Division of Psychiatry, University of Western Australia, Crawley, Western Australia, 6009, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia.
BMC Cancer. 2021 Sep 3;21(1):984. doi: 10.1186/s12885-021-08598-7.
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). A strong effect of cannabis use quintile on ALLR was noted (Chi.Sq. = 613.79, P = 3.04 × 10). 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). 33/35 minimum e-Values ranged from 1.25 to 3.94 × 10 indicative of a causal relationship. Relaxation of cannabis legal paradigms had higher ALLR (Chi.Squ.Trend = 775.12, P = 2.14 × 10). Cannabis legal states had higher ALLR (2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000, P = 5.05 × 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.
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呈上升趋势。在美国，1975 年至 2016 年间，ALL 发病率（ALLR）从每 10 万<20 岁人群 1.91 上升到 3.70，上升了 93.51%。白种美国人和少数民族相比，ALL 更为常见。上升和种族差异的原因尚不清楚，然而，先前有研究表明产前大麻暴露与儿童白血病发病率升高有关。我们通过调查研究，从疾病控制与预防中心（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中获取了全国范围内 ALLR 的种族数据，同时结合了来自国家药物使用和健康调查的毒品（香烟、酗酒、大麻、止痛药、可卡因）使用数据；该调查的回复率为 74.1%。收入和种族数据来自美国人口普查局。大麻素浓度来自毒品执法局的数据。使用 R 软件进行稳健和时空回归分析。
在双变量分析中，ALLR 与酒精使用障碍（AUD）、可卡因和大麻暴露呈剂量反应关系，大麻的作用最强（β 估计值=3.33（95%CI 1.97，4.68），P=1.92×10）。大麻使用五分位数对 ALLR 的影响也很强（卡方检验=613.79，P=3.04×10）。在调整了其他物质、收入和种族的逆概率加权稳健回归中，大麻是独立显著的（β 估计值=4.75（0.48，9.02），P=0.0389）。在调整了所有药物、收入和种族的时空模型中，大麻二醇的暴露具有显著影响（β 估计值=0.26（0.01，0.52），P=0.0444），这种影响随着空间滞后而增加（THC：β 估计值=0.47（0.12，0.82），P=0.0083）。在进行缺失数据插补后，种族间大麻暴露仍具有显著影响（β 估计值=0.64（0.55，0.72），P=3.1×10）。35 个最小 e 值中有 33 个在 1.25 到 3.94×10 之间，表明存在因果关系。放松大麻法律范式会导致更高的 ALLR（卡方趋势检验=775.12，P=2.14×10）。大麻合法化的州 ALLR 更高（2.395±0.039 比 2.127±0.008/100,000，P=5.05×10）。
数据表明，ALLR 与大麻消费在时空上相关，与大麻素 THC、大麻二醇、大麻酚、大麻色烯、大麻二酚有关，导致了种族差异，表现出明显的五分位效应，符合因果关系的标准，并且大麻合法化加剧了这种差异。
