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Sexual Dimorphism in Colon Cancer.
Maria Abancens1,2, Viviana Bustos3, Harry Harvey4
1Department of Molecular Medicine, RCSI University of Medicine and Health Sciences, Beaumont Hospital, Dublin, Ireland.
Frontiers in Oncology
|December 28, 2020
Summary
Colorectal cancer (CRC) shows sex differences in incidence and survival, with estrogen potentially protecting women. Estrogen influences CRC pathways, ion channels, and signaling, impacting tumor growth and patient outcomes.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Colorectal cancer (CRC) incidence is higher in males than females.
- Young women with CRC exhibit better survival than age-matched males and older women, suggesting sexual dimorphism.
- Estrogen is implicated as a protective factor in CRC development.
Purpose of the Study:
- To review clinical and molecular insights into sexual dimorphism in CRC.
- To explore the role of estrogen and the tumor microenvironment in CRC biology.
- To investigate the influence of Wnt/β-catenin signaling, ion channels, and X-linked genes.
Main Methods:
- Literature review of clinical and molecular studies on CRC sexual dimorphism.
- Analysis of estrogen's regulatory roles in CRC pathways.
- Examination of interactions between estrogen, Wnt/β-catenin, ion channels, and hypoxia-related signaling.
Main Results:
- Sexual dimorphism in CRC rates and survival is evident globally.
- Estrogen-regulated genes and signaling pathways contribute to better female survival in CRC.
- Estrogen modulates CRC proliferation via GPER, HIF1A, and VEGF signaling, particularly in hypoxic conditions.
Conclusions:
- Estrogen plays a significant protective role in colorectal cancer development and progression.
- Ion channels (KCNQ1:KCNE3) and Wnt/β-catenin signaling are key mediators of estrogen's effects in CRC.
- Understanding these sex-based differences is crucial for targeted CRC therapies.
