Reece Albert Stuart, Hulse Gary Kenneth
Division of Psychiatry, University of Western Australia, Crawley, WA, 6009, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, 6027, Australia.
Arch Public Health. 2022 Mar 30;80(1):99. doi: 10.1186/s13690-022-00811-8.
The genotoxic and cancerogenic impacts of population-wide cannabinoid exposure remains an open but highly salient question. The present report examines these issues from a continuous bivariate perspective with subsequent reports continuing categorical and detailed analyses.
Age-standardized state census incidence of 28 cancer types (including "All (non-skin) Cancer") was sourced using SEER*Stat software from Centres for Disease Control and National Cancer Institute across US states 2001-2017. It was joined with drug exposure data from the nationally representative National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental Health Services Administration 2003-2017, response rate 74.1%. Cannabinoid data was from Federal seizure data. Income and ethnicity data sourced from the US Census Bureau. Data was processed in R.
Nineteen thousand eight hundred seventy-seven age-standardized cancer rates were returned. Based on these rates and state populations this equated to 51,623,922 cancer cases over an aggregated population 2003-2017 of 124,896,418,350. Regression lines were charted for cancer-substance exposures for cigarettes, alcohol use disorder (AUD), cannabis, THC, cannabidiol, cannabichromene, cannabinol and cannabigerol. In this substance series positive trends were found for 14, 9, 6, 9, 12, 6, 9 and 7 cancers; with largest minimum E-Values (mEV) of 1.76 × 10, 4.67 × 10, 2.74 × 10, 4.72, 2.34 × 10, 2.74 × 10, 1.90 × 10, 5.05 × 10; and total sum of exponents of mEV of 34, 32, 13, 0, 103, 58, 25, 31 indicating that cannabidiol followed by cannabichromene are the most strongly implicated in environmental carcinogenesis. Breast cancer was associated with tobacco and all cannabinoids (from mEV = 3.53 × 10); "All Cancer" (non-skin) linked with cannabidiol (mEV = 1.43 × 10); pediatric AML linked with cannabis (mEV = 19.61); testicular cancer linked with THC (mEV = 1.33). Cancers demonstrating elevated mEV in association with THC were: thyroid, liver, pancreas, AML, breast, oropharynx, CML, testis and kidney. Cancers demonstrating elevated mEV in relation to cannabidiol: prostate, bladder, ovary, all cancers, colorectum, Hodgkins, brain, Non-Hodgkins lymphoma, esophagus, breast and stomach.
Data suggest that cannabinoids including THC and cannabidiol are important community carcinogens exceeding the effects of tobacco or alcohol. Testicular, (prostatic) and ovarian tumours indicate mutagenic corruption of the germline in both sexes; pediatric tumourigenesis confirms transgenerational oncogenesis; quantitative criteria implying causality are fulfilled.
人群广泛接触大麻素对基因毒性和致癌性的影响仍是一个有待解决但极为突出的问题。本报告从连续双变量的角度审视这些问题，后续报告将继续进行分类和详细分析。
使用SEER*Stat软件从疾病控制中心和美国国立癌症研究所获取2001 - 2017年美国各州28种癌症类型（包括“所有（非皮肤）癌症”）的年龄标准化发病率。将其与药物滥用和精神健康服务管理局在2003 - 2017年每年进行的具有全国代表性的药物使用和健康全国调查中的药物暴露数据相结合，回应率为74.1%。大麻素数据来自联邦缉获数据。收入和种族数据来自美国人口普查局。数据在R语言中进行处理。
返回了19877个年龄标准化癌症发病率。根据这些发病率和各州人口，这相当于在2003 - 2017年总计124896418350人的人群中有51623922例癌症病例。绘制了香烟、酒精使用障碍（AUD）、大麻、四氢大麻酚（THC）、大麻二酚（CBD）、大麻色烯、大麻酚和大麻萜酚的癌症 - 物质暴露回归线。在这个物质系列中，分别发现14种、9种、6种、9种、12种、6种、9种和7种癌症呈正相关趋势；最小E值（mEV）最大的分别为1.76×10、4.67×10、2.74×10、4.72、2.34×10、2.74×10、1.90×10、5.05×10；mEV指数总和分别为34、32、13、0、103、58、25、31，表明大麻二酚其次是大麻色烯与环境致癌作用关联最为密切。乳腺癌与烟草和所有大麻素相关（mEV = 3.53×10）；“所有癌症”（非皮肤）与大麻二酚相关（mEV = 1.43×10）；儿童急性髓系白血病与大麻相关（mEV = 19.61）；睾丸癌与四氢大麻酚相关（mEV = 1.33）。与四氢大麻酚相关且mEV升高的癌症有：甲状腺癌、肝癌、胰腺癌、急性髓系白血病、乳腺癌、口咽癌、慢性髓系白血病、睾丸癌和肾癌。与大麻二酚相关且mEV升高的癌症有：前列腺癌、膀胱癌、卵巢癌、所有癌症、结直肠癌、霍奇金淋巴瘤、脑癌、非霍奇金淋巴瘤、食管癌、乳腺癌和胃癌。
数据表明包括四氢大麻酚和大麻二酚在内 的大麻素是重要的社区致癌物，其影响超过烟草或酒精。睾丸癌、（前列腺癌）和卵巢肿瘤表明两性生殖系的诱变破坏；儿童肿瘤发生证实了跨代肿瘤发生；满足了暗示因果关系 的定量标准。
