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.
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.
Suzuki
Gen
G
Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan. gsuzuki@niph.go.jp
Cullings
Harry
H
Fujiwara
Saeko
S
Hattori
Nobuaki
N
Matsuura
Shinsuke
S
Hakoda
Masayuki
M
Akahoshi
Masazumi
M
Kodama
Kazunori
K
Tahara
Eiichi
E
D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology*; D006790:Host-Parasite Interactions; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D009689:Nuclear Warfare; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology* / Q000469:parasitology*; D017741:Survivors
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; C080866:cagA protein, Helicobacter pylori