Sex differences in bladder cancer: understanding biological and clinical implications

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 c...

Full description

Saved in:
Bibliographic Details
Main Authors: Prakash Chaudhary, Biplab Singha, Hany A. Abdel-Hafiz, Maria Velegraki, Debasish Sundi, Swati Satturwar, Anil V. Parwani, Sergei I. Grivennikov, Sungyong You, Helen S. Goodridge, Qin Ma, Yuzhou Chang, Anjun Ma, Bin Zheng, Dan Theodorescu, Zihai Li, Xue Li
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Biology of Sex Differences
Subjects:
Online Access:https://doi.org/10.1186/s13293-025-00715-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850137541967085568
author Prakash Chaudhary
Biplab Singha
Hany A. Abdel-Hafiz
Maria Velegraki
Debasish Sundi
Swati Satturwar
Anil V. Parwani
Sergei I. Grivennikov
Sungyong You
Helen S. Goodridge
Qin Ma
Yuzhou Chang
Anjun Ma
Bin Zheng
Dan Theodorescu
Zihai Li
Xue Li
author_facet Prakash Chaudhary
Biplab Singha
Hany A. Abdel-Hafiz
Maria Velegraki
Debasish Sundi
Swati Satturwar
Anil V. Parwani
Sergei I. Grivennikov
Sungyong You
Helen S. Goodridge
Qin Ma
Yuzhou Chang
Anjun Ma
Bin Zheng
Dan Theodorescu
Zihai Li
Xue Li
author_sort Prakash Chaudhary
collection DOAJ
description 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.
format Article
id doaj-art-47eed7a0ef794cf5bd9c5bacd7d9f643
institution OA Journals
issn 2042-6410
language English
publishDate 2025-05-01
publisher BMC
record_format Article
series Biology of Sex Differences
spelling doaj-art-47eed7a0ef794cf5bd9c5bacd7d9f6432025-08-20T02:30:49ZengBMCBiology of Sex Differences2042-64102025-05-0116112210.1186/s13293-025-00715-6Sex differences in bladder cancer: understanding biological and clinical implicationsPrakash Chaudhary0Biplab Singha1Hany A. Abdel-Hafiz2Maria Velegraki3Debasish Sundi4Swati Satturwar5Anil V. Parwani6Sergei I. Grivennikov7Sungyong You8Helen S. Goodridge9Qin Ma10Yuzhou Chang11Anjun Ma12Bin Zheng13Dan Theodorescu14Zihai Li15Xue Li16Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical CenterDepartment of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical CenterSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterPelotonia Institute for Immuno‑Oncology, The Ohio State University Comprehensive Cancer CenterDepartment of Urology, Division of Urologic Oncology, The Ohio State University, Comprehensive Cancer Center Board of GovernorsDepartment of Pathology, Wexner Medical Center at The Ohio State UniversityDepartment of Pathology, Wexner Medical Center at The Ohio State UniversityDepartment of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical CenterSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterDepartment of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical CenterDepartment of Biomedical Informatics, College of Medicine, The Ohio State UniversityDepartment of Biomedical Informatics, College of Medicine, The Ohio State UniversityDepartment of Biomedical Informatics, College of Medicine, The Ohio State UniversityDepartment of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical CenterSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterPelotonia Institute for Immuno‑Oncology, The Ohio State University Comprehensive Cancer CenterDepartment of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical CenterAbstract 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.https://doi.org/10.1186/s13293-025-00715-6Sex chromosomesSex hormonesNon-canonical sex-biasing factorsUrothelial carcinomaPrecision medicine
spellingShingle Prakash Chaudhary
Biplab Singha
Hany A. Abdel-Hafiz
Maria Velegraki
Debasish Sundi
Swati Satturwar
Anil V. Parwani
Sergei I. Grivennikov
Sungyong You
Helen S. Goodridge
Qin Ma
Yuzhou Chang
Anjun Ma
Bin Zheng
Dan Theodorescu
Zihai Li
Xue Li
Sex differences in bladder cancer: understanding biological and clinical implications
Biology of Sex Differences
Sex chromosomes
Sex hormones
Non-canonical sex-biasing factors
Urothelial carcinoma
Precision medicine
title Sex differences in bladder cancer: understanding biological and clinical implications
title_full Sex differences in bladder cancer: understanding biological and clinical implications
title_fullStr Sex differences in bladder cancer: understanding biological and clinical implications
title_full_unstemmed Sex differences in bladder cancer: understanding biological and clinical implications
title_short Sex differences in bladder cancer: understanding biological and clinical implications
title_sort sex differences in bladder cancer understanding biological and clinical implications
topic Sex chromosomes
Sex hormones
Non-canonical sex-biasing factors
Urothelial carcinoma
Precision medicine
url https://doi.org/10.1186/s13293-025-00715-6
work_keys_str_mv AT prakashchaudhary sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT biplabsingha sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT hanyaabdelhafiz sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT mariavelegraki sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT debasishsundi sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT swatisatturwar sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT anilvparwani sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT sergeiigrivennikov sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT sungyongyou sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT helensgoodridge sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT qinma sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT yuzhouchang sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT anjunma sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT binzheng sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT dantheodorescu sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT zihaili sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications
AT xueli sexdifferencesinbladdercancerunderstandingbiologicalandclinicalimplications