Decoding the genetic links between substance use disorder and cancer vulnerability.

OBJECTIVE

Cancer remains a leading cause of mortality and morbidity worldwide, imposing a significant public health burden. While cannabis and opioids are widely used in cancer pain management, their potential for abuse and addiction has raised concerns regarding their long-term health effects, including possible associations with cancer risk. However, the relationship between substance use disorders (SUDs) and cancer susceptibility remains controversial. This Mendelian randomization (MR) study aimed to investigate the potential causal effects of cannabis use disorder (CUD) and opioids use disorder (OUD) on cancer vulnerability.

METHODS

We conducted a two-sample MR study using summary statistics from genome-wide association studies, including data from FinnGen and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW), complemented by a range of sensitivity analyses to assess the robustness of the findings.

RESULTS

IVW analysis identified 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 yielded directionally consistent results. Reverse MR analysis provided no statistically significant evidence supporting a causal effect of these cancers on OUD (all P > 0.05). Additionally, no evidence of a significant causal relationship was observed between CUD and any cancer type (P > 0.05).

CONCLUSIONS

This study suggests a potential causal link between OUD and increased susceptibility to bladder cancer, acute myeloid leukemia, and ovarian cancer, warranting further investigation in larger, multi-ethnic population studies. These results contribute to the ongoing discourse on the long-term health impacts of substance use disorders and highlight the need for further research to elucidate their potential oncogenic effects.