Polymorphisms of BCL2 and BAX Genes Associate with Outcomes in Advanced Non-small cell lung cancer Patients treated with platinum-based Chemotherapy

Abstract

Single-nucleotide polymorphisms (SNP) of the gene belonging to the BCL2 family are thought to play a role in chemotherapy resistance. This study investigated the association of BCL2-938C>A(rs2279115) and BAX-248G>A(rs4645878) promoter region SNPs and the clinical responses and outcomes of 235 non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. The data suggested that BAX-248GA and GA+AA genotype was associated with poor response [odds ratio (OR) 1.943, p = 0.039; OR 1.867, p = 0.038, respectively] to chemotherapy, and BCL2-938CA, CA+AA and BAX-248GA, AA and GA+AA were associated with poor progression-free survival (PFS) [hazard ratio (HR) 1.514, p = 0.004; HR 1.456, p = 0.009; HR 1.449, p = 0.013; HR 2.006, p = 0.010; HR 1.506, p = 0.003, respectively] and BCL2-938CA, AA and CA+AA and BAX-248GA, AA and GA+AA were associated with poor overall survival (OS) (HR 2.006, p < 0.001; HR 2.322, p < 0.001; HR 2.096, p < 0.001; HR 1.632, p = 0.001; HR 2.014, p = 0.010; HR 1.506, p < 0.001, respectively). Furthermore, combination of these two polymorphisms showed patients with 2–4 variant alleles of these two genes associated with poor PFS and OS (HR 1.637, p = 0.001; HR 2.365, p < 0.001). The data from the current study provide evidence that BCL2-938C>A and BAX-248G>A polymorphisms may be useful in predicting clinical outcomes of patients with advanced inoperable NSCLC to platinum-based chemotherapy.

MicroRNA‑137‑regulated AKT serine/threonine kinase 2 inhibits tumor growth and sensitizes cisplatin in patients with non‑small cell lung cancer

“…Bax is an important regulatory factor of apoptosis. The Bax gene belongs to the B cell lymphoma-2 family and serves a role in the promotion of apoptosis (26). The results of the present study demonstrated that the overexpression of microRNA-137 significantly induced the expression of Bax protein in A549 and H520 cells treated with cisplatin.…”

A genome‐scale CRISPR knock‐out screen in chronic myeloid leukemia identifies novel drug resistance mechanisms along with intrinsic apoptosis and MAPK signaling

“…Our screening procedure was robust as a subset of the highly ranked genes (BAX, BIM, BAP1, and SPRED2) had previously been correlated to either CML progression, imatinib resistance, or resistance to alternative therapies in different cancer types. 24,[34][35][36][37] Gene set enrichment and STRING DB analyses unveiled cellular processes that seem crucial for optimal imatinib-induced cell death such as genes involved in intrinsic apoptosis.…”

Genetic determinants for chemo- and radiotherapy resistance in bladder cancer

“…These results suggest that Bfl-1/A1 might play a crucial role in the suppression of the apoptosis Bfl-1/A1 by TNF-α, p53, B cell antigen receptor ligation and Bax and induce resistance to chemotherapeutics. The BCL2-938C>A (rs2279115) and BAX-248G>A (rs4645878) promoter region SNPs were associated with poor progression-free survival in patients with NSCLC ( 79 ). To our knowledge, no study reported polymorphisms of the bcl-2 family protein associated with worse prognosis in patients with BCa.…”