ression Predict Poor Breast Cancer Survival

ownloade kground: Matriptase plays a role in carcinogenesis, but the role of its genetic variation or that of the cyte growth factor activator inhibitor-1 (HAI-1) has not been evaluated. This study aimed to examine netic variation of matriptase (ST14 gene) and HAI-1 (SPINT1 gene) in breast cancer risk and prognosis, ess matriptase and HAI-1 gene and protein expression in breast tumors, and to identify their clinicoogic correlations and prognostic significance. thods: Five single nucleotide polymorphisms in ST14 and three in SPINT1 were genotyped in 470 inbreast cancer cases and 446 healthy controls. Gene expression analysis was done for 40 breast cancer es. Protein expression was assessed by immunohistochemical analyses in 377 invasive breast tumors. atistical significance of the associations among genotypes, clinicopathologic variables, and prognosis ssessed. ults: The ST14 single nucleotide polymorphism rs704624 independently predicted breast cancer survivoor outcome associated with the minor allele (P = 0.001; risk ratio, 2.221; 95% confidence interval, 1.382. Moreover, ST14 gene expression levels were lower among the minor allele carriers (P = 0.009), and ve/low matriptase protein expression was independently predictive of poorer survival (P = 0.046; risk 1.554; 95% confidence interval, 1.008-2.396). clusions: The ST14 variant rs704624 and protein expression of matriptase have prognostic significance st cancer. This study adds to the evidence for the role of matriptase in breast cancer and has found new ce for the genotypes having an impact in breast cancer. act: This is the first study showing that genetic variation in matriptase has clinical importance. The Imp results encourage further study on the genetic variation affecting protein levels and function in type II transmembrane serine proteases. Cancer Epidemiol Biomarkers Prev; 19(9); 2133–42. ©2010 AACR.