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Low-Positive Antibody Titer against Helicobacter pylori Cytotoxin-Associated Gene A (CagA) May Predict Future Gastric Cancer Better Than Simple Seropositivity against H. pylori CagA or against H. pylori

Departments of ¹ Clinical Studies, ² Statistics, and ³ Epidemiology, Radiation Effects Research Foundation; ⁴ Hiroshima Cancer Seminar Foundation, Hiroshima, Japan

Requests for reprints: Gen Suzuki, Department of Environmental Health, National Institute of Public Health, 2-3-6 Minami, Wako 351-0197, Japan. Phone: 81-48-458-6254; Fax: 81-48-458-6255. E-mail: gsuzuki{at}niph.go.jp

Background: To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer.

Methods: A nested case-control study was done in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose.

Results: H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers.

Conclusions: A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1224–8)