Hormonal Influences on Gastric Cancer Epidemiology
Summary
Gastric cancer displays marked variation in incidence and outcomes between sexes and across populations, implicating hormonal factors in both risk and progression. Endogenous hormones such as oestrogens and androgens appear to modulate gastric mucosal biology, while obesity-related peptides influence inflammatory and proliferative pathways. Men typically exhibit higher incidence rates, whereas women of reproductive age show a relative protection that wanes after menopause. Exogenous hormone exposures—whether contraceptive agents or hormone replacement therapy—have been linked to altered risk profiles. Emerging evidence also highlights the role of metabolic hormones, including insulin-like growth factor-1, leptin and ghrelin, in promoting or inhibiting tumour development at distinct gastric subsites. Together, these findings underscore a complex interplay between systemic endocrine cues and local gastric microenvironments, with implications for personalised prevention and therapeutic strategies.
Research from Nature Portfolio
A comprehensive meta-analysis evaluated the association between menopausal hormone therapy and gastric cancer risk in nearly two million women. It demonstrated that use of oestrogen-only and combined oestrogen–progestin regimens was consistently linked to a 28–37% reduction in gastric cancer incidence, regardless of formulation. The evidence displayed minimal heterogeneity, suggesting a robust inverse association. Mechanistic hypotheses centre on oestrogen’s capacity to modulate gastric epithelial proliferation, reduce chronic inflammation and influence cytokine networks. These insights support a protective role for exogenous oestrogens in gastric carcinogenesis, highlighting potential for endocrine-based risk reduction approaches in postmenopausal populations.
Hormonal Influences on Gastric Cancer Epidemiology publication trend
The graph below shows the total number of articles in hormonal influences on gastric cancer epidemiology across all publications each year (not limited to Nature Index journals).
Technical terms
Epidemiology: Study of the distribution and determinants of health-related events in populations.
Insulin-like growth factor-1 (IGF-1): A peptide hormone promoting cell proliferation and survival, implicated in tumour development.
Leptin: An adipocyte-derived hormone that regulates energy balance and may influence inflammatory and growth pathways in cancer.
Ghrelin: A stomach-secreted peptide that stimulates appetite and may exert protective effects against gastric malignancy.
Oestrogen receptor (ER): A nuclear transcription factor activated by oestrogen, modulating gene expression involved in cell proliferation and survival.
Hormone replacement therapy (HRT): Administration of exogenous oestrogen, alone or with progestin, to alleviate menopausal symptoms and potentially alter cancer risk.
References
- Circulating hormones and risk of gastric cancer by subsite in three cohort studies. Gastric Cancer (2023).
- Female Sex but Not Oestrogen Receptor Expression Predicts Survival in Advanced Gastroesophageal Adenocarcinoma—A Post-hoc Analysis of the GO2 Trial. Cancers (2023).
- Association of hormone replacement therapy with risk of gastric cancer: a systematic review and meta-analysis. Scientific Reports (2022).
- Menstrual and Reproductive Factors and Risk of Gastric and Colorectal Cancer in Spain. PLOS ONE (2016).
- Sex Disparity in Patients with Gastric Cancer: A Systematic Review and Meta‐Analysis. Journal of Oncology (2022).
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