Genetic analysis revealed that type 2 diabetes and higher glycated hemoglobin levels may be linked to a reduced risk of certain skin cancers, according to a recent study.
In a Mendelian randomization study, published in Frontiers in Medicine, investigators assessed the causal relationship between type 2 diabetes (T2D), glycated hemoglobin (HbA1c), and the risk of skin cancer, including melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma. The investigators analyzed genetic data from the UK Biobank, DIAMANTE consortium, and FinnGen, evaluating both disease risk and the impact of antidiabetic drug targets.
Higher HbA1c levels were linked to a potential reduction in melanoma risk (odds ratio [OR] = 0.886, 95% confidence interval [CI] = 0.792–0.991, P = .0347). Similarly, genetic liability to T2D was associated with a lower risk of BCC (OR = 0.960, 95% CI = 0.928–0.992, P = .0147). However, perturbation of the SLC5A2 gene, a target of sodium-glucose cotransporter 2 inhibitors, was associated with an increased risk of BCC (OR = 2.004, 95% CI = 1.270–3.161, P = .0027). This finding was not corroborated by colocalization analysis.
No statistically significant associations were identified between other antidiabetic drug targets such as dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists and skin cancer risk. Additionally, no links were observed between drug target gene expression and skin cancer.
The findings suggested associations between T2D, HbA1c, and specific skin cancer subtypes. However, further research is needed to validate these results in diverse populations and to investigate potential mechanisms.
These results highlighted the utility of genetic methods in investigating disease associations, emphasizing the need for further research into metabolic and cancer-related pathways.
The study had several limitations, including the focus on lifetime drug exposure through MR estimates, which may not align with the shorter action timeframe of drugs, and the inability to evaluate off-target effects of certain antidiabetic drug targets. Additionally, discrepancies between MR and colocalization results, limited statistical power, and the exclusive use of a European population restricted generalizability and underscored the need for further investigation in diverse populations and with additional genetic and environmental considerations.
Full disclosures can be found in the published study.
