Authors: Anu Yadav Annapurna Gupta Neeraj Rastogi Sushma Agrawal Ashok Kumar Vijay Kumar Balraj Mittal
Publish Date: 2015/08/30
Volume: 37, Issue: 2, Pages: 1835-1844
Abstract
Genes important to stem cell progression have been involved in the genetics and clinical outcome of cancers We investigated germ line variants in cancer stem cell CSC genes to predict susceptibility and efficacy of chemoradiotherapy treatment in gallbladder cancer GBC patients In this study we assessed the effect of SNPs in CSC genes surface markers CD44 ALCAM EpCAM CD133 and molecular markers NANOG SOX2 LIN28A ALDH1A1 OCT4 with GBC susceptibility and prognosis Total 610 GBC patients and 250 controls were genotyped by using PCRRFLP ARMSPCR and TaqMan allelic discrimination assays Chemotoxicity graded 2–4 in 200 patients and tumor response was recorded in 140 patients undergoing neoadjuvant chemotherapy NACT Differences in genotype and haplotype frequency distributions were calculated by binary logistic regression Genegene interaction model was analyzed by generalized multifactor dimensionality reduction GMDR Overall survival was assessed by KaplanMeier survival curve and multivariate Coxproportional methods ALCAM Ars1157Crs10511244 P = 00035 haplotype was significantly associated with GBC susceptibility In GMDR analysis ALCAM rs1157GA EpCAM rs1126497TC emerged as best significant interaction model with GBC susceptibility and ALDH1A1 rs13959TG with increased risk of grade 3–4 hematological toxicity SOX2 rs11915160AC OCT4 rs3130932TG and NANOG rs11055786TC were found best genegene interaction model for predicting response to NACT In both Coxproportional and recursive partitioning ALCAM rs1157GA+AA genotype showed higher mortality and hazard ratio ALCAM gene polymorphisms associated with GBC susceptibility and survival while OCT4 SOX2 and NANOG variants showed an interactive role with treatment response
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