FREQUENT COOCCURRENCE OF MUTATOR PHENOTYPE IN SYNCHRONOUS, INDEPENDENT MULTIPLE CANCERS OF THE STOMACH

The prevalence of multiple independent primary cancer of the stomach i s high in Japanese, We hypothesized that individuals with multiple, in dependent gastric cancers might have a greater genetic susceptibility than persons with solitary gastric cancer at the time of diagnosis, We therefore determined the frequency of mutator phenotypes in 20 person s with independent multiple gastric cancers and 42 persons with solita ry primary lesions, The mutator phenotype was determined by examining dinucleotide CA repeats at the microsatellite loci D2S136 (chromosome 2), MSX2 (chromosome 5q34), D5S82 (chromosome 5q14-q21) and TP53 (chro mosome 17p13,1), Although there were no significant differences betwee n the clinical and pathological features (stage or histopathological s ubtype) of the two groups, the prevalence of any one microsatellite in stability in patients with multiple gastric cancer was greater (65% ve rsus 24%; P = 0.003) than in those with solitary gastric cancer, The p revalence of co-occurrence of mutator phenotype in synchronous lesions was greater than expected based on their frequency in solitary gastri c cancer (12% versus 9%x9%), Persons with advanced-stage multiple prim ary lesions were more likely to exhibit the mutator phenotype (P = 0.1 0), These findings indicate that individual predisposition for qualita tive or quantitative defects in DNA repair systems significantly contr ibute to the simultaneous occurrence of gastric cancer in Japanese.