title: A comparison of microsatellite instability in early onset gastric carcinomas from relatively low and high incidence European populations.
abstract: We have investigated the genetic basis of gastric carcinomas 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 1 locus was detected in 44% (7 of 16) of carcinomas. A single patient demonstrated a mutator phenotype suggestive of the hereditary nonpolyposis colorectal cancer syndrome with instability in 82% of loci. This carcinoma showed loss of expression of the hMLH1 mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset gastric carcinomas from an English population, which has a relatively low incidence 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 1 marker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastritis (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 of 8) in Portuguese carcinomas compared with English cases. Genetic mechanisms underlying the hereditary non-polyposis colorectal cancer syndrome may play a role in a small number of early onset gastric carcinomas. The difference in prevalence of low-level MI between these relatively high and low incidence European populations requires further investigation.
authors.affiliation: Department of Surgery, University of Leeds, Leeds, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Hayden
authors.forename: L
authors.initials: L
authors.lastname: Cawkwell
authors.forename: M F
authors.initials: MF
authors.lastname: Dixon
authors.forename: F
authors.initials: F
authors.lastname: Pardal
authors.forename: H
authors.initials: H
authors.lastname: Murgatroyd
authors.forename: S
authors.initials: S
authors.lastname: Gray
authors.forename: P
authors.initials: P
authors.lastname: Quirke
authors.forename: I G
authors.initials: IG
authors.lastname: Martin
mesh_terms: D000328:Adult; D017668:Age of Onset; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*