Journal: BMC medicine
This study used large-scale GWAS data to investigate shared genetic architecture between psychoactive substance use (specifically alcohol and nicotine dependence) and various cancers.
Key points:
- The authors cross-referenced genome-wide association summary statistics for substance use phenotypes and multiple cancer types.
- They identified 34 substance use–cancer trait pairs with significant genetic correlations using LDSC and HDL approaches.
- In total, 97 pleiotropic genomic risk loci were found that influenced both substance use and cancer risk.
- Many of the implicated loci mapped to 109 genes with enriched expression in the cerebellum, including 21 “hub” genes showing cross-trait pleiotropy.
- Mendelian randomization analyses supported causal effects of alcohol use dependence and nicotine use dependence on cancer risk, consistent with epidemiologic data.
- A phenome-wide association study was used to screen these pleiotropic genes for potential safety issues if pharmacologically inhibited.
- After excluding genes with high predicted risk of adverse effects, three genes emerged as potentially safer, druggable targets: CHRNA2, HRH3, and PTK6.
Overall, the work suggests that shared cerebellar genetic networks underlie both substance use liability and cancer susceptibility and highlights specific molecular targets that may have therapeutic relevance at the PSU–cancer interface.