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Project

Gender Difference in Bladder Cancer Susceptibility

Funder: National Cancer Institute

Funding period
USD 423 K
Funding amount
Abstract
? DESCRIPTION (provided by applicant): Men are 3-4 times more likely to develop bladder cancer (BCa) than women are. In fact, the incidence of almost all types of cancer is consistently higher in males than in females. The key difference in genetic makeup between males and females is the sex chromosome complement (XX versus XY). We do not know, however, the extent to which sex chromosomes are responsible for the gender difference of BCa susceptibility. Neither do we know whether sex chromosomes enhance or reduce the gonadal hormone-dependent sexually dimorphic phenotypes. Epigenetic programming in the sexual dimorphism is an emerging field. At present, essentially nothing is known about the epigenetic mechanism of the gender difference in BCa susceptibility. Many epigenetic programs regulate histone methylation to maintain active or silent states of chromatin. The X- linked histone demethylase, Utx/Kdm6a, is an epigenetic regulator that functions in a sex-specific manner during development; this gene is mutated in over 25% of human BCa cases. Furthermore, mutation rates of epigenetic regulators are significantly higher in human BCa than all other epithelial cancers studied in The Cancer Genome Atlas (TCGA) projects. Thus, the X-linked, Utx-dependent epigenetic program may impart sex-specific gene expression differences in bladder urothelium, and consequently influence BCa susceptibility. To address questions highlighted above, we will first use a novel mouse model, which consist of the four core genotypes-XX and XY- females with ovaries, and XY-Sry and XXSry males with testes-to investigate whether the gender difference in BCa susceptibility depends on the sex chromosome complement and/or the gonadal types. Second, we will determine whether the Utx-dependent epigenetic program causes the sex disparity in BCa incidence using a mouse conditional knockout (cKO) strategy. Third, we will use genomic technology to identify sexually dimorphic genetic and epigenetic targets of the Utx-dependent epigenetic program. Identification of these molecular features may shed light onto the underlying epigenetic mechanism of the sex disparities of BCa. Together, the proposed studies will significantly improve our understanding of the gender difference in BCa susceptibility, and may substantially alter our view of the emerging paradigm of epigenetic programing in the sex disparities in cancer incidence, and could potentially lead to future epigenetic-based treatment strategies to BCa.

 
25
Projects
USD 31.0 M
Aggregated funding amount
USD 1.3 M
Average funding amount
Project list item
Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 2020
Project list item
Identifying Immunological Basis for Bladder Cancer Sex Bias

Canadian Institutes of Health Research to Hyunwoo Kwon, Zihai Li

USD 45,605
2019 - 2022
Project list item
Targeting TAM (Tyro3-Axl-Mer) family of transmembrane receptor tyrosine kinases in bladder cancer.

Bladder Cancer Advocacy Network to Arpita Roy

USD 1,700
2018 - 2018
Project list item
Novel Biomarkers for the Clinical Management of Bladder Cancer

National Cancer Institute to VINATA B LOKESHWAR

USD 902,622
2018 - 2023
Project list item
Subtyping Bladder Cancer: A Multi-omic, Exposure-informed, Genealogical Approach (MErGE)

National Cancer Institute to HEIDI ANNE HANSON

USD 298,810
2018 - 2023
Project list item
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer

United States Department of Veterans Affairs to CHONG-XIAN PAN

 
2018 - 2022
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Identify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of Smokers

National Cancer Institute to NAGIREDDY PUTLURI, RANDA A EL-ZEIN

USD 1,202,103
2018 - 2023
Project list item
New Drug and Technology Assessment in Bladder Cancer: Creation of a Novel Canadian Policy Model for Bladder Cancer

Canadian Institutes of Health Research to Girish Satish Kulkarni, Murray Dale Krahn, Shabbir Muhammad Husayn Alibhai, Peter Colin Black, Wassim Kassouf, Nathan Perlis, George Andrew Tomlinson, William Wai Lun Wong

USD 77,161
2018 - 2019
Project list item
Precision Cotargeting Tumor and Its Microenvironment in Bladder Cancer

Congressionally Directed Medical Research Programs to Hungming Lam

USD 706,000
2017 - 2018
Project list item
Delivery of Targeting Nano-Photo-Imiquimod to Enhance Response Rate of Advanced Bladder Cancer to Check Point Blockade Antibody Therapy

Congressionally Directed Medical Research Programs to Kit S Lam

USD 4,634,675
2017 - 2018
Project list item
Translation of a Clinical Molecular Diagnostic Assay for Bladder Cancer

National Cancer Institute to STEVE GOODISON

USD 1,823,874
2017 - 2022
Project list item
Racial Disparity in Bladder Cancer and Identification of Altered Metabolism in African American Compare to European Bladder Cancer

National Cancer Institute to NAGIREDDY PUTLURI

USD 1,086,461
2017 - 2022
Project list item
Development of Novel Noninvasive Tests for Prognostic Predictions for Bladder Cancer

Congressionally Directed Medical Research Programs to Vinata B Lokeshwar

USD 608,000
2016 - 2017
Project list item
Sh3gl2 and chemosensitivity of bladder cancer

National Cancer Institute to ROSALYN M ADAM

USD 492,035
2016 - 2019
Project list item
MULTIPLEXED PROTEIN BIOMARKER-BASED ASSAY FOR THE DETECTION OF BLADDER CANCER

National Cancer Institute to CHARLES J ROSSER

USD 3,471,615
2016 - 2021
Project list item
A potential role of aberrant DNA methylation in the chemoresistance in bladder cancer cells

Japan Society for the Promotion of Science to Naoya MASUMORI, 信雄 新海, Tetsuya Shindo, Naotaka NISHIYAMA

USD 41,190
2016 - 2019
Project list item
Regulation of Urinary Bladder Carcinogenesis and Progression by SPARC

National Cancer Institute to NEVEEN SAID

USD 1,726,720
2016 - 2020
Project list item
Development of a sensitive epigenomic biomarker for urothelial cancer

Japan Society for the Promotion of Science to Hiromu SUZUKI, Naoya MASUMORI

USD 32,060
2015 - 2017
Project list item
Development of molecular assays for non-invasive bladder cancer detection

National Cancer Institute to STEVE GOODISON

USD 2,005,344
2013 - 2017
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