Sociodemographically Stratified Exploration of Pancreatic Cancer Incidence in Younger US Patients: Implication of Cannabis Exposure as a Risk Factor

Abstract

Introduction. The aetiology for the recent increase in pancreatic cancer incidence (PCI) in the US is unknown. This paper provides an epidemiological investigation of the exponential increase in PCI in young people aged 15–34 years, particularly amongst females, with a focus on the exponential rise amongst African American females, and its relationship to substance use. Methods. National pancreatic cancer data from recent reports. Tobacco, alcohol and daily cannabis use data taken from the annual nationally representative National Survey of Drug Use and Health, response rate = 74%. Results. Amongst the 15–34-year-aged cohort, PCI was found to be significantly more common in females (females: β-est. = 0.1749 p = 0.0005). African American females are noted to have the highest rates of daily cannabis use amongst females in the 26–34 and 35–49-year groups. The relationship between PCI and daily cannabis use was strongly positive across all ethnicities and in both sexes. In African American females, the Pearson correlation between daily cannabis use and PCI was R = 0.8539, p = 0.0051. In an additive multivariable model for each sex and race, cannabis was the only significant term remaining in the final model in the 15–34-year-aged cohort and thus out-performed alcohol as a risk factor. The most significant term in multivariate models was the alcohol:cannabis interaction which was highly significant in all ethnicities from p = 2.50 × 10−7 for Caucasian American females and the highest E-value pair was for Hispanic American females (E-value estimate = 1.26 × 10102 and E-value lower bound 2.20 × 1074). Conclusion. These data show that cannabis fulfills quantitative criteria of causality in all age, sex and ethnicity cohorts, and thus explains both the recent surge in PCI and its ethnocentric predominance. Cannabis interacts powerfully genotoxically and cancerogenically with alcohol, with increases in cannabis use driving the current PCI surge. These results raise the important question as to how much cannabis might be responsible for the modern renaissance in cancer rates amongst younger people.

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

“…The use of cannabis by young females is also rising rapidly, including during pregnancy. Based upon these and similar results, it would appear that cannabis use is an important community cancerogenic risk factor, which has likely been overlooked in public health discussions to the time of writing [ 227 , 228 ].…”

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 ).…”

“…Importantly, cannabis has been shown to be a driver of rising rates of breast, testicular, liver and pancreatic cancers in adults ( 28 , 183 , 184 , 187 , 190 , 234 , 253 – 255 ) and of total pediatric cancer ( 188 ) and acute lymphoid leukemia ( 188 ) in children. Most of the studies referred to in this paragraph were conducted in space–time contexts and in causal inferential paradigms to allow for the formal quantitative investigation of epidemiologically causal pathways to be investigated.…”

“…Indeed, a question has been formally posed ( 190 , 234 ) regarding whether cannabis might be a major factor underlying the modern resurgence of several types of cancer developing in patients younger than 50 years ( 235 ).…”

“…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 ).…”