Geospatiotemporal and causal inference study of cannabis and other drugs as risk factors for female breast cancer USA 2003-2017

Breast cancer (BC) is the commonest human cancer and its incidence (BC incidence, BCI) is rising worldwide. Whilst both tobacco and alcohol have been linked to BCI genotoxic cannabinoids have not been investigated. Age-adjusted state-based BCI 2003-2017 was taken from the Surveillance Epidemiology and End Results database of the Centers for Disease Control. Drug use from the National Survey of Drug Use and Health, response rate 74.1%. Median age, median household income and ethnicity were from US census. Inverse probability weighted (ipw) multivariable regression conducted in R. In bivariate analysis BCI was shown to be significantly linked with rising cannabis exposure {beta-est. = 3.93 [95% confidence interval 2.99, 4.87], P = 1.10 x 10(-15)}. At 8 years lag cigarettes:cannabis [beta-est. = 2660 (2150.4, 3169.3), P = 4.60 x 10(-22)] and cannabis:alcoholism [beta-est. = 7010 (5461.6, 8558.4), P = 1.80 x 10(-17)] were significant in ipw-panel regression. Terms including cannabidiol [CBD; beta-est. = 16.16 (0.39, 31.93), P = 0.446] and cannabigerol [CBG; beta-est. = 6.23 (2.06, 10.39), P = 0.0034] were significant in spatiotemporal models lagged 1:2 years, respectively. Cannabis-liberal paradigms had higher BCI [67.50 +/- 0.26 v. 65.19 +/- 0.21/100 000 (mean +/- SEM), P = 1.87 x 10(-11); beta-est. = 2.31 (1.65, 2.96), P = 9.09 x 10(-12)]. 55/58 expected values >1.25 and 13/58 >100. Abortion was independently and causally significant in space-time models. Data show that exposure to cannabis and the cannabinoids Delta 9-tetrahydrocannabinol, CBD, CBG and alcoholism fulfil quantitative causal criteria for BCI across space and time. Findings are robust to adjustment for age and several known sociodemographic, socio-economic and hormonal risk factors and establish cannabinoids as an additional risk factor class for breast carcinogenesis. BCI is higher under cannabis-liberal legal paradigms.