Department of Medical Oncology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
Department of Physiology, Michigan State University, East Lansing 48824, USA.
Cancer Biol Med. 2024 Oct 30;21(10):898-915. doi: 10.20892/j.issn.2095-3941.2024.0224.
Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.
性别差异在不同类型的消化系统癌症中显而易见，女性的发病率和死亡率通常低于男性。这一发现表明女性甾体激素（尤其是雌激素）在这些癌症的发展中可能具有保护作用。雌激素是一种众所周知的性激素，不仅调节生殖系统，还通过与雌激素受体（ERs）的相互作用对非生殖器官发挥多种作用，包括经典（ERα和 ERβ）和非传统 ERs [G 蛋白偶联雌激素受体（GPER）]。最近的进展有助于我们理解 ERs 在消化系统癌症中的作用机制。在这篇综合综述中，我们总结了目前对雌激素和 ERs 在主要类型的消化系统癌症（包括肝细胞癌、胰腺癌、食管癌、胃癌和结直肠癌）中所起的复杂作用的理解。此外，我们还讨论了 ERα、ERβ 和 GPER 作用的潜在分子机制，并提出了针对雌激素和 ERs 调节途径的创新治疗和预防措施的观点。雌激素和 ERs 在消化系统癌症中的作用是复杂的，取决于所涉及的细胞类型和组织。此外，解析雌激素、ERs 及其相关信号通路的复杂作用可能会指导针对消化系统癌症的新型、个体化治疗和预防策略的发现，最终改善全球大量受这些恶性肿瘤影响的个体的护理和临床结局。
