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

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.

Prognostic value and susceptibility of BAX rs4645878 polymorphism in cancer

“…Owing to genetic distribution of controls deviating from HWE and insufficient data, 7 articles were excluded. In the end, after serious of filters were applied, 14 eligible studies were recruited, including 12 studies [ 5 , 10 , 11 , 14 , 20 – 27 ] for susceptibility (3321 cases in case group, 3209 cases in control group), whose control groups were in line with HWE balance; 5 [ 5 , 12 – 14 , 28 ] for prognosis, among which 1 [ 28 ] was excluded because of greater heterogeneity, remaining 4 cases (549 cases). The characteristics and genotype distribution of the included analyses are presented in Tables 1 , 2 , and S1.…”

Upregulation of microRNA-96 and its oncogenic functions by targeting CDKN1A in bladder cancer

“…As a major player in mammalian cell cycle progression, CDKN1A inhibits cyclin/cdk2 complexes and plays a crucial role in mediating growth arrest when cells are exposed to DNA damaging agents, implying its tumor suppressive role [ 28 ]. Several factors, including Ap2, BRCA1, C/EBPa, E2F-1/E2F-3, Sp1/Sp3, Smads and STAT, activate the transcription of CDKN1A [ 29 ]. Moreover, CDKN1A is also involved in terminal differentiation, replicative senescence and protection from p53-dependent and -independent apoptosis [ 30 ].…”

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection

“…The anti-SLC39A6 antibody was from Abcam (Cambridge, MA). Immunostaining was assessed as described [16,17]. Tissues showing scores of ≥+ for SLC39A6 staining were defined as positive;…”

“…The assay involved PCR to amplify the DNA, PCR product extension using a single primer, and product identification using MassARRAY SpectroCHIP and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (Sequenom). Data were analyzed using TYPER software (Sequenom) [15][16][17].…”