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.

New Angiogenic Regulators Produced by TAMs: Perspective for Targeting Tumor Angiogenesis

“…Without the genetic influence of SPP1, polymorph variants of SPARC (rs1054204, rs3210714, and rs3549) had no effect on gastric cancer risk [192]. An individual SPARC polymorphism c.*1103G > A (rs1059829), allele G, significantly correlated with tumor recurrence in gastric cancer [193]. SPARC polymorphisms c.*1200G > A (rs3210714) and c.331-59 A > C (rs7719521), genotypes AG + GG and AC + CC, respectively, were significantly associated with higher VEGF protein expression in breast cancer tissue compare to AA genotypes, which may explain the correlation with higher breast cancer risk and worse prognosis [194].…”

Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk

“…Gastric cancer is one of the major contributors to cancer-related deaths worldwide with estimated 989 600 new cases and 738 000 deaths in 2008. 1 , 2 It is believed that complex interplay of genetic and environmental factors triggers the accumulation of numerous genetic and epigenetic alterations in cells, resulting in deregulation of normal cell functions and disruption of stomach linen homeostasis. 3 - 6 Individual genetic factors probably contribute to aberrant processes in the genesis of malignant phenotype.…”

Secreted Protein Acidic and Rich in Cysteine (SPARC) Polymorphisms in Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer Patients

“…It also participates in the immune response and in malignant transformation processes [40][41][42][43]. Variants in the SPARC gene have been identified as susceptibility factors [44,45] and as predictor and prognostic biomarkers in some cancers [31,46]. SPARC variants as biomarkers for breast cancer risk and prognosis have only been previously proposed in a case-control study [47].…”