Hormonal Regulation and Epidemiology of Esophageal Cancer

Esophageal cancer ranks among the leading causes of cancer mortality worldwide, with two main histological subtypes: adenocarcinoma and squamous cell carcinoma. A striking feature of this malignancy is its pronounced male predominance, suggesting a role for sex hormones in modulating risk and progression. Androgens and oestrogens influence epithelial homeostasis through their nuclear receptors, and imbalances in circulating hormone levels may alter the microenvironment of the oesophageal mucosa. Epidemiological patterns reveal wide geographic variation in incidence rates, linked to lifestyle factors such as obesity, gastro-oesophageal reflux and tobacco use, but also to intrinsic hormonal milieu. Population studies demonstrate that sex steroid hormones not only affect the initiation of neoplastic transformation but also shape responses to therapy and long-term survival. Mechanistic investigations have uncovered hormone-driven transcriptional programmes that enhance proliferation and invasion in cell and animal models. Taken together, these lines of evidence establish hormonal regulation as a key dimension of esophageal cancer epidemiology, with potential implications for prevention, risk stratification and the design of targeted interventions.

Research from Nature Portfolio

A comprehensive analysis of patient cohorts spanning regional and national cancer registries has confirmed the higher incidence of esophageal cancer in men across both adenocarcinoma and squamous cell subtypes. Despite this disparity, survival analyses adjusting for age, tumour stage and treatment modality found no consistent sex-specific difference in overall survival, indicating that factors beyond hormone status—such as healthcare access and comorbidities—may mediate outcomes. The study also highlighted that the male predominance in incidence has remained stable over time and is particularly marked in developed regions, underscoring the need for mechanistic studies to disentangle hormonal influences from environmental and genetic risk factors.

Hormonal Regulation and Epidemiology of Esophageal Cancer publication trend

The graph below shows the total number of articles in hormonal regulation and epidemiology of esophageal cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Androgen receptor (AR): A nuclear receptor that binds male sex steroids and regulates gene expression.

Oestrogen receptor (ER): A nuclear receptor mediating the effects of oestrogens on cell proliferation and differentiation.

Androgen-to-oestrogen ratio: The relative circulating levels of male versus female sex hormones.

5-Alpha reductase inhibitor (5ARI): A drug that prevents conversion of testosterone to the more potent dihydrotestosterone.

Adenocarcinoma: A tumour arising from glandular cells, often located in the lower oesophagus near the stomach junction.

Squamous cell carcinoma: A malignancy originating from the flat, squamous epithelial lining of the oesophagus.

Epidemiology: The study of disease distribution and determinants in populations, including incidence, prevalence and risk factors.

AP-1 transcription factor: A protein complex that controls gene expression in response to hormonal and environmental signals.

References

1. Use of 5‐alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population‐based cohort study. International Journal of Cancer (2024).
2. Androgen Receptor/AP-1 Activates UGT2B15 Transcription to Promote Esophageal Squamous Cell Carcinoma Invasion. Cancers (2023).
3. Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study. PLOS ONE (2018).
4. Sex differences in esophageal cancer overall and by histological subtype. Scientific Reports (2022).