Familial Risk Factors in Gastric Cancer
Summary
Gastric cancer exhibits a substantial familial component, with individuals who have an affected first-degree relative facing a roughly 1.5–2-fold increased risk. Both inherited and shared environmental factors contribute to this clustering. Rare high-penetrance syndromes, most notably hereditary diffuse gastric cancer caused by germline mutations in the CDH1 gene, account for a small proportion of cases but illustrate the impact of single-gene defects. More commonly, a polygenic background of low-penetrance variants interacts with host factors such as chronic Helicobacter pylori infection, dietary habits and socioeconomic determinants to modulate risk. Anatomical and histological subtypes differ in their familial associations: non-cardia and diffuse-type cancers often show stronger familial aggregation than cardia or intestinal-type tumours. Early-onset disease and multiple affected relatives further elevate risk and justify enhanced surveillance strategies, including endoscopic screening and genetic counselling. Advances in molecular profiling and risk stratification promise personalised prevention, while global cohort studies emphasise the need to adapt guidelines to diverse populations and resource settings.
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Familial Risk Factors in Gastric Cancer publication trend
The graph below shows the total number of articles in familial risk factors in gastric cancer across all publications each year (not limited to Nature Index journals).
Technical terms
Germline mutation: inherited alteration in a gene present in all cells, capable of predisposing to cancer.
First-degree relative: parent, sibling or child sharing approximately 50% of one’s genetic material.
Histological subtype: classification of cancer based on microscopic tissue architecture, such as diffuse or intestinal types in gastric cancer.
Hazard ratio (HR): measure comparing the rate of an event (e.g. cancer incidence or death) between two groups over time.
Atrophic gastritis: chronic inflammation and loss of gastric glandular cells that can precede intestinal metaplasia and cancer.
References
- Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants. Gastric Cancer (2024).
- Family history and the risk of gastric cancer. British Journal of Cancer (2009).
- Healthy Lifestyle Factors, Cancer Family History, and Gastric Cancer Risk: A Population-Based Case-Control Study in China. Frontiers in Nutrition (2021).
- Family History and Risk of Upper Gastrointestinal Cancer in the Linxian General Population. Frontiers in Oncology (2021).
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