Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003–2017: part 1 – continuous bivariate analysis

Abstract

Background 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. Methods 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. Results 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 × 109, 4.67 × 108, 2.74 × 104, 4.72, 2.34 × 1018, 2.74 × 1017, 1.90 × 107, 5.05 × 109; 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 × 109); “All Cancer” (non-skin) linked with cannabidiol (mEV = 1.43 × 1011); 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. Conclusion 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.

Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study

“…The full implications of this profound and far-reaching result have yet to be fully explored. They have an obvious relevance and concordance with the results reported both in this study and in similar reports [27,[79][80][81][96][97][98]. Several classical studies have provided clear evidence of chromosomal breaks [9,10,13], end-to-end fusions [9,10], and chromosomal bridge formations in telophase [11,12,99] following cannabis exposure.…”

“…The link between cancer and cannabinoids is complex and multifactorial and has recently been reviewed in several recently published works [10,[14][15][16]27,31,32,34,35,[41][42][43]71,72,75,[78][79][80][81][82][83][84][85][86][87][88][89][90][91][92]. Our intention here is to introduce the way in which these general observations may relate to some specific cancer types.…”

European Epidemiological Patterns of Cannabis- and Substance-Related Body Wall Congenital Anomalies: Geospatiotemporal and Causal Inferential Study

“…As outlined in the introduction, the mechanisms of cannabis genotoxicity are many and complex and have been reviewed elsewhere [ 4 , 5 , 6 , 7 , 16 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. For our present purposes, we wish to focus on two pathways of particular importance, these being the disruption of key morphogen gradients and the epigenomic perturbations.…”

Letter to the editor on “Geotemporospatial and causal inferential epidemiological overview and survey of USA cannabis, cannabidiol and cannabinoid genotoxicity expressed in cancer incidence 2003–2017, parts 1–3”

“…A three-part study by Reece and Hulse [ 1 ] that associated cannabis with a causal role to cancer has recently been published. Though it uses reputable American datasets and multiple analysis models that meet foundational epidemiological standards, the claim of causal inferences linking cannabis to cancer is unsubstantiated.…”

“…It is also concerning, out of 28 cancer types explored, the authors applied their strongest statistical method to only two – prostate and ovarian. Plus, like all statistical tests, E-values and IPW should be used as additional assessments of evidence [ 3 , 4 ], and cannot confidently “imply causality” [ 1 ].…”