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
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
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).
Miyamoto, H. et al. Promotion of bladder cancer development and progression by androgen receptor signals. J. Natl Cancer Inst. 99, 558–568 (2007).
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).
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).
Sottnik, J. L. et al. Androgen receptor regulates CD44 expression in bladder cancer. Cancer Res. 81, 2833–2846 (2021).
Hsu, I., Vitkus, S., Da, J. & Yeh, S. Role of oestrogen receptors in bladder cancer development. Nat. Rev. Urol. 10, 317–326 (2013).
Minner, S. et al. Y chromosome loss is a frequent early event in urothelial bladder cancer. Pathology 42, 356–359 (2010).
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).
Kaneko, S. & Li, X. X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism. Sci. Adv. 4, eaar5598 (2018).
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).
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.
About this article
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