Grp78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients Journal Article
| Authors: | Winder, T.; Bohanes, P.; Zhang, W.; Yang, D.; Power, D. G.; Ning, Y.; Gerger, A.; Wilson, P. M.; Tang, L. H.; Shah, M.; Lee, A. S.; Lenz, H. J. |
| Article Title: | Grp78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients |
| Abstract: | Background: Recently, the analysis of gastric and colorectal tumor specimens determined that 78-kiloDalton glucose-regulated protein (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism protecting cells against apoptosis and can confer drug resistance. We tested whether functional polymorphisms within the GRP78 gene are related to clinical outcome in gastric and colorectal cancer (CRC) patients. Patients and methods: Blood samples of 234 stage II/III CRC patients at the University of Southern California (USC) and formalin-fixed paraffin-embedded tissues of 137 patients with localized gastric adenocarcinoma (GA) at USC and Memorial Sloan-Kettering Cancer Centers were obtained. GRP78 polymorphisms analyzed on germline DNA were correlated with clinical outcome using univariate and multivariate analyses.Results: GA patients with the combined GRP78 rs391957 C/T and T/T genotype were at higher risk for tumor recurrence and death [hazard ratio (HR) 2.61; P < 0.001 and HR 3.17; P < 0.001, respectively], than those with C/C. These findings were subsequently tested in a CRC cohort where patients with the homozygous T/T genotype were at highest risk for tumor recurrence (HR 2.61; P = 0.015). The results remained significant after adjusting for clinicopathologic determinants.Conclusion: These data provide the first evidence that the GRP78 rs391957 polymorphism can predict clinical outcome in localized GA and locally advanced CRC patients. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. |
| Keywords: | adult; controlled study; human tissue; human cell; major clinical study; overall survival; promoter region; single nucleotide polymorphism; cancer recurrence; cisplatin; fluorouracil; united states; adjuvant therapy; cancer radiotherapy; cancer staging; recurrence risk; colorectal cancer; lymphadenectomy; cohort analysis; genotype; gene frequency; prediction; cancer mortality; irinotecan; homozygosity; cancer center; dna; blood sampling; folinic acid; outcome; gastrectomy; colorectal surgery; multivariate analysis; hazard ratio; oxaliplatin; stomach adenocarcinoma; univariate analysis; formaldehyde; genetic polymorphism; paraffin; gastric cancer; polymorphism; thymine; cytosine; grp78; glucose regulated protein 78; embedding |
| Journal Title: | Annals of Oncology |
| Volume: | 22 |
| Issue: | 11 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2011-11-01 |
| Start Page: | 2431 |
| End Page: | 2439 |
| Language: | English |
| DOI: | 10.1093/annonc/mdq771 |
| PROVIDER: | scopus |
| PMCID: | PMC3200220 |
| PUBMED: | 21382870 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: ANONE" - "Source: Scopus" |
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