Blood Type A is Associated with Increased Gastric Cancer Risk
Yes, blood type A is associated with an approximately 20% increased risk of gastric cancer compared to other blood types, while blood type O appears protective. This association has been consistently demonstrated across multiple large-scale studies and represents a non-modifiable genetic risk factor that should be considered alongside other established risk factors when assessing gastric cancer risk 1, 2, 3.
Magnitude of Risk
The increased risk associated with blood type A is modest but clinically meaningful:
- Blood type A individuals have a 1.20-fold increased risk (95% CI: 1.02-1.42) of gastric cancer compared to other blood types 1
- Blood type AB also shows elevated risk with an odds ratio of 1.18 (95% CI: 1.02-1.36) in Chinese populations and 1.09 (95% CI: 1.03-1.16) in meta-analysis 2
- Blood type O appears protective with a reduced risk (OR = 0.80; 95% CI: 0.72-0.88) compared to non-O blood groups 3
These findings have been validated in a large meta-analysis of 40 studies including 33,613 cases and 2,431,327 controls, confirming blood group A (OR = 1.19,95% CI: 1.13-1.25) and AB (OR = 1.09,95% CI: 1.03-1.16) associations with increased gastric cancer risk 2.
Interaction with H. pylori Infection
The blood type association is significantly modified by H. pylori cagA status, creating distinct risk profiles:
- Blood type A individuals infected with cagA-positive H. pylori strains have a 1.42-fold increased risk (95% CI: 1.09-1.86) of intestinal metaplasia or dysplasia compared to blood type O individuals with the same infection 4
- The combined risk of blood type A plus cagA-positive H. pylori infection yields an OR of 3.82 (95% CI: 2.80-5.20) compared to non-A blood groups with cagA-negative strains 4
- Blood type A individuals are more susceptible to H. pylori infection itself (OR = 1.42; 95% CI: 1.05-1.93) 3
- Paradoxically, among those with cagA-negative H. pylori or no infection, blood type A shows a protective effect (OR = 0.60; 95% CI: 0.38-0.94) 4
Clinical Integration with Other Risk Factors
Blood type should be considered within the comprehensive risk assessment framework outlined in current gastric cancer screening guidelines 5:
Primary Risk Factors to Assess Alongside Blood Type:
- H. pylori infection status and cagA positivity - the most modifiable and important risk factor 6
- Family history - first-degree relative with gastric cancer increases risk 2-3 fold, and when combined with blood type A, yields an OR of 2.61 (95% CI: 1.59-4.30) for dysplasia 7, 6
- Geographic origin - first-generation immigrants from high-incidence regions (East Asia, Andean Latin America, Eastern Europe) 5, 6
- Age - peak incidence in seventh decade 6
- Male gender - approximately 2-fold increased risk 6
- Tobacco exposure 5, 6
- Persistent poverty - 43% higher mortality rates 6
- Hereditary cancer syndromes (Lynch syndrome, familial adenomatous polyposis, etc.) 5
Practical Clinical Application
Blood type A should lower the threshold for gastric cancer screening when combined with other risk factors, though it is not sufficient alone to warrant screening 5, 8:
When to Consider Screening:
- Blood type A PLUS first-degree relative with gastric cancer - particularly strong indication given combined OR of 2.61 for precancerous lesions 7
- Blood type A PLUS cagA-positive H. pylori infection - highest risk group requiring H. pylori eradication and consideration for surveillance 4
- Blood type A PLUS immigration from high-incidence region - especially first-generation immigrants 5, 6
- Blood type A PLUS multiple modifiable risk factors (smoking, high salt diet, persistent poverty) 5, 6
Important Caveats:
Blood type is a non-modifiable risk factor - clinical efforts should prioritize modifiable factors including H. pylori eradication, smoking cessation, and dietary modification 8, 6
The absolute risk increase is modest - blood type A increases relative risk by approximately 20%, but the baseline risk in the general U.S. population remains low outside of high-risk groups 1, 2
Current U.S. guidelines do not include blood type in formal risk stratification algorithms, focusing instead on ethnicity, family history, H. pylori status, and hereditary syndromes 5
Mechanism and Precancerous Lesions
Blood type A is associated with increased risk of precancerous gastric lesions, not just invasive cancer:
- Dysplasia risk - OR = 1.39 (95% CI: 1.12-1.73) for blood type A 7
- Intestinal metaplasia risk - OR = 1.28 (95% CI: 1.06-1.53) for blood type A 7
This suggests blood type influences early stages of the gastric carcinogenesis cascade, particularly in the context of H. pylori-induced inflammation and progression through atrophic gastritis to intestinal metaplasia and dysplasia 4, 7.