Acute lymphoid leukaemia (ALL) is the commonest childhood cancer whose incidence is rising in many nations. In the USA, between 1975 and 2016, ALL rates (ALLRs) rose 93.51% from 1.91 to 3.70/100,000 < 20 years. ALL is more common in Caucasian-Americans than amongst minorities. The cause of both the rise and the ethnic differential is unclear, however, prenatal cannabis exposure was previously linked with elevated childhood leukaemia rates. We investigated epidemiologically if cannabis use impacted nationally on ALLRs, its ethnic effects, and if the relationship was causal. State data on overall, and ethnic ALLR from the Surveillance Epidemiology and End Results databank of the Centre for Disease Control (CDC) and National Cancer Institute (NCI) were combined with drug (cigarettes, alcoholism, cannabis, analgesics, cocaine) use data from the National Survey of Drug Use and Health; 74.1% response rate. Income and ethnicity data was from the US Census bureau. Cannabinoid concentration was from the Drug Enforcement Agency Data. Data was analyzed in R by robust and spatiotemporal regression. In bivariate analyses a dose-response relationship was demonstrated between ALLR and Alcohol Use Disorder (AUD), cocaine and cannabis exposure, with the effect of cannabis being strongest (β-estimate = 3.33(95%C.I. 1.97, 4.68), P = 1.92 × 10− 6). A strong effect of cannabis use quintile on ALLR was noted (Chi.Sq. = 613.79, P = 3.04 × 10− 70). In inverse probability weighted robust regression adjusted for other substances, income and ethnicity, cannabis was independently significant (β-estimate = 4.75(0.48, 9.02), P = 0.0389). In a spatiotemporal model adjusted for all drugs, income, and ethnicity, cannabigerol exposure was significant (β-estimate = 0.26(0.01, 0.52), P = 0.0444), an effect increased by spatial lagging (THC: β-estimate = 0.47(0.12, 0.82), P = 0.0083). After missing data imputation ethnic cannabis exposure was significant (β-estimate = 0.64(0.55, 0.72), P = 3.1 × 10− 40). 33/35 minimum e-Values ranged from 1.25 to 3.94 × 1036 indicative of a causal relationship. Relaxation of cannabis legal paradigms had higher ALLR (Chi.Squ.Trend = 775.12, P = 2.14 × 10− 112). Cannabis legal states had higher ALLR (2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000, P = 5.05 × 10− 10). Data show that ALLR is associated with cannabis consumption across space-time, is associated with the cannabinoids, THC, cannabigerol, cannabinol, cannabichromene, and cannabidiol, contributes to ethnic differentials, demonstrates prominent quintile effects, satisfies criteria for causality and is exacerbated by cannabis legalization.

中文翻译：

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大麻素暴露是美国儿科急性淋巴白血病发病率的主要驱动因素：结合地理空间、多重插补和因果推断研究

急性淋巴细胞白血病 (ALL) 是最常见的儿童癌症，其发病率在许多国家都在上升。在美国，从 1975 年到 2016 年，ALL 率 (ALLRs) 从 1.91 上升到 3.70/100,000 < 20 年，上升了 93.51%。ALL 在白人美国人中比在少数民族中更常见。上升和种族差异的原因尚不清楚，但是，产前大麻暴露以前与儿童白血病发病率升高有关。我们从流行病学上调查了大麻的使用是否在全国范​​围内对 ALLR 产生影响、其种族影响，以及这种关系是否是因果关系。来自疾病控制中心 (CDC) 和国家癌症研究所 (NCI) 的监测流行病学和最终结果数据库的总体和种族 ALLR 数据与药物（香烟、酗酒、大麻、镇痛药、可卡因）使用数据来自全国药物使用和健康调查；74.1% 的响应率。收入和种族数据来自美国人口普查局。大麻素浓度来自缉毒局数据。通过稳健和时空回归在 R 中分析数据。在双变量分析中证明了 ALLR 与酒精使用障碍 (AUD)、可卡因和大麻暴露之间存在剂量反应关系，其中大麻的影响最强（β 估计值 = 3.33（95%CI 1.97, 4.68），P = 1.92 × 10− 6)。注意到大麻使用五分位数对 ALLR 的强烈影响（Chi.Sq. = 613.79，P = 3.04 × 10− 70）。在针对其他物质、收入和种族进行调整的逆概率加权稳健回归中，大麻具有独立显着性（β 估计值 = 4.75（0.48, 9.02），P = 0.0389）。在针对所有药物调整的时空模型中，收入和种族，大麻素暴露是显着的（β-估计值 = 0.26（0.01, 0.52），P = 0.0444），空间滞后效应增加（THC：β-估计值 = 0.47（0.12, 0.82），P = 0.0083） . 在缺失数据插补后，种族大麻暴露是显着的（β 估计值 = 0.64（0.55, 0.72），P = 3.1 × 10− 40）。33/35 的最小 e 值范围从 1.25 到 3.94 × 1036，表明存在因果关系。放宽大麻法律范式具有更高的 ALLR（Chi.Squ.Trend = 775.12，P = 2.14 × 10− 112）。大麻合法州的 ALLR 较高（2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000，P = 5.05 × 10− 10）。数据显示 ALLR 与跨时空的大麻消费有关，与大麻素、四氢大麻酚、大麻酚、大麻酚、大麻二酚和大麻二酚有关，有助于种​​族差异，