Wang Xinran, Zhong Charlie, Ma Xiaomei, Metayer Catherine, Mancuso Nicolas, Gauderman W James, Wiemels Joseph L
Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
American Cancer Society, Atlanta, Georgia.
Cancer Epidemiol Biomarkers Prev. 2025 Jan 9;34(1):100-107. doi: 10.1158/1055-9965.EPI-24-1037.
Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. Tobacco exposure during gestation has been investigated as a potential risk factor, but its role remains undefined. Given tobacco's toxicologic profile as a DNA-damaging agent, we examined the impact of DNA repair gene variability as a source of vulnerability to tobacco exposure risk for ALL.
Leveraging demographic and genotype data from two large California-based ALL epidemiology studies, we used logistic regression, MinimumP (minP) statistical method, and permutation tests to examine interactions between DNA repair genes and prenatal tobacco exposure.
We found statistically significant interactions between prenatal tobacco exposure and DNA repair genes RECQL (minP = 1.00 × 10-4, FDR-P value = 1.86 × 10-2) and TDG (minP = 1.00 × 10-4, FDR-P value = 1.86 × 10-2) with regard to childhood ALL risk. Notable interactions in the homologous recombination pathway were observed among Latino children, whereas non-Latino White children displayed significant interactions in the base excision repair and nucleotide excision repair pathways.
Our study highlights the significance of DNA repair genes and pathways when evaluating environmental exposure to tobacco smoke, suggesting that genetic variability within these pathways could impact vulnerability in the development of childhood ALL.
This study highlights the significant impact of genetic variation interacting with prenatal tobacco exposure on ALL risk. Further research is needed to understand these interactions and their implications for ALL etiology. Expanding studies to other gene-environment interactions will aid in developing targeted prevention, diagnosis, and treatment strategies for pediatric oncology.
急性淋巴细胞白血病（ALL）是儿童中最常见的癌症类型。孕期接触烟草已被作为一种潜在风险因素进行研究，但其作用仍不明确。鉴于烟草作为一种DNA损伤剂的毒理学特性，我们研究了DNA修复基因变异性作为ALL易受烟草暴露风险影响的一个来源所产生的影响。
利用来自加利福尼亚州两项大型ALL流行病学研究的人口统计学和基因型数据，我们使用逻辑回归、最小P值（minP）统计方法和置换检验来研究DNA修复基因与产前烟草暴露之间的相互作用。
我们发现产前烟草暴露与DNA修复基因RECQL（minP = 1.00×10⁻⁴，FDR - P值 = 1.86×10⁻²）和TDG（minP = 1.00×10⁻⁴，FDR - P值 = 1.86×10⁻²）在儿童ALL风险方面存在统计学上的显著相互作用。在同源重组途径中，拉丁裔儿童中观察到显著的相互作用，而非拉丁裔白人儿童在碱基切除修复和核苷酸切除修复途径中表现出显著的相互作用。
我们的研究突出了在评估环境烟草烟雾暴露时DNA修复基因和途径的重要性，表明这些途径内的基因变异性可能会影响儿童ALL发生发展中的易感性。
本研究突出了基因变异与产前烟草暴露相互作用对ALL风险的重大影响。需要进一步研究以了解这些相互作用及其对ALL病因学的影响。将研究扩展到其他基因 - 环境相互作用将有助于制定针对儿科肿瘤学的靶向预防、诊断和治疗策略。
