The effect of raloxifene on Bax protein expression in breast carcinomas of postmenopausal women

Lopes-Costa, Pedro Vitor; Santos, Adaniel Sousa dos; Silva, Benedito Borges da

doi:10.1002/dc.21580

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…The BAX promoter binds to different transcription factors or proteins, such as p53 response elements, the TATA box, canonical E-boxes, and the NF-κB binding site to regulate BAX expression 44 . BAX was extensively studied in different types of cancer such as pancreatic cancer 45 , colon cancer 46 47 , esophageal cancer 48 , lung cancer 49 50 , squamous cell carcinoma of the head and neck 11 , prostate carcinoma 51 , ovarian carcinoma 52 , and breast cancer 53 . Recently, BAX-248G>A (rs4645878) was reported to be associated with reduced expression of BAX protein and altered susceptibility to chronic lymphocytic leukemia 25 26 , although a meta-analysis of seven independent studies with 1772 cases and 1708 controls revealed that neither allele frequency nor genotype of BAX-248G>A associated with risk of human cancer using different genetic models 54 .…”

Section: Discussionmentioning

confidence: 99%

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

Peng

Wang²,

et al. 2015

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 99%

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

Peng

Wang²,

et al. 2015

Sci Rep

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“…In mitochondria mediated apoptotic cell death process Bax acts as an essential gatekeeper as its activation irreversibly commits the most of the cells to die [40,41]. It has been studied extensively on its relationship with different types of cancer, such as pancreatic [19,42], bladder [21], gastric [18], colorectal [43,44], esophageal [16], lung [32,45,46], cervical [47], colon [48,49], prostate carcinoma [50,51], squamous cell carcinoma of the head and neck [36], nasopharyngeal carcinoma [52], breast carcinomas [32,53], ovarian carcinoma [54], renal and transitional cell cancer [55], gliomas [56], CLL [30,31,33–35,38,57], Hodgkin’s lymphoma [17], non-Hodgkin's lymphoma [58], myeloma [59], acute leukemia [60], etc. Bax promoter contains response elements for an important tumor suppressor p53 and this affects gene expression [28].…”

Section: Discussionmentioning

confidence: 99%

Lack of Association between Bax Promoter (-248G>A) Single Nucleotide Polymorphism and Susceptibility towards Cancer: Evidence from a Meta-Analysis

Sahu

Choudhuri

2013

PLoS ONE

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BackgroundThe Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G>A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer.MethodologyWe conducted a search of case-control studies on the associations of Bax-248G>A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE) in controls, power calculation, heterogeneity analysis, Begg’s funnel plot, Egger’s linear regression test, forest plot and sensitivity analysis were performed in the present study.ResultsCancer risk associated with Bax-248G>A polymorphism was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The pooled ORs were calculated in allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive model. Statistical significance was checked through Z and p-value in forest plot. A total of seven independent studies including 1772 cases and 1708 controls were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distributions of this polymorphism were associated with risk for cancer in any of the genetic model. Furthermore, Egger’s test did not show any substantial evidence of publication bias.Conclusions/SignificanceThis meta-analysis suggests that the Bax-248G>A polymorphism is not an important cancer risk factor. Nevertheless, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are required to further validate the results.

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“…The pro-apoptotic roles of the Bax gene to other collaborative genes, such as Bcl-2 and p53, have renewed the interest in Bax gene modifications and the related outcome in cancer. Bax has been widely researched on numerous types of cancers, including pancreatic cancer [54], colon cancer [55,56], esophageal cancer [57,58], pulmonary cancer [59,60], squamous head and neck cancer [61], prostate cancer [62], ovarian cancer [63], and breast cancer [64]. The Bax gene has been involved in the suppression of tumors due to its role in promoting the programmed cell death.…”

Section: Discussionmentioning

confidence: 99%

Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Bcl-2/Bax) and Proinflammatory Cytokine (TNF-α/IL-8) Genes on the Susceptibility and Progression of Myeloproliferative Neoplasms: A Case-Control Biomarker Study

