Abstract
BackgroundRecent studies have implicated that members of the DICKKOPF (DKK) were causally involved in large number of human cancers. This study was designed to investigate the relationship between the genetic variations of DKK family genes and the risk of gastric cancer (GC).MethodsSix SNPs (single nucleotide polymorphisms) of DKK family genes, including rs2241529 in DKK1, rs3733635, rs17037102 and rs419764 in DKK2, rs3206824 in DKK3 and rs2073664 in DKK4, were selected and genotyped by restriction fragment length polymorphism (RFLP) and TaqMan SNP genotyping methods in 409 GC cases and 554 cancer-free controls in the Han population in eastern China.ResultsNone of the six SNPs achieved significant association with the overall GC risk and stratified analysis by age, gender, smoking status, drinking status, tumor location and pathological classification confirmed these non-significant associations.ConclusionsOur study indicated that the studied six SNPs of DKKs would not be the risk factors for GC in this Han Chinese population. Studies of larger population for different ethnicities will be needed to warrant our findings.
Highlights
Recent studies have implicated that members of the DICKKOPF (DKK) were causally involved in large number of human cancers
The mechanism of gastric carcinogenesis is complex and it is well documented that environmental elements, including Helicobacter pylori (HP) infection and life styles, such as diet pattern, alcohol consumption and tobacco smoking, may contribute to the predisposition of gastric cancer (GC) [3]
The healthy controls were selected from the visitors of the health examination clinic of Jiangsu Provincial Hospital of Traditional Chinese Medicine (TCM) who came for an annual check-up during the same study period
Summary
Recent studies have implicated that members of the DICKKOPF (DKK) were causally involved in large number of human cancers. This study was designed to investigate the relationship between the genetic variations of DKK family genes and the risk of gastric cancer (GC). Several agonists and antagonists could modulate the Wnt/β-catenin pathway and were involved in the development and progression of malignant tumors. As a member of agonists and antagonists, the Dickkopfs (DKKs) were identified as a group of secreted Wnt modulators. The cysteine rich secreted protein products of the DKKs are antagonists of Wnt glycoproteins through binding to lipoprotein receptor-related protein 5/6 (LRP5/6) and Kremen, inducing LRP endocytosis and preventing signaling to β-catenin [9]
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