Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

Abstract

Recent European data facilitate an epidemiological investigation of the controversial cannabis–cancer relationship. Of particular concern were prior findings associating high-dose cannabis use with reproductive problems and potential genetic impacts. Cancer incidence data age-standardised to the world population was obtained from the European Cancer Information System 2000–2020 and many European national cancer registries. Drug use data were obtained from the European Monitoring Centre for Drugs and Drug Addiction. Alcohol and tobacco consumption was sourced from the WHO. Median household income was taken from the World bank. Cancer rates in high-cannabis-use countries were significantly higher than elsewhere (β-estimate = 0.4165, p = 3.54 × 10−115). Eighteen of forty-one cancers (42,675 individual rates) were significantly associated with cannabis exposure at bivariate analysis. Twenty-five cancers were linked in inverse-probability-weighted multivariate models. Temporal lagging in panel models intensified these effects. In multivariable models, cannabis was a more powerful correlate of cancer incidence than tobacco or alcohol. Reproductive toxicity was evidenced by the involvement of testis, ovary, prostate and breast cancers and because some of the myeloid and lymphoid leukaemias implicated occur in childhood, indicating inherited intergenerational genotoxicity. Cannabis is a more important carcinogen than tobacco and alcohol and fulfills epidemiological qualitative and quantitative criteria for causality for 25/41 cancers. Reproductive and transgenerational effects are prominent. These findings confirm the clinical and epidemiological salience of cannabis as a major multigenerational community carcinogen.

Role of Cannabinoids in Oral Cancer

“…In the initial studies, tobacco smoking and alcohol were identified as cofactors. Recent research has identified significant associations between cannabis use and various malignant disorders, including oropharyngeal cancer [96]. Cannabis is a stronger carcinogen than tobacco or alcohol, with the concentration of the phytocannabinoid THC playing a key role [96].…”

“…Recent research has identified significant associations between cannabis use and various malignant disorders, including oropharyngeal cancer [96]. Cannabis is a stronger carcinogen than tobacco or alcohol, with the concentration of the phytocannabinoid THC playing a key role [96]. Other studies do not support a direct association or even suggest potential anti-cancer effects of cannabinoids in oral cancer [101,110,111].…”

“…Cannabis has been proven to be a stronger carcinogen compared to tobacco or alcohol. The primary factor associated with cannabis and its impact on cancer was found to be the concentration of the phytocannabinoid THC in the cannabis plant [96]. A different research study presents proof supporting a clear connection between smoking cannabis and a higher likelihood of developing laryngeal cancer [97].…”

Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1–aging and epigenomics

“…The unequivocal demonstration that cellular dedifferentiation occurs due to DNA demethylation, weakening of superenhancers and superanchors, aberrant promoter–enhancer communication, and retrotransposon activation clearly explains why many diverse tissues are primed by cannabis for malignant transformation, which addresses the issue of why so many cancers have been epidemiologically linked with cannabis ( 25 , 28 , 32 , 179 – 188 , 220 , 234 – 247 ). Cancers that were linked with cannabis exposure in Europe were all cancers, excluding non-melanoma skin cancer, bladder, brain, breast, colorectal, Hodgkin's, kidney, larynx, liver, lung, melanoma, multiple myeloma, myeloid and lymphoid leukemias, non-Hodgkin's lymphoma, and esophagus, oropharynx, ovary, pancreas, prostate, stomach, testis, thyroid, and uterine cervix cancers ( 189 ).…”

“…For these reasons, it is envisaged that the triple confluence of rising cannabis prevalence rates, intensity of use rates, and cannabinoid potency will manifest relatively abruptly as steep rises in adverse mental health, as well as teratologic, carcinogenic, and age-related outcomes, as are indeed being observed and documented in several jurisdictions ( 16 , 25 , 27 – 32 , 179 – 187 , 189 – 205 , 207 , 232 , 234 – 237 , 321 , 342 – 345 ).…”