A comparison of microsatellite instability in early onset gastric carcinomas from relatively low and high incidence European populations

We have investigated the genetic basis of gastric carcino mas occurring in patients aged under 40 years from a Portuguese population with a relatively high incidence of gastric cancer. We analysed a panel of 12 microsatellite loci in DNA extracted from gastric carcinomas arising in 16 patients aged 24-39 years from Braga, Portugal. Overall, microsatellite instability (MI) in at least I locus was detected in 44% (7 of 16) of carcinomas. A single p atient demonstrated a mutator phenotype suggestive of the hereditary nonpol yposis colorectal cancer syndrome with instability in 82% of loci. This car cinoma showed loss of expression of the hMLHI mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset g astric carcinomas from an English population, which has a relatively low in cidence of gastric cancer. Comparing the 2 series, we found that there was a significant difference (p = 0.04) in the prevalence of MI (at least I mar ker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastrit is (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 o f 8) in Portuguese carcinomas compared with English cases. Genetic mechanis ms underlying the hereditary non-polyposis colorectal cancer syndrome may p lay a role in a small number of early onset gastric carcinomas, The differe nce in prevalence of low-level MI between these relatively high and low inc idence European populations requires further investigation. (C) 2000 Wiley- Liss, Inc.