Moter region (231G.C) is associated with the alteration of survivin

Moter region (231G.C) is associated with the alteration of IPI549 site survivin gene expression. This mutation re-upregulates the cell-cycle-dependent transcription of the human survivin gene and results in overexpression of survivin at both mRNA and protein levels [25]. Due to the complex functional mechanism and regulatory roles of survivin in tumorigenesis, the relationships between survivin 231G.C polymorphism and GIT AG120 web cancer susceptibility have been widely studied, however, these results were inconsistent. A clinical and genetic study suggested that the CC genotype of survivin 231G.C polymorphism might increase colorectal cancer risk among Caucasians [22]. Moreover, similar results have been obtained by Yang et al [25]. Their results suggested that survivin 231G.C polymorphism might be involved in distal gastric carcinogenesis and tumor differentiation among Chinese populations. Nevertheless, previous pathological study has shown that the cytoplasmic survivin expression was not a prognostic factor for advanced esophageal cancer [42]. Two recent meta-analyses by Srivastava et al and Wang et al also indicated that there was no association between survivin 231G.C polymorphism and the risk of gastric and esophageal cancers [26,27]. However, these metaanalyses did not provide convincing and reliable evidences relevant to survivin 231G.C polymorphism and GIT cancer risk because some relevant case-controlled studies were not included. Furthermore, heterogeneity was clearly evident in the results and could not be explained fully after stratified analyses based on ethnicity and cancer type. In view of these conflicting results from previous studies and the insufficient statistical power of the two recent meta-analyses, we performed the present metaanalysis to update previous meta-analyses and to provide a comprehensive and reliable conclusion by evaluating the association between survivin 231G.C polymorphism and the risk of GIT cancer. In this meta-analysis, including 2,231 GIT cancer cases and 2,287 healthy controls, the results indicated that survivin 231G.C polymorphism was associated with a significantly increased risk of GIT cancer. Although the exact function of survivin in tumorigenesis is not clear yet, a potential explanation might be that survivin gene mutations increased the ability of survivin as an inhibitor of apoptosis and regulator of cell division [43]. In the stratification analysis by cancer types, survivin 231G.C polymorphism showed significant associations with increased risk of colorectal and gastric cancers. As only two eligible studies [36,37] were identified, we did not find a a statistically significant association between survivin 231G.C polymorphism and esophageal cancer risk. These two studies were conducted in the Indian and Chinese populations from the East Asian region, respectively. However, we found an obviuos difference in the MAF of survivin 231G.C polymorphism in esophageal cancer patients from these two studies (0.40 vs 0.51). Sato et al reported that survivin was highly expressed in esophageal cancer cell lines as compared to normal organ tissues [44]. Several studies have also shown that the expression level of tumor survivin mRNA might be an important prognostic and biological marker regarding esophageal cancer patients [45?8]. Rosato et al revealed that survivin expression may be regarded as a prognostic factor only in squamous cell carcinomas but not in adenocarcinomas of the esophagus [49]. Therefore, the lack.Moter region (231G.C) is associated with the alteration of survivin gene expression. This mutation re-upregulates the cell-cycle-dependent transcription of the human survivin gene and results in overexpression of survivin at both mRNA and protein levels [25]. Due to the complex functional mechanism and regulatory roles of survivin in tumorigenesis, the relationships between survivin 231G.C polymorphism and GIT cancer susceptibility have been widely studied, however, these results were inconsistent. A clinical and genetic study suggested that the CC genotype of survivin 231G.C polymorphism might increase colorectal cancer risk among Caucasians [22]. Moreover, similar results have been obtained by Yang et al [25]. Their results suggested that survivin 231G.C polymorphism might be involved in distal gastric carcinogenesis and tumor differentiation among Chinese populations. Nevertheless, previous pathological study has shown that the cytoplasmic survivin expression was not a prognostic factor for advanced esophageal cancer [42]. Two recent meta-analyses by Srivastava et al and Wang et al also indicated that there was no association between survivin 231G.C polymorphism and the risk of gastric and esophageal cancers [26,27]. However, these metaanalyses did not provide convincing and reliable evidences relevant to survivin 231G.C polymorphism and GIT cancer risk because some relevant case-controlled studies were not included. Furthermore, heterogeneity was clearly evident in the results and could not be explained fully after stratified analyses based on ethnicity and cancer type. In view of these conflicting results from previous studies and the insufficient statistical power of the two recent meta-analyses, we performed the present metaanalysis to update previous meta-analyses and to provide a comprehensive and reliable conclusion by evaluating the association between survivin 231G.C polymorphism and the risk of GIT cancer. In this meta-analysis, including 2,231 GIT cancer cases and 2,287 healthy controls, the results indicated that survivin 231G.C polymorphism was associated with a significantly increased risk of GIT cancer. Although the exact function of survivin in tumorigenesis is not clear yet, a potential explanation might be that survivin gene mutations increased the ability of survivin as an inhibitor of apoptosis and regulator of cell division [43]. In the stratification analysis by cancer types, survivin 231G.C polymorphism showed significant associations with increased risk of colorectal and gastric cancers. As only two eligible studies [36,37] were identified, we did not find a a statistically significant association between survivin 231G.C polymorphism and esophageal cancer risk. These two studies were conducted in the Indian and Chinese populations from the East Asian region, respectively. However, we found an obviuos difference in the MAF of survivin 231G.C polymorphism in esophageal cancer patients from these two studies (0.40 vs 0.51). Sato et al reported that survivin was highly expressed in esophageal cancer cell lines as compared to normal organ tissues [44]. Several studies have also shown that the expression level of tumor survivin mRNA might be an important prognostic and biological marker regarding esophageal cancer patients [45?8]. Rosato et al revealed that survivin expression may be regarded as a prognostic factor only in squamous cell carcinomas but not in adenocarcinomas of the esophagus [49]. Therefore, the lack.