O6-methylguanine in blood leucocyte DNA: an association with the geographic prevalence of gastric cancer and with low levels of serum pepsinogen A, a marker of severe chronic atrophic gastritis. The EUROGAST Study Group.

Using a competitive repair assay, 407 samples of peripheral blood leucocyte DNA from randomly selected subjects in 17 populations were tested for the presence of the adduct O6-methylguanine. With a limit of assay sensitivity of 0.05 fmol/micrograms DNA, the adduct was detected in 21 samples (5%). Sixteen positive samples came from 102 tested (16%) from two populations, in Japan and Portugal, with extremely high gastric cancer rates. This was significantly higher (P < 0.001) than the three positive samples out of 216 tested (1%) from populations with low or intermediate rates of gastric cancer. There was also an association between presence of the adduct and having a low (< 25 ng/ml) level of serum pepsinogen A, a marker of severe chronic atrophic gastritis. These results are consistent with the general involvement of methylating agents in the pathogenesis of gastric cancer and with the model proposing formation of such compounds by endogenous nitrosation in the hypochlorhydric stomach.