Details

Autor(en) / Beteiligte

• Winder, T
• Wilson, P M
• Yang, D
• Zhang, W
• Ning, Y
• Power, D G
• Bohanes, P
• Gerger, A
• Tang, L H
• Shah, M
• Lenz, H-J

Titel

An individual coding polymorphism and the haplotype of the SPARC gene predict gastric cancer recurrence

Ist Teil von

• The pharmacogenomics journal, 2013-08, Vol.13 (4), p.342-348

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• The 5-year survival rate for gastric adenocarcinoma (GA) remains only 40% and biomarkers to identify patients at high risk of tumor recurrence are urgently needed. Secreted protein acidic and rich in cysteine ( SPARC ) is an extracellular matrix glycoprotein that mediates cell matrix interactions, and upregulation of SPARC can promote tumor progression and metastasis. This study investigated whether single-nucleotide polymorphisms (SNPs) in SPARC impact the prognosis of GA. Blood or formalin-fixed, paraffin-embedded tissues were obtained from 137 GA patients at the University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was isolated and five SNPs in the SPARC 3′-untranslated region (UTR) were evaluated by DNA sequencing or PCR-restriction fragment length polymorphism. Associations between SNPs and time to tumor recurrence (TTR) were analyzed using Kaplan–Meier curves, log-rank tests, and likelihood-ratio test within logistic or Cox regression model as appropriate. Patients carrying at least one G allele of the SPARC rs1059829 polymorphism (GG, AG) showed a median TTR of 3.7 years compared with 2.1 years TTR for patients with AA (hazard ratio (HR) 0.57; P =0.033). In a multivariate analysis adjusted for T and N category as covariates and stratified by race, hospital and chemotherapy, patients with at least one SPARC rs1059829 G allele (GG, AG) remained significantly associated with superior TTR than patients with AA genotype (adjusted P =0.026). In addition, patients harboring the G-A-A haplotype had the highest risk of tumor recurrence (HR 1.892; adjusted P =0.016). Our findings suggest that SPARC 3′-UTR SNPs may be useful in predicting GA patients at increased risk of recurrence.