Moawadh

Mir

Tayeb

et al. 2023

CIMB

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The regulation of apoptosis (the programmed cell death) is dependent on the crucial involvement of BCL2 and BAX. The Bax-248G>A and Bcl-2-938 C>A polymorphic variations in the promoter sequences of the Bax and Bcl-2 gene have been recently associated with low Bax expression, progression to advanced stages, treatment resistance, and shortened overall survival rate in some hematological malignancies, including chronic myeloid leukemia (CML) and other myeloproliferative neoplasms. Chronic inflammation has been linked to various stages of carcinogenesis wherein pro-inflammatory cytokines play diverse roles in influencing cancer microenvironment leading to cell invasion and cancer progression. Cytokines such as TNF-α and IL-8 have been implicated in cancer growth in both solid and hematological malignancies with studies showing their elevated levels in patients. Genomic approaches have in recent years provided significant knowledge with the regard to the association of certain SNPs (single nucleotide polymerphisms) either in a gene or its promoter that can influence its expression, with the risk and susceptibility to human diseases including cancer. This study has investigated the consequences of promoter SNPs in apoptosis genes Bax-248G>A (rs4645878)/Bcl-2-938C>A (rs2279115) and pro-inflammatory cytokines TNF-α rs1800629 G>A/IL-8 rs4073 T>A on the risk and susceptibility towards hematological cancers. The study design has 235 individuals both male and female enrolled as subjects that had 113 cases of MPDs (myeloproliferative disorders) and 122 healthy individuals as controls. The genotyping studies were conducted through ARMS PCR (amplification-refractory mutation system PCR). The Bcl-2-938 C>A polymorphism showed up in 22% of patients in the study, while it was observed in only 10% of normal controls. This difference in genotype and allele frequency between the two groups was significant (p = 0.025). Similarly, the Bax-248G>A polymorphism was detected in 6.48% of the patients and 4.54% of the normal controls, with a significant difference in genotype and allele frequency between the groups (p = 0.048). The results suggest that the Bcl-2-938 C>A variant is linked to an elevated risk of MPDs in the codominant, dominant, and recessive inheritance models. Moreover, the study indicated allele A as risk allele which can significantly increase the risk of MPDs unlike the C allele. In case of Bax gene covariants, these were associated with an increased risk of MPDs in the codominant inheritance model and dominant inheritance model. It was found that the allele A significantly enhanced the risk of MPDs unlike the G allele. The frequencies of IL-8 rs4073 T>A in patients was found to be TT (16.39%), AT (36.88%) and AA (46.72%), compared to controls who were more likely to have frequencies of TT (39.34%), AT (37.70%) and AA (22.95%) as such, respectively. There was a notable overrepresentation of the AA genotype and GG homozygotes among patients compared to controls in TNF-α polymorphic variants, with 6.55% of patients having the AA genotype and 84% of patients being GG homozygotes, compared to 1.63% and 69%, respectively in controls. The data from the current study provide partial but important evidence that polymorphisms in apoptotic genes Bcl-2-938C>A and Bax-248G>A and pro-inflammatory cytokines IL-8 rs4073 T>A and TNF-α G>A may help predict the clinical outcomes of patients and determine the significance of such polymorphic variations in the risk of myeloproliferative diseases and their role as prognostic markers in disease management using a case-control study approach.

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The effect of raloxifene on Bax protein expression in breast carcinomas of postmenopausal women

Cited by 4 publications

References 30 publications

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

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

Lack of Association between Bax Promoter (-248G>A) Single Nucleotide Polymorphism and Susceptibility towards Cancer: Evidence from a Meta-Analysis

Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Bcl-2/Bax) and Proinflammatory Cytokine (TNF-α/IL-8) Genes on the Susceptibility and Progression of Myeloproliferative Neoplasms: A Case-Control Biomarker Study

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