Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Sex differences in bladder cancer: emerging data and call to action

Incidence and mortality disparities between males and females exist in many diseases including bladder cancer, but the mechanisms remain unclear. To adequately address this issue, researchers must design experiments appropriately, appreciate that sex and gender are not synonymous concepts and understand that the role of both sex and gender in disease need to be elucidated.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).

    PubMed  Google Scholar 

  2. Miyamoto, H. et al. Promotion of bladder cancer development and progression by androgen receptor signals. J. Natl Cancer Inst. 99, 558–568 (2007).

    Article  CAS  Google Scholar 

  3. Chen, J. et al. Androgen dihydrotestosterone (DHT) promotes the bladder cancer nuclear AR-negative cell invasion via a newly identified membrane androgen receptor (mAR-SLC39A9)-mediated Gαi protein/MAPK/MMP9 intracellular signaling. Oncogene 39, 574–586 (2020).

    Article  CAS  Google Scholar 

  4. Deng, G. et al. Targeting androgen receptor (AR) with antiandrogen enzalutamide increases prostate cancer cell invasion yet decreases bladder cancer cell invasion via differentially altering the AR/circRNA-ARC1/miR-125b-2-3p or miR-4736/PPARγ/MMP-9 signals. Cell Death Differ. 28, 2145–2159 (2021).

    Article  CAS  Google Scholar 

  5. Sottnik, J. L. et al. Androgen receptor regulates CD44 expression in bladder cancer. Cancer Res. 81, 2833–2846 (2021).

    Article  CAS  Google Scholar 

  6. Hsu, I., Vitkus, S., Da, J. & Yeh, S. Role of oestrogen receptors in bladder cancer development. Nat. Rev. Urol. 10, 317–326 (2013).

    Article  CAS  Google Scholar 

  7. Minner, S. et al. Y chromosome loss is a frequent early event in urothelial bladder cancer. Pathology 42, 356–359 (2010).

    Article  Google Scholar 

  8. Ji, J., Zöller, B., Sundquist, J. & Sundquist, K. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: a national cohort study. Int. J. Cancer 139, 754–758 (2016).

    Article  CAS  Google Scholar 

  9. Kaneko, S. & Li, X. X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism. Sci. Adv. 4, eaar5598 (2018).

    Article  Google Scholar 

  10. Kwon, H. et al. Distinct CD8+ T cell programming in the tumor microenvironment contributes to sex bias in bladder cancer outcome. Preprint at bioRxiv https://doi.org/10.1101/2020.04.13.039735 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xue Li.

Ethics declarations

Competing interests

X.L., D.T. and Z.L. are supported by NIH grants. Z.L. sits on the scientific advisory boards for Alphamab, Henlius, Ikonisys, Heat Biologics and HanchorBio.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Theodorescu, D., Li, Z. & Li, X. Sex differences in bladder cancer: emerging data and call to action. Nat Rev Urol 19, 447–449 (2022). https://doi.org/10.1038/s41585-022-00591-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41585-022-00591-4

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing