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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?

SUBMITTER: Winder T

PROVIDER: S-EPMC3200220 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients.

Winder T T Bohanes P P Zhang W W Yang D D Power D G DG Ning Y Y Gerger A A Wilson P M PM Tang L H LH Shah M M Lee A S AS Lenz H-J HJ

Annals of oncology : official journal of the European Society for Medical Oncology 20110307 11

<h4>Background</h4>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.<h4>Patients and methods</h4>Blood samples of 234 stage ...[more]

PMID: 21382870

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Project description:IntroductionMalnutrition is a complex clinical syndrome, the exact mechanism of which is yet not fully understood. Studies have found that malnutrition is associated with anorexia and inadequate intake, tumor depletion, leptin, tumor-induced metabolic abnormalities in the body, and catabolic factors produced by the tumor in the circulation and cytokines produced by the host immune system. Among these, single nucleotide polymorphisms (SNPs) are present in the gene encoding the pro-inflammatory cytokine TNF-α.AimThe objective of this study was to investigate TNF-α -1,031 T/C gene polymorphism as an unfavorable predictor of malnutrition in patients with gastric cancer.MethodsThe study group consisted of 220 gastric cancer patients treated at Affiliated Jinhua Hospital, Zhejiang University School of Medicine. Malnutrition was mainly assessed by the Global Consensus on Malnutrition Diagnostic Criteria (GLIM). DNA was extracted from peripheral leukocytes of whole blood samples using an animal DNA extraction kit. DNA was amplified using a 1.1× T3 Super PCR mixture and genotyped using SNP1 software.ResultsThere are three major genetic polymorphisms in TNF-α. Among the 220 patients with gastric cancer, there were 7 patients with the CC genotype, 61 with the CT genotype and 152 with the TT genotype. Compared to patients with the TT genotype, patients with the C allele had an approximately 2.5-fold higher risk of developing malnutrition (p = 0.003; OR = 0.406). On the basis of multivariate analysis, patients with the CC genotype had an approximately 20.1-fold higher risk of developing malnutrition (p = 0.013; OR = 20.114), while those with the CT genotype had an almost 3.7-fold higher risk of malnutrition (p = 0.002; OR = 3.218).ConclusionSNP (-1,031 T/C) of the TNF-α may be a useful marker in the assessment of the risk of nutritional deficiencies in gastric cancer patients. Patients with gastric cancer carrying the C allele should be supported by early nutritional intervention, but more research is still needed to explore confirmation.

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GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients.

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GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients.

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