Scientists Uncover Cellular Mechanism Behind Bladder Cancer's Higher Risk in Men

A groundbreaking study published in the journal Nature on October 8, 2025, has unveiled a surprising cellular trigger for bladder cancer, shedding new light on why the condition is significantly more prevalent in men. Researchers from the Institute for Research in Biomedicine (IRB Barcelona) and the University of Washington have demonstrated that both smoking and biological sex profoundly influence how normal cells in healthy bladder tissue evolve, promoting the expansion of mutated cells that are crucial for cancer development. This discovery offers a deeper understanding of a disease that affects over 10,000 Britons annually and is up to four times more common among men.

cancer.org reported, The research pinpoints the expansion of specific mutated cell clones within healthy bladder tissue as a key factor. While healthy tissues naturally accumulate mutations over a lifetime, the critical insight from this study is not merely the number of mutations, but which ones gain an evolutionary advantage and proliferate.

This clonal expansion, particularly in certain cancer-related genes, was observed to be more pronounced in male donors, providing a biological explanation for the long-standing disparity in bladder cancer incidence between sexes.

news-medical.net noted, Dr. Núria López-Bigas and Dr. Abel González-Pérez at IRB Barcelona, alongside Dr. Rosana Risques at the University of Washington, led the collaborative effort. Their findings reveal distinct biological differences between men and women at a cellular level. Specifically, in male bladders, mutations in genes linked to cancer exhibited a greater capacity for expansion.

Furthermore, the study highlighted a significant impact of smoking, with donors over 55 who had a history of smoking showing a high frequency of mutations in the TERT promoter, a genetic element that enables cells to bypass aging and continue dividing unchecked.

bcan.org reported, This pivotal research, conducted as part of team PROMINENT under the prestigious Cancer Grand Challenges initiative, aims to answer fundamental questions about early tumor development. The insights gained could revolutionize risk prediction and prevention strategies for bladder cancer.

The ability to measure these expanding clones in the bladder may eventually lead to new diagnostic tools, such as non-invasive urine sample analysis, offering earlier detection and improved patient outcomes.

• cancer.org noted, Bladder cancer remains a significant global health concern, with the American Cancer Society (ACS) estimating approximately 84,870 new cases in the United States for 2025. Of these, about 65,080 are projected to be in men and 19,790 in women, underscoring the substantial gender disparity.

  The ACS also predicts a 2.2% overall increase in bladder cancer cases in 2025, with a concerning 3.1% rise anticipated for men, while cases among women are expected to decline by 1.6%.

• news-medical.net reported, Historically, the higher incidence of bladder cancer in men has been attributed to factors like greater exposure to smoking and industrial chemicals. Earlier research also suggested a role for the androgen receptor, a protein more active in men, in the disease's development.

  While these factors remain relevant, the new findings provide a deeper cellular-level explanation for the observed differences.

• bcan.org noted, The core of the recent discovery lies in understanding cellular evolution within healthy tissues. While mutations are a natural part of aging, the study emphasizes that the critical factor is not just the presence of mutations, but which specific mutations manage to outgrow others and form expanding clones.

  This process, influenced by both biological sex and smoking, sets the stage for potential malignant transformation.

• cancer.org reported, The implications for future medical practice are substantial. By identifying these early cellular changes and the mechanisms driving clonal expansion, researchers hope to develop more precise risk prediction models.

  This could pave the way for innovative early detection methods, potentially including non-invasive urine tests that can identify individuals at higher risk long before overt symptoms appear.

• news-medical.net noted, Beyond the latest findings, other concurrent research is also advancing the understanding of bladder cancer. A May 2025 study highlighted the gut microbiome as an unexpected factor, suggesting that certain microorganisms can metabolize harmful chemicals, like those from cigarette smoke, making them more carcinogenic and increasing cancer risk.

• Further related developments include a September 2025 study published in BMJ Public Health, which proposed that a bout of cystitis, a common urinary tract infection, could serve as a new clinical marker for urological cancers.

  bcan.org reported, The research, based on data from millions of Swedish adults, found a significantly increased risk for bladder cancer in both men and women following a cystitis diagnosis, particularly within three months.

• The collaborative nature of this research, involving institutions like IRB Barcelona and the University of Washington, and its inclusion in the Cancer Grand Challenges initiative (Team PROMINENT), highlights a concerted global effort to tackle complex cancer questions.

  cancer.org noted, Such initiatives foster interdisciplinary approaches crucial for unraveling the intricate mechanisms of cancer development.

• These new insights reinforce the importance of established prevention strategies, particularly smoking cessation, which remains the leading modifiable risk factor for bladder cancer.

  news-medical.net reported, Understanding the specific cellular pathways influenced by sex and smoking could lead to more targeted prevention campaigns and personalized interventions aimed at mitigating the risk of clonal expansion in susceptible individuals.