基因环境分析揭示了与产前烟草暴露的新遗传候选人,与儿童急性淋巴细胞白血病的风险相关
Charlie Zhong1, Shaobo Li1, Katti Arroyo1
1Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
概括
孕妇在怀孕期间接触烟草可能会增加儿童急性淋巴细胞白血病 (ALL) 的风险,但这种影响取决于特定的遗传变异. 需要进一步的研究来理解这些基因环境相互作用在白血病发生.
科学领域:
- 环境表观遗传学环境表观遗传学
- 儿科瘤学 儿科瘤学
- 遗传流行病学遗传流行病学
背景情况:
- 怀孕期间母亲吸烟是儿童急性淋巴细胞白血病 (ALL) 的潜在危险因素,但之前的研究显示结果不一致.
- 自我报告的吸烟数据可能带来偏见,需要客观措施来准确评估风险.
- 研究生物标志物和遗传因素可以阐明产前暴露和儿童白血病之间的复杂关系.
研究的目的:
- 为了评估孕妇在怀孕期间和童年期间暴露于烟草烟雾之间的关系,使用生物标记物评估ALL风险.
- 探索遗传变异在改变母亲吸烟暴露对儿童ALL的影响中的作用.
- 为了确定特定的基因和参与烟草相关的白血病发生的途径.
主要方法:
- 通过在新生儿干血斑点中的碳化合物受体抑制剂 (AHRR) 基因中验证的甲基化标志物 (cg05575921) 评估母亲的烟草暴露.
- 统计分析调整了多个共同变量,包括性别,出生体重,妊娠年龄和遗传因素,如AHRR mQTL和ALL的多基因风险得分.
- 进行了基因环境相互作用测试,结合了基因单独,环境单独的影响,以及它们的相互作用.
主要成果:
- 总体而言,AHRR低甲基化与儿童ALL风险没有显著关联.
- 基因环境相互作用分析显示,特定遗传变异,AHRR低甲基化和儿童ALL之间存在显著的关联.
- 这表明,母亲吸烟对ALL风险的影响取决于个人的遗传构成.
结论:
- 这些发现表明,孕妇在怀孕期间接触烟草会以遗传依赖的方式影响儿童ALL风险.
- 包括PTPRK和DPP6在内的新型候选基因可能与烟草相关的白血病发生有关.
- 需要进一步的研究,以充分了解烟草暴露,遗传变异和儿童ALL发育的相互作用.
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