Sex differences in bladder cancer: understanding biological and clinical implications.

Journal: Biology of sex differences
Published Date: May 13, 2025

Abstract

Bladder cancer (BC) remains a significant global health concern, with substantial sex and racial disparities in incidence, progression, and outcomes. BC is the sixth most common cancer among males and the seventeenth most common among females worldwide. Over 90% of BC cases are urothelial carcinoma (UC) with high degrees of pathological heterogeneity. Molecular subtyping of BC has also revealed distinct luminal, basal, and neuroendocrine subtypes, each with unique genetic and immune signatures. Emerging research uncovers the biasing effects of the sex hormones with androgens increasing BC risk through both tumor cell intrinsic and extrinsic mechanisms. The sex chromosomes, including both the X and Y chromosomes, also contribute to the sex differences in BC. The effect of sex chromosome is both independent from and synergistic with the effects of sex hormones. Loss of the Y chromosome is frequently observed in BC patients, while an extra copy of the X chromosome confers better protection against BC in females than in males. Advent of advanced technologies such as multiomics and artificial intelligence will likely further improve the understanding of sex differences in BC, which may ultimately lead to personalized preventative and treatment strategies depending on the biological sex of patients. This review delves into the impacts of biology of sex on BC, emphasizing the importance of further research into sex-specific biology to improve cancer prevention and care.

Authors

  • Prakash Chaudhary
    Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Biplab Singha
    Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Hany A Abdel-Hafiz
    Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Maria Velegraki
    Pelotonia Institute for Immuno‑Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
  • Debasish Sundi
    Department of Urology, Division of Urologic Oncology, The Ohio State University, Comprehensive Cancer Center Board of Governors, Columbus, OH, USA.
  • Swati Satturwar
    Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA.
  • Anil V Parwani
    Department of Pathology, The Ohio State University Wexner Medical Centre, Columbus, OH, USA.
  • Sergei I Grivennikov
    Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Sungyong You
    Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA, USA.
  • Helen S Goodridge
    Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Qin Ma
    Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, University of Georgia, GA 30602, USA BioEnergy Science Center, TN 37831, USA.
  • Yuzhou Chang
    Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.
  • Anjun Ma
    Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • Bin Zheng
    School of Electrical and Computer Engineering, University of Oklahoma, 101 David L. Boren Blvd, Norman, OK, 73019, USA.
  • Dan Theodorescu
    Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Zihai Li
    Pelotonia Institute for Immuno‑Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
  • Xue Li
    Department of Clinical Research Center, Dazhou Central Hospital, Dazhou 635000, China.

Keywords

External Resources

Popular Topics
Recent Journals