Different etiological role of Helicobacter pylori (Hp) infection in carcinogenesis between differentiated and undifferentiated gastric cancers: a nested case-control study using IgG titer against Hp surface antigen.Acta Oncol 2008; 47(3):360-5AO
The present study epidemiologically clarified the different roles of Helicobacter pylori (Hp) infection in carcinogenesis between two major histological types of noncardia gastric cancer (ncGC), intestinal (=differentiated) and diffuse (=undifferentiated), by analyzing IgG antibody titer against Hp surface antigen on the data set of a nested case-control study in a large cohort study conducted in Japan.
A total of 36,745 subjects aged 40 to 69 years in the Japan Health Center-based prospective study who responded to the baseline questionnaire and provided blood were followed over 15 years; 350 ncGC cases (differentiated=242, undifferentiated=108) matched to controls were used. Using baseline blood samples, plasma IgG titer was measured using ELISA. The level of IgG titer >10 U (cut-off value) was classified into three grades in groups of equal number: low, middle, and high.
IgG titer of Hp was significantly (p<0.01) higher in undifferentiated cases than in differentiated ones. Among the three grades of Hp IgG titer, the high titer was more closely associated with risk of undifferentiated ncGC (odds ratio (OR) for high=7.8, 95% confidence interval (CI)=2.4-24.9 vs. OR for low=6.4, 95% CI=2.1-19.6), while the low titer was a better predictor of differentiated ncGC (OR for high=3.2, 95% CI=1.6-6.4 vs. OR for low=5.9, 95% CI=3.0-11.6, trend p < 0.05). The high titer group had the lowest risk to develop differentiated ncGC with <7 years (OR=3.2, 95% CI=1.3-7.7), whereas the high titer group demonstrated the highest risk for undifferentiated ncGC developing (OR=11.6 95% CI=2.3-59.1).
Our study epidemiologically confirmed that atrophic changes caused by Hp infection determine the development of differentiated-type ncGC, and the inflammation itself induced by Hp infection promotes the development of undifferentiated-type ncGC.