 之间存在显著的相互作用。
我们的研究结果表明，PTPRK 和 DPP6 中的新候选基因可能在与烟草相关的白血病发病机制中发挥作用。需要进一步的研究来更好地了解烟草和这些变异对儿童 ALL 风险的影响。
尽管没有总体“主效应”，但母亲在怀孕期间的吸烟暴露会根据特定的遗传变异影响儿童 ALL 的风险。
