A case-control study on atrophic gastritis and gastric cancer using stored sera and genome DNA.

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Background ＆ Aims : To investigate, firstly, the relationship between radiation dose and gastric cancer after full adjustment of various risk factors, and secondly to investigate the Gig antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer. Methods : A nested case-control study was performed in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean=2.3years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, time and type of serum storage, and counter-matched on radiation dose. As to 172 cases and 1071 controls, we also used stored sera 8.6 years before diagnosis. 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%C.I. 2.1-7.0, p<0.001), especially for intestinal type tumor (RR=9.9, 95%C.I. 3.5,27.4, p<0.001), compared with other risk factors, H.pylori IgG-seropositive with CagA Gig negative (RR=2.2, 95%C.I. 1.3-3.9, p=0.0052), H.pylori IgG-seropositive with CagA IgG_high titer (RR=2.0,95%C.I. 1.3-3.2, p=0.0022), chronic atrophic gastritis (RR=2.4,95%C.I. 1.8-3.3, p<0.001), current smoking (RR=2.3,95%C.I 1.4-3.5, p<0.001) or radiation dose (RR=2.1,95%C.I. 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 non-smokers, all noncardia and diffuse type gastric cancers. Low antibody titer to CagA was not due to the rapid progression of atrophic gastritis, because the progression rate did not differ between low titer and high titer groups. 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.