The association between cagA plus H-pylori infection and distal gastric cancer:: A proposed model

Cytotoxin-associated gene A (cagA)+ infection is associated with an increased risk of distal gastric cancer. The aim was to determine the effect of Helicobacter pylori (HP) on gastric mucus thickness, hydrophobicity, and PGE(2) and their relation to colonization density. Ninety-nine patients were recruited (69 HP- and 30 HP+: 10 cagA+, 18 cagA-, 2 undetermined) and six biopsies were obtained from each patient. Mucus thickness, hydrophobicity, PGE2, and colonization density were determined. HP status was assessed by histology and culture; cagA+ was determined by PCR. In age- and sex-matched patients, PGE(2) was greater in PH+ than HP- (P=0.04), with cagA+ having higher PGE(2) than HP- patients (P=0.031). No differences were observed in mucus thickness (P=0.717) or hydrophobicity (P=0.27) between HP+ and HP- patients. However, cagA+ showed a nonsignificant trend of increase in mucus thickness (P=0.784) and hydrophobicity (P=0.30) compared to cagA- and HP- patients. cagA+ colonization density was weakly correlated with increased thickness (r=0.333, P=0.381), whereas cagA- density was inversely correlated with thickness (r=-0.805, P=0.0001). A model suggesting the possible changes induced by cagA+ infection is proposed which explains the high association of cagA+ with distal gastric cancer. If supported by large multicenter studies, this could form the basis for the development of new therapies directed at the mucous layer to eradicate HP and thus reduce the risk of gastric cancer.