Researchers have discovered that bladder cells in men are more prone to selective growth of dangerous mutations even before bladder cancer develops, with smoking being a significant factor in cancer progression.

The study was conducted by researchers from the University of Washington in the United States and the Institutional Research Council in Barcelona, Spain. Its results were published in the journal Nature on October 8 and covered by EurekAlert.

Bladder cancer is one of the most common types of cancer worldwide. Men are nearly four times more likely to develop it than women, and smoking is the main known environmental risk factor.

Cancer does not develop overnight. Over decades, mutations accumulate in tissue cells, and some clones gain an advantage that allows them to grow faster than others. This study shows these differences are already evident in healthy tissue before the disease appears.

The researchers analyzed bladder samples from 45 donors, detecting thousands of mutations and quantifying them.

Smoking Stimulates Mutations

Dr. López-Pigas, a researcher at the Catalan Institution for Research and Advanced Studies and leader of the biomedical genomics group at the Institutional Research Council Barcelona, explains: “Many mutations accumulate in healthy tissue throughout life, but what matters is not just their number, but which ones succeed in outgrowing others and expand into clones—copies of the same cell carrying the same mutations.”

He adds, “We observed that smoking and biological sex directly influence this process.”

The researchers noted clear biological differences between men and women. Some mutations in cancer-related genes found in male donors gave the cells carrying them an advantage to expand even in healthy bladder tissue.

They also observed a significant effect of smoking. Among donors over 55 years old, those with a history of smoking had a high proportion of mutations in the TERT promoter, a DNA element that reactivates telomerase, allowing cells to avoid aging and continue dividing.

This work provides evidence that tobacco not only causes new mutations but also acts as a clonal promoter, facilitating the expansion of cells with pre-existing mutations.