Decoding the Genetic Links Between Substance Use Disorder and Cancer Vulnerability

Abstract

Abstract Background Cancer is a leading cause of mortality and morbidity globally and burdens public health heavily. Cannabis and opioids are promising applications for cancer pain management. However, due to their widespread abuse and addiction potential, they have become the focus of public health attention. They may have critical long-term health effects, raising concerns about their possible association with cancer risk. However, their relationship with cancer vulnerability is highly controversial. This Mendelian randomization (MR) study aimed to investigate the causal relationship of cannabis use disorder (CUD) and opioids use disorder (OUD) on cancer vulnerability. Methods Two-sample MR study using summary statistics from genome-wide association studies (GWAS), FinnGen, and UK Biobank. The primary method was inverse-variance weighted (IVW), and we included a range of sensitivity analyses to assess the robustness of the findings. Findings: We found the IVW results showed a causal association between OUD and bladder cancer (OR = 1.040, 95% CI 1.004–1.078, P = 0.029, adj. P = 0.125), acute myeloid leukemia (OR = 0.931, 95% CI 0.885–0.978, P = 0.005, adj. P = 0.061) and ovarian cancer (OR = 0.937, 95% CI 0.891–0.984, P = 0.010, adj. P = 0.064). Sensitivity analysis is directionally consistent with IVW. In the reverse MR analysis, none of the methods produced statistically significant proof of a connection between OUD and three cancers (all P > 0.05). However, OUD did not prove a genetic causal relationship with other cancers (P > 0.05). We found no relevant evidence of a statistically significant potential causal effect of CUD on cancers (P > 0.05). Summary: This study suggests that OUD may be causally linked to bladder, AML, and ovarian cancer, which needs to be further evaluated in extensive population studies.