Background/aims: A family history of cancer raises the risk of gastric cancer. Microsatellite instability (MSI) is frequently observed in hereditary non-polyposis colorectal cancer (HNPCC), and gastric cancer is the most frequent extra-colonic cancer among HNPCC patients. The relationship between gastric cancer and MSI is controversial. The purpose of this study was to identify the relationship between MSI incidence and gastric cancer in patients with a family history of cancer.
Methodology: MSI incidence was examined at 5 microsatellite loci and hMLH1 and hMSH2 protein expression was examined by immunohistochemical analysis in 30 gastric cancer patients with family histories of cancer (familial group) and 37 gastric cancer patients without any family history of cancer (sporadic group).
Results: The incidence of high-frequency MSI (MSI-H) in the familial group was 33.3% (10/30) and in the sporadic group it was 5.4% (2/37) (p < 0.05). The incidence of lack of at least one mismatch repair (MMR) protein was 66.7% (8/12) in MSI-H cases, which was significantly higher than in low-frequency MSI (MSI-L) cases and microsatellite stable (MSS) cases.
Conclusions: MSI may play an important role in the development of gastric cancer in individuals with a family history of cancer and it is induced by a deficiency in MMR protein expression.