Risk Factors for Gastric Cancer: A Large-Scale, Population-Based Case-Control Study
Gastric cancer (GC) remains a significant public health challenge in China, contributing to nearly half of global GC cases and deaths. Despite declining incidence and mortality rates over the past decade, GC ranks as the fourth most common malignancy and third leading cause of cancer-related deaths in China. Early detection is critical, as the 5-year survival rate for early-stage GC exceeds 90%, compared to 35.1% for advanced stages. This study, conducted under the National Cancer Screening Program in Urban China, aimed to identify high-risk populations for targeted screening by analyzing risk factors associated with GC.
Study Design and Methodology
The research utilized a case-control design nested within a nationwide cancer screening cohort spanning 22 provinces from 2012 to 2019. Cases were 215 individuals diagnosed with GC through endoscopic and pathological examinations. Controls (n=645) were healthy participants matched 1:3 by sex and age (±5 years). Data collection involved face-to-face interviews using a structured questionnaire covering five domains:
- Demographics: Age, sex, BMI, marital status, education level.
- Dietary habits: Consumption of fruits, vegetables, pickled foods, food temperature preferences, and salt intake.
- Lifestyle: Smoking, alcohol use, physical activity.
- Medical history: Chronic gastritis, gastric ulcers, polyps, and other stomach diseases.
- Family history: First-degree relatives with GC.
Statistical analyses included conditional logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), with significance set at P<0.05. Variables significant in univariable analysis proceeded to multivariable modeling to account for confounders.
Key Findings
Demographic and Socioeconomic Factors
Higher education levels demonstrated a protective effect. Individuals with education above primary school had a 63.8% lower GC risk compared to those with primary education or less (OR=0.362, 95% CI=0.219–0.599, P<0.001). Overweight or obesity (BMI≥24 kg/m²) reduced GC risk by 51.1% (OR=0.489, 95% CI=0.329–0.726, P<0.001).
Lifestyle Risk Factors
Smoking emerged as a major risk factor, tripling GC risk (OR=3.069, 95% CI=1.700–5.540, P<0.001). Alcohol consumption increased risk by 66% (OR=1.661, 95% CI=1.028–2.683, P=0.038). Regular physical activity showed a non-significant protective trend (OR=0.816, P=0.315).
Medical History and Familial Risks
A history of stomach disease drastically elevated GC risk. Participants with prior chronic gastritis, gastric ulcers, or polyps had 6.9 times higher odds of GC (OR=6.917, 95% CI=4.594–10.416, P<0.001). Subtypes analysis revealed:
- Chronic gastritis: OR=4.155 (95% CI=2.711–6.368).
- Gastric ulcers: OR=1.839 (95% CI=1.028–3.288).
- Gastric polyposis: OR=2.752 (95% CI=1.197–6.326).
Family history of GC in first-degree relatives quadrupled risk (OR=4.291, 95% CI=1.661–11.084, P=0.003).
Dietary Factors
High salt intake (OR=0.998, P=0.994), frequent consumption of pickled foods (OR=1.040, P=0.877), and preference for hot-temperature meals (OR=1.077, P=0.737) showed no significant associations after adjustment. Similarly, frequent fruit/vegetable intake had a non-significant protective effect (OR=0.812, P=0.359).
Subgroup Analyses
Stratified by age and sex, history of stomach disease consistently increased GC risk across all subgroups:
- Men ≤60 years: OR=5.691 (95% CI=2.327–13.917).
- Men >60 years: OR=11.031 (95% CI=5.075–23.973).
- Women ≤60 years: OR=8.622 (95% CI=3.170–23.448).
- Women >60 years: OR=5.396 (95% CI=2.141–13.603).
Discussion
Socioeconomic and Anthropometric Influences
The inverse relationship between education and GC may reflect improved health literacy, dietary habits, and access to healthcare among educated populations. The protective effect of higher BMI contrasts with some studies, potentially due to unmeasured confounders like Helicobacter pylori infection or nutritional factors not captured in this analysis.
Tobacco and Alcohol
The strong association with smoking aligns with global evidence implicating tobacco in gastric carcinogenesis, likely through DNA damage from nitrosamines and oxidative stress. Alcohol’s role, though weaker, may involve mucosal irritation and metabolic byproducts like acetaldehyde.
Chronic Gastric Pathology
Pre-existing stomach diseases, particularly chronic gastritis, highlight the importance of inflammation in GC development. Chronic gastritis often progresses to atrophic gastritis and intestinal metaplasia, recognized precancerous conditions. The elevated risk from gastric ulcers and polyps underscores the need for vigilant endoscopic monitoring in these patients.
Familial Susceptibility
The fourfold increase in GC risk among those with affected first-degree relatives suggests genetic predispositions or shared environmental exposures, such as dietary patterns or H. pylori transmission within households.
Limitations
The study’s case-control design limits causal inferences. Residual confounding (e.g., H. pylori status, detailed dietary data) and potential recall bias in self-reported histories may affect results. Additionally, the small sample size for rare exposures (e.g., remnant stomach) reduced statistical power for certain analyses.
Implications for Screening and Prevention
This study identifies smoking, alcohol use, prior stomach diseases, and family history as priority indicators for GC risk stratification. Overweight/obesity and higher education, though protective, should not preclude screening in high-risk groups. Public health strategies should emphasize:
- Targeted endoscopic screening for individuals with chronic gastritis, ulcers, or polyps.
- Smoking cessation and alcohol moderation programs.
- Familial screening for first-degree relatives of GC patients.
- Integration of BMI and socioeconomic factors into risk assessment models.
These findings provide an evidence-based framework for optimizing China’s national GC screening program, potentially reducing the burden through early detection and preventive interventions.
doi.org/10.1097/CM9.0000000000001652
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