Salt Intake Shows No Genetic Link to Gastric Cancer
SALT intake was not genetically associated with gastric cancer risk in a two-sample Mendelian randomization analysis.
The findings challenge assumptions from some observational research that high salt intake directly contributes to gastric cancer development. While dietary salt has long been considered a potential environmental risk factor, the current genetic analysis found no evidence of a causal relationship between salt intake and gastric cancer incidence.
Gastric cancer remains a major public health burden, shaped by external and internal factors. Helicobacter pylori infection is a recognized risk factor, and previous evidence has suggested that smoking, alcohol consumption, dietary patterns, and salt-rich foods may influence risk. High salt intake has been proposed to damage the gastric mucosa, promote chronic inflammation, increase DNA damage and cell proliferation, and potentially support H. pylori colonization.
However, conventional epidemiological studies have produced inconsistent results, and observational data are vulnerable to confounding and reverse causation. This study used Mendelian randomization to assess whether genetically predicted salt intake is causally associated with gastric cancer.
Mendelian Randomization Tests Gastric Cancer Risk
The analysis used summary-level genome-wide association study data for both salt intake and gastric cancer. Dietary salt intake data included up to 462,630 individuals of European ancestry and were based on responses to whether participants added salt to food, excluding salt used during cooking. Gastric cancer data included 476,116 individuals of European ancestry, including 1,029 cases and 475,087 controls.
Investigators applied inverse-variance weighted regression, MR-Egger regression, and weighted median analyses to assess the relationship between salt intake and gastric cancer. Sensitivity analyses were also used to evaluate pleiotropy and heterogeneity.
Across all primary methods, salt intake was not causally associated with gastric cancer. The inverse-variance weighted analysis reported an odds ratio of 1.1061, with a 95% confidence interval of 0.82–1.48 and a P value of .5042. MR-Egger regression and weighted median analyses also showed no statistically significant relationship.
Findings Support Cautious Interpretation
The results do not exclude the broader clinical relevance of diet, H. pylori, or other modifiable exposures in gastric cancer prevention. Instead, they suggest that genetically predicted salt intake, measured through adding salt to food, does not appear to independently drive gastric cancer risk in this dataset.
The findings may help clarify why prior observational studies have reached conflicting conclusions. For clinicians, the study reinforces the need to interpret dietary risk associations carefully, particularly when exposures are shaped by complex lifestyle, cultural, and environmental factors.
Reference
Li K et al. Causal relationships between salt intake and gastric cancer: A two-sample Mendelian randomization study. Medicine. 2026;105(18):e48510.
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