AIM: To examine the interactions between cytotoxinassociated gene (CagA) positive Helicobacter pylori infection and smoking in non-cardiac gastric cancer.METHODS: 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 enzymelinked immunosorbent assays.RESULTS: 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 highexposure 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).CONCLUSION: These findings support a meaningful interaction between CagA and smoking for the risk of gastric cancer which may have implications for its early detection. AIM: To examine the interactions between cytotoxinassociated gene (CagA) positive Helicobacter pylori infection and smoking in non-cardiac gastric cancer. METHODS: 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 as surveys 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 enzymelinked immunosorbent assays .RESULTS: Smoking and CagA infection were statistically significant risk factors of non-cardiac cancer. CagA was categorized in tertiles, an d 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 highexposure category was compared with the low-exposure category.Smokers had an OR of 5.4 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: 2.3-9.0, P = 0.002) : 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. Adjustment after 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). CONCLUSION: These findings support a meaningful interaction between CagA and smoking for the risk of gastric cancer which may have implications for its early detecti on.