title: An individual coding polymorphism and the haplotype of the SPARC gene predict gastric cancer recurrence.
abstract: 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.
authors.affiliation: Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Winder
authors.forename: P M
authors.initials: PM
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.forename: D G
authors.initials: DG
authors.lastname: Power
authors.forename: P
authors.initials: P
authors.lastname: Bohanes
authors.forename: A
authors.initials: A
authors.lastname: Gerger
authors.forename: L H
authors.initials: LH
authors.lastname: Tang
authors.forename: M
authors.initials: M
authors.lastname: Shah
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D015676:Osteonectin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D015676:Osteonectin; C577241:SPARC protein, human