Polymorphism In Breast Cancer Research Articles

Interleukin 1 Alpha Gene Polymorphism in Breast Cancer After Chemotherapy Treatment

Abstract Background: The interleukin 1 (IL-1) family of cytokines is essential for triggering and controlling immunological and inflammatory responses. We believe the levels of these cytokines in breast tumor homogenates relate to other known prognosticators of patient survival. Objectives: The association between the risk of breast tumors and the IL-1 alpha −889 C>T Promoter Primer polymorphism has been established. Interleukin 1 alpha −889 C>T Promoter Primer has been proven to influence breast tumor susceptibility. Our research aimed to determine whether the IL-1 alpha −889 C>T Promoter Primer gene polymorphism and susceptibility to Breast cancers (BCs) are related. Materials and Methods: The genotype frequencies of the IL-1 alpha −889 C>T Promoter Primer polymorphism were compared between 100 BC cases and 50 controls with the assistance of polymerase chain reaction and restriction fragment length polymorphism techniques. Additional multivariate binary logistic regression analyses were carried out to determine the level of IL-1 in patients’ blood and to examine the association between the IL-1 alpha −889 C>T Promoter Primer polymorphism and BC risk utilizing the ELISA technique after therapy. Results: The concentration of CA 15-3 in patients with BC was 101.107 increase significantly compare with mean of control group was 62.802, in chemotherapy patients genotype frequencies of TT, CT, CC of IL-1 alpha −889 C>T gene polymorphism where it patients with genotype TT were affected by breast tumors approximately one time comparison with patients having genotype CT (odd ratio = 1.50 and 0.91). Conclusion: Concentration of CA 15-3 increase in patients after chemotherapy compared with healthy, The IL-1 alpha −889 C>T polymorphism affects breast tumors in women.

Genetic Polymorphism in FSCN1 rs3801004 C/G and CD44 rs353639 A/C, as Prognostic Factor in Egyptian Breast Cancer Patients.

One of the main causes of cancer-related deaths is breast cancer. Fascin-1(FSCN1) is an actin-binding protein that is present in the mesenchymal, neuronal, and endothelial cells of mammals. Patients with breast cancer have been found to have FSCN1 overexpression. CD44 is crucial for the development, invasion, and tumour spread. Therefore, we aimed to investigate the role of FSCN1&CD44 gene polymorphisms in breast cancer (BC) risk and prognosis. A total of 96 BC patients and 50 controls were included in the case-control study for risk prediction. We examined the association between The SNPs on FSCN1(rs3801004) and CD44(rs353639) and BC susceptibility and clinicopathological features using a real-time PCR in a cohort of the Egyptian population. Results: A significant association of both SNPs on FSCN1(rs3801004)C allele and CD44(rs353639)A allele and BC susceptibility(adjusted OR=4.38,95%CI:2.6-7.4,p<0.001, and adjusted OR=4.44,95%CI:2.65-7.44,p <0.001,respectively). Moreover, CC genotype in FSCN1(rs3801004) were likely to progress to developing G2&G3 and N2&N3 and stage II & stage IV, according to the TNM staging and GG+GC genotypes increased within individuals who had a positive family history of BC. Individuals who carry at least one A allele for CD44rs353639 were likely to progress developing N2 according to the TNM in BC patients. These findings suggest that both SNPs on FSCN1 (rs3801004) and CD44 (rs353639) affected BC susceptibility. FSCN1 (rs3801004) genetic variants may have a significant effect on BC prognosis. However, CD44 (rs353639) affected lymph node invasions in BC patients.

Association of MMP1 gene polymorphisms with breast cancer risk: A narrative review.

Breast cancer is a multifactorial malignancy with different clinicopathological and molecular characteristics. It is the most frequent cancer in women in terms of both incidence and mortality. Matrix metallopeptidase 1 or MMP1 is a zinc-dependent endopeptidase associated with several physiological processes through the modification of the extracellular matrix and tumor microenvironment. However, previous results did not suggest any concluding remarks on the correlation between MMP1 gene polymorphisms and the risk of breast cancer. A comprehensive literature search was performed in PubMed database to retrieve relevant articles and extract data from suitable ones. The literature written only in English was selected for this review. A total of 26 articles were included in the present narrative review. From the available studies, it is observed that MMP1 is upregulated in breast cancer tissues and found to be correlated with metastasis and invasion. The expression of MMP1 gene is mediated by numerous factors, including polymorphisms which act as a potential risk factor for the progression of breast cancer. To establish the correlation between genetic polymorphisms in MMP1 and the risk of breast cancer, several case-control studies, as well as genetic analyses, have been carried out in different ethnicities. The association of genetic polymorphisms in MMP1 with the risk and survival of breast cancer in different populations has been reviewed in this study. Moreover, the structural domain of MMP1 and the role of MMP1 in breast cancer metastasis and invasion are also discussed which will help to understand the potential impact of MMP1 as a genetic biomarker. This review provides an overview of the MMP1 gene polymorphisms in breast cancer. However, we recommend future studies concentrating on combined analysis of multiple SNPs, gene-gene interactions, and analysis of epigenetics, proteomics, and posttranscriptional modifications that will provide the best outcome.

Case Report: The Relationship of CCND1 RS614367 Polymorphism with Clinicopathological Features

Recent studies have shown that the CCND1 rs614367 polymorphism increases the risk of breast cancer and its invasive nature. However, studies evaluating the relationship of the CCND1 rs614367 polymorphism based on the clinicopathology of breast cancer patients in Indonesia were still limited. This study is aimed to determine the CCND1 rs614367 polymorphism in breast cancer and its relationship with the patient's clinicopathology. Methods: This study was a cross-sectional study on 45 samples of breast cancer patients. After collecting demographic and clinical data, PCR and sequencing will be performed on all blood samples to determine the CCND1 rs614367 polymorphism. All variables that have been collected will be analyzed using SPSS version 25.0 to determine the relationship between the CCND1 rs614367 polymorphism and the clinicopathology of breast cancer patients. The CCND1 rs614367 gene polymorphism in breast cancer subjects showed that 25 (55.5%) and 20 (44.5%) subjects had C and T alleles. Subjects aged ≥ 50 years old had a significant 4.45 risk of having the T allele type (p=0.037). In addition, subjects with metastases (M1) were also at a significant 4.89 times risk of having the T allele type (p=0.015). Subjects with histological grade III also had a significantly 4.77 times risk of having the T allele type (p=0.013). In conclusion, there was a significant relationship between CCND1 rs614367 polymorphism and breast cancer subjects' clinopathology features (age, metastasis, and grade). More than half of the subjects with this polymorphism had the C allele.

Hypoxia-Inducible Factors-Based Single Nucleotide Polymorphism in Breast Cancer with More Cancer Susceptibility.

Hypoxia-inducible factors (HIFs) are a collection of transcriptional factors that engage in the regulation of oxygen homeostasis. They are hypoxia-responsive stress factors whose expression is linked to tumor growth and angiogenesis. HIF is a crucial player in the progression of breast cancer. Patients with high levels of hypoxia-inducible HIFs in their primary tumor biopsies had a higher chance of metastasis, the leading cause of breast cancer-related death. HIF polymorphisms have been shown in several epidemiological studies to influence breast cancer susceptibility. In the oxygendependent degradation domain, several short nucleotide polymorphisms (SNPs) of the HIF gene have been connected with higher HIF activity. To find SNP that make up the genetic diversity that underpins the phenotypic difference found between individuals in their susceptibility to cancer and the course of their disease, researchers used a variety of potential pathway-based approaches.

The association between genetic variation rs2292832 and the processing efficiency of pre-mir-149 affects the risk of breast cancer.

microRNAs (miRNAs) play key roles in regulating cancer development, including breast cancer. Variation in miRNA genes can associate with the risk of cancer by alterations in the miRNA's processing and maturation. Therefore, human blood samples and breast cancer cell line (MCF7) were analyzed to study any possible association between the genetic variant (rs2292832) in the miR-149 precursor and breast cancer susceptibility. To study the role of rs2292832 polymorphism in breast cancer, the miR-149 gene variant was genotyped using PCR-RFLP. For evaluating the effect of SNP on function and expression levels of mature miR-149, we inserted pre-miR-149 and flanking region with CC or TT genotype into a pEGFPN1 expression vector, and qPCR was accomplished. Cell survival, proliferation, and migration properties investigated by MTT and wound healing assay. Statistical analysis was carried out for data analysis. T allele in variant rs2292832 is associated with an increased risk of breast cancer. Such association was also obtained in co-dominant (OR = 2.5) and dominant (OR = 2.016) models. The variant allele led to reduced production of mature miR-149 and resulted in increased cell proliferation and migration of MCF7 cells. These findings suggest that miR-149 suppresses tumor cell proliferation, and the pre-mir-149 polymorphism affects the processing of miR-149, causing an alteration in the abundance of the miRNA mature form, which can regulate tumor progression and metastasis.

Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphisms in breast cancer: A Filipino preliminary case-control study

Single nucleotide polymorphisms (SNP) present in folate metabolic enzymes, such as methylenetetrahydrofolate reductase (MTHFR), affect DNA synthesis and methylation processes that can lead to cancer development. Several studies suggest that MTHFR SNP is associated with breast cancer risk, particularly among Asian populations. Thus, this study determined the association of MTHFR 677C>T SNP with breast cancer risk in selected Filipino population. DNA samples from breast cancer cases (n = 100) and clinically healthy controls (n = 100) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The differences in MTHFR genotype and allele frequencies were evaluated by computing for the odds ratio (OR) with a 95 % confidence interval (CI). The CT genotype (OR: 0.775, 95 % CI: 0.35–1.71, p = 0.53), T allele (OR: 0.703, 95 % CI: 0.34–1.48, p = 0.35), and presence of at least one T allele (ORCT+TT: 0.729, 95 % CI: 0.33–1.60, p = 0.43) were not associated with breast cancer risk. Based on the SNP interaction with other risk factors, no significant difference (p > 0.05) was observed for the tumor characteristics, menarche age, and menopause age. Interestingly, a decreased risk (OR: 0.342, 95 % CI: 0.14–0.84, p = 0.019) was observed for the CC genotype in individuals who consumed dietary fibers. Meanwhile, there was an increased risk for passive smokers with the CC genotype (OR: 6.31, 95 % CI: 2.68–14.9, p < 0.001). Overall, the MTHFR 677C>T was not significantly associated with breast cancer risk in a selected Filipino population. Since this study involved a relatively small number of participants, increasing the number of samples is recommended for a more conclusive test of association of MTHFR 677C>T with breast cancer risk in Filipinos.

Association between the rs4784227-CASC16 polymorphism and the risk of breast cancer: A meta-analysis.

Objective:Although several studies have identified an association between the rs4784227-cancer susceptibility candidate gene 16 (CASC16) polymorphism and breast cancer, the results remain inconclusive. Therefore, we conducted a meta-analysis to assess the relationship between the rs4784227-CASC16 polymorphism and breast cancer risk.Methods:Studies were searched in the PubMed, Web of Science, Embase, Google Scholar, and Cochran Library databases until June 10, 2021, to identify all potential literature on rs4784227-CASC16 polymorphism and breast cancer risk association. Fixed-effect or random-effect models were used to calculate odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Subgroup analyses, publication bias, and sensitivity analyses were also conducted.Results:Seventeen eligible studies involving 34,719 subjects (18,445 cases and 16,274 healthy controls) from 7 articles were included in the current meta-analysis. The pooled ORs regarding the association between the rs4784227-CASC16 polymorphism and breast cancer risk were statistically significant [T vs C: OR = 1.244, 95% CI = 1.202–1.287; TT vs CT + CC: OR = 1.407, 95% CI = 1.296–1.528; CC vs CT + TT: OR = 0.777, 95% CI = 0.745–0.811; TT vs CC: OR = 1.544, 95% CI = 1.419–1.681; CT vs CC: OR = 1.244, 95% CI = 1.189–1.301]. On subgroup analysis, the rs4784227-CASC16 T/C gene has a certain correlation with breast cancer susceptibility in Asian and North American populations, but no significant risk in the Australian population.Conclusion:Our pooled analysis showed a significant association between the rs4784227- (T) allele and breast cancer susceptibility in Asian and North American populations, and intervention with this mutation might be a new therapeutic strategy for breast cancer. However, large-scale and well-designed studies are needed in different populations to further evaluate the role of the rs4784227-CASC16 polymorphism in breast cancer.

The effect of survivin gene in breast cancer risk and prognosis

Abstract Objectives The accumulation of genetic damages in onset of cancer induce activation of protooncogenes or inactivation of tumor suppressor genes thus cause disruption of the balance between cell proliferation and programmed cell death. As a member of the apoptosis inhibitory protein family (IAP), survivin play important roles in carcinogenesis process. The evidence suggests that polymorphisms located in survivin promoter region may be important in determining genetic susceptibility of cancer. In this study, we aimed to examine a possible role of survivin −31 and −625 G/C gene polymorphisms in breast cancer. Methods A total of 160 breast cancer cases and 153 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results Genotype and allele distributions and of −31 and −625 G/C polymorphisms were not significantly different between two groups. However, we observed the carriers of survivin −625 C/G polymorphism homozygous genotypes (GG/CC) were the significantly higher in patients with tumor necrosis (p=0.047). Conclusions Our results suggest that survivin −625 C/G polymorphism may be related with tumor prognosis, but we are opinion of that our result require to be validated in larger samples and further comprehensive research may explore the correlation.

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression

Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97–1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10−12) but not in the rest of breast cancer subtypes.

Effects of methylenetetrahydrofolate reductase single-nucleotide polymorphisms on breast, cervical, ovarian, and endometrial cancer susceptibilities

BackgroundRecent studies identifying methylenetetrahydrofolate reductase (MTHFR) polymorphisms associated with breast cancer (BC), ovarian cancer (OC), cