The pathways of gastric cancer in young patients (40 years of age or younger) have not yet been determined. We therefore examined clinicopathologically and genetically 68 gastric cancers in young patients and 66 tumors in older patients (41 years of age or older). Mutations in B-raf and K-ras were identified by PCR-SSCP following sequencing. Microsatellite instability (MSI) and hMLH3 mutations were also examined. Histopathologically, diffuse-type gastric cancer and cancer in the whole of the stomach were found significantly more often in young patients than in older patients (21% vs. 2%, P=0.0006, and 77% vs. 32%, P<0.0001, respectively). Genetically, MSI and hMLH3 mutations were found significantly more often in tumors in young patients than in tumors in older patients (15% vs. 4%, P=0.040, and 9% vs. 0%, P=0.036, respectively). Tumors in young female patients were found significantly less often in the lower-third of the stomach and showed a significantly greater frequency of MSI, compared to tumors in young male patients (33% vs. 9%, P=0.046, 5% vs. 30%, P=0.010, respectively). These results suggest that the pathways of gastric carcinogenesis differ between young patients and older patients, and that the pathways differ between the sexes in young patients.

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