Interactions between CagA and smoking in gastric cancer

To examine the interactions between cytotoxin-associated gene (CagA) positive Helicobacter pylori infection and smoking in non-cardiac gastric cancer.

A case-control study (257 cases and 514 frequency-matched controls) was conducted from September 2008 to July 2010 in Xi'an, China. Cases were newly diagnosed, histologically confirmed non-cardiac cancer. Controls were randomly selected from similar communities to the cases and were further matched by sex and age (± 5 years). A face-to-face interview was performed by the investigators for each participant. Data were obtained using a standardized questionnaire that included questions regarding known or suspected lifestyle and environmental risk factors of gastric cancer. A 5 mL sample of fasting venous blood was taken. CagA infection was serologically detected by enzyme-linked immunosorbent assays.

Smoking and CagA infection were statistically significant risk factors of non-cardiac cancer. CagA was categorized in tertiles, and the odds ratio (OR) was 12.4 (95% CI: 6.1-20.3, P = 0.003) for CagA after being adjusted for confounding factors when the high-exposure category was compared with the low-exposure category. Smokers had an OR of 5.4 compared with subjects who never smoked (95% CI: 2.3-9.0, P = 0.002). The OR of non-cardiac cancer was 3.5 (95% CI: 1.8-5.3) for non-smokers with CagA infection, 3.5 (95% CI: 1.9-5.1) for smokers without CagA infection, and 8.7 (95% CI: 5.1-11.9) for smokers with CagA infection compared with subjects without these risk factors. After adjusting for confounding factors, the corresponding ORs of non-cardiac cancer were 3.2 (95% CI: 1.5-6.8), 2.7 (95% CI: 1.3-4.9) and 19.5 (95% CI: 10.3-42.2), respectively. There was a multiplicative interaction between smoking and CagA, with a synergistic factor of 2.257 (Z = 2.315, P = 0.021).

These findings support a meaningful interaction between CagA and smoking for the risk of gastric cancer which may have implications for its early detection.