BAX and CDKN1A polymorphisms correlated with clinical outcomes of gastric cancer patients treated with postoperative chemotherapy

Med Oncol. 2014 Nov;31(11):249. doi: 10.1007/s12032-014-0249-4. Epub 2014 Sep 30.

Abstract

This study aims to examine the correlation between two single nucleotide polymorphisms (SNPs) of apoptosis-related genes and clinical outcomes in gastric cancer. A total of 221 patients with stage T2 and T3 gastric cancer treated with postoperative chemotherapy between 2003 and 2008 were retrospectively collected in this study to explore the association of rs4645878 located in BAX gene and rs1801270 located in CDKN1A gene with survival, recurrence, and toxicity to chemotherapy. Additionally, immunohistochemistry was used to detect the BAX expression in gastric cancer tissues. Patients carrying at least one variant genotype in BAX SNP (rs4645878) showed a significantly increased recurrence risk [hazard ratio (HR) 2.63; 95 % confidence internal (95 % CI) 1.71-4.03] and poor survival (HR 2.89; 95 % CI 1.88-4.44). Moreover, the recurrence and survival rate in patients with GA genotype was 72.7 and 24.7 %, respectively, compared with total recurrence rate of 54.8 %, P = 0.006, and compared with total survival rate of 46.6 %, P = 0.001. In addition, the GA genotype was related to lower BAX expression in gastric cancer tissues. The CDKN1A (rs1801270) mutant genotype was associated with a significantly decreased risk of hematologic toxicity [odds ratio (OR) 0.28; 95 % CI 0.12-0.63]. SNPs located in BAX and CDKN1A genes are closely associated with clinical outcomes in patients with gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Postoperative Care / mortality
  • Postoperative Care / trends
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Survival Rate / trends
  • Treatment Outcome
  • Young Adult
  • bcl-2-Associated X Protein / genetics*

Substances

  • BAX protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • bcl-2-Associated X Protein