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Tumor Biology
Published in: Tumor Biology 6/2016

01-06-2016 | Original Article

Association of Wnt signaling pathway genetic variants in gallbladder cancer susceptibility and survival

Authors: Anu Yadav, Annapurna Gupta, Saurabh Yadav, Neeraj Rastogi, Sushma Agrawal, Ashok Kumar, Vijay Kumar, Sanjeev Misra, Balraj Mittal

Published in: Tumor Biology | Issue 6/2016

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Abstract

Gallbladder cancer (GBC) is the most common malignancy of the biliary tract with adverse prognosis and poor survival. Wnt signaling plays an important role in embryonic development and regeneration of tissues in all the species. Deregulation of expression and mutations in this pathway may lead to disease state such as cancer. In this study, we assessed the association of common germline variants of Wnt pathway genes (SFRP2, SFRP4, DKK2, DKK3, WISP3, APC, β-catenin, AXIN-2, GLI-1) to evaluate their contribution in predisposition to GBC and treatment outcomes. The study included 564 GBC patients and 250 controls. Out of 564, 200 patients were followed up for treatment response and survival. Tumor response (RECIST 1.1) was recorded in 116 patients undergoing non-adjuvant chemotherapy (NACT). Survival was assessed by Kaplan-Meier curve and Cox-proportional hazard regression. Single locus analysis showed significant association of SFRP4 rs1802073G > T [p value = 0.0001], DKK2 rs17037102C > T [p value = 0.0001], DKK3 rs3206824C > T [p value = 0.012], APC rs4595552 A/T [p value = 0.021], APC rs11954856G > T [p value = 0.047], AXIN-2 rs4791171C > T [p value = 0.001], β-catenin rs4135385A > G [p value = 0.031], and GLI-1 rs222826C > G [p value = 0.001] with increased risk of GBC. Gene-gene interaction using GMDR analysis predicted APC rs11954856 and AXIN2 rs4791171 as significant in conferring GBC susceptibility. Cox-proportional hazard model showed GLI-1 rs2228226 CG/GG and AXIN-2 rs4791171 TT genotype higher hazard ratio. In recursive partitioning, AXIN-2 rs4791171 TT genotype showed higher mortality and hazard. Most of studied genetic variants influence GBC susceptibility. APC rs11954856, GLI-1 rs2228226, and AXIN-2 rs4791171 were found to be associated with poor survival in advanced GBC patients.
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Metadata
Title
Association of Wnt signaling pathway genetic variants in gallbladder cancer susceptibility and survival
Authors
Anu Yadav
Annapurna Gupta
Saurabh Yadav
Neeraj Rastogi
Sushma Agrawal
Ashok Kumar
Vijay Kumar
Sanjeev Misra
Balraj Mittal
Publication date
01-06-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4728-9

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