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Accumulated evidence indicates that the incidence of early-onset breast cancer has rapidly increased in Taiwan and other Asian compared to Western countries. The mismatch repair (MMR) pathway might be one of the crucial mechanisms of predisposition to early breast cancer. In this study, we explored whether MMR gene polymorphisms contribute to the risk of breast cancer in young women. This was a 2-stage case–control study including 737 cases and 719 controls. After eight single nucleotide polymorphisms (SNPs) were genotyped in MMR pathway genes in the stage I study, a promising SNP, MSH2 rs2303425, was selected for validation in the stage II study. A luciferase reporter assay was used to evaluate the transcriptional activity of MSH2. Logistic regression analysis showed that individuals with the MSH2 rs2303425 C/C genotype had a significantly increased risk of breast cancer compared to those with the T/T genotype (adjusted odds ratio 2.0; 95 % confidence interval 1.1–3.8), particularly in early-onset breast cancer patients with the luminal A subtype. The luciferase assay in three cell lines indicated that the MSH2 rs2303425 T/C substitution decreased MSH2 expression, which is consistent with the finding of an association study. A common variant SNP in MSH2 may contribute to the susceptibility to early-onset breast cancer functionally, particularly for the luminal A subtype.

The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rapidly increasing. We evaluated the clinicopathological difference and outcomes of Taiwanese patients with AEG according to the Siewert classification.Data were prospectively collected between December 1987 and July 2007. Two hundred thirty-one patients underwent curative resection of AEG at Taipei Veterans General Hospital and were divided into different Siewert types. The clinicopathological characteristics, operative morbidity, survival, and initial recurrence pattern were compared between the different types.Fifty-one type II and 180 type III cancer patients were studied. Subtotal esophagectomy via a left thoracotomy (19.6% vs 2.8%), smaller tumor size (4.43 +/- 2.04 vs. 5.35 +/- 2.03 cm), and more combined organ resection (60% vs. 43.1%) were more common in type II than type III cancer. Multivariate analysis showed that three independent risk factors for death were gender, tumor size, and lymphovascular invasion. There were long-term survivors among the patients with lesser curvature site lymph node metastasis, whereas metastasis to the lymph nodes of the distal stomach and along the greater curvature site was associated with poor prognosis. The 5-year survival was similar between type II and type III cancer (59.6% vs. 63.5%, P = 0.947).Lymphovascular invasion, tumor size, and gender were determined to be three independent factors of survival after curative resection for AEG, and Siewert type was not associated with differences in survival.