Certain genes involved in how cells process sugar for energy may influence the risk of bladder cancer, according to a large genetic study published recently in Biochemistry and Biophysics Reports.
Researchers identified AK3, PFKM, PFKP and CHST4 as glycolysis-related candidates associated with bladder cancer risk, with the strongest genetic support observed for PFKM at the protein level. Although the findings are not yet definitive, they point to metabolic pathways that could eventually guide new prevention or treatment strategies.
Bladder cancer has long been linked to altered energy use in tumor cells. Cancer cells often rely heavily on glycolysis, a process that converts glucose into energy and produces lactate.
To explore whether inherited differences in glycolysis-related genes affect bladder cancer risk, investigators analyzed 300 genes using Mendelian randomization and summary-based Mendelian randomization, methods that use large amounts of data on genetic variants to determine their connection to a disease. They relied on large genetic datasets from FinnGen R12 and the U.K. Biobank.
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In the Mendelian randomization analysis, only AK3, ALDH2 and PFKP had enough valid genetic markers for testing. While AK3-mediated lactate levels initially showed a possible association with bladder cancer risk, further analysis found this link was too weak to provide strong evidence of a connection.
“Among the candidates, PFKM emerges as the most genetically supported signal, based on protein-level association and colocalization, whereas AK3, PFKP, and CHST4 show proxy-dependent or non-colocalized associations that should be interpreted cautiously,” explained the authors of this research.
When researchers examined gene expression data, AK3 expression was associated with lower bladder cancer risk, while PFKP expression was associated with higher risk. None of these findings remained significant after false discovery rate correction and no shared genetic signal was confirmed through colocalization analysis.
At the protein level, PFKM showed a positive association with bladder cancer risk, and demonstrated colocalization support with a posterior probability of 0.606, suggesting a shared genetic basis. In contrast, CHST4 protein levels were associated with reduced risk in two cohorts, but lacked colocalization evidence and were not replicated.
For patients, these findings do not immediately change screening or treatment. Instead, they help scientists better understand how altered energy metabolism may contribute to bladder cancer development. Over time, confirming these genetic links could support new drug targets aimed at slowing tumor growth by disrupting cancer cells’ energy supply.
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