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Red Meat, Family History, and Increased Risk of Gastric Cancer with Microsatellite Instability¹

Epidemiology Unit, Centro per lo Studio e la Prevenzione Oncologica, 50135 Florence, Italy [D. P., A. R., G. M., C. S.]; Department of Oncology and Neurosciences, University "Gabriele D’Annunzio," Chieti, Italy [L. O., A. C., C. D., M. F., R. P., R. M. C.]; Department of Experimental Medicine and Pathology, University "La Sapienza," Rome, Italy [L. O., C. D., M. F.]; Department of Pathology, Florence University, Florence, Italy [A. A.]; Sezione di Statistica Medica e Biometria, Università degli Studi, Brescia, Italy [A. D.]; and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852 [J. F. F.]

Microsatellite instability (MSI) occurs frequently in sporadic gastric cancer (GC) and may define a distinctive molecular pathway of carcinogenesis. We evaluated the role of dietary risk factors in GC according to MSI status. A large series of 382 GC cases and 561 controls were originally identified in a population-based case-control study carried out in the high-risk area around Florence, Italy; 126 GC patients were typed for MSI status. A MSI+ phenotype was detected in 43 of 126 cases (34.1%), whereas 83 cases were classified as MSI-. A multinomial logistic regression model was used to compare the two subgroups of GC classified according to MSI status in the same analysis, with all of the available population controls. A case-case approach was also used. The risk of MSI+ tumors was positively associated with high consumption of red meat and meat sauce and negatively associated with consumption of white meat. A positive association was also seen with total protein and nitrite intake, whereas no relation was found with micronutrient intake. Risk was especially high among subjects reporting both a positive GC family history and a high consumption of red meat (odds ratio, 25.7; 95% confidence interval, 6.4–102.8). For MSI- tumors, a significant protective effect was associated with frequent consumption of citrus and other fresh fruit, garlic, legumes, vegetables, and olive oil and with high intake of ß-carotene and other antioxidants and sugar, whereas positive associations were seen with protein and sodium intake. In summary, a specific dietary pattern emerged for MSI+ gastric tumors, suggesting that factors related to red meat consumption are involved in this pathway, particularly among individuals with a positive family history. In contrast, the risk of MSI- tumors was strongly reduced by the frequent consumption of fresh fruit and vegetables.

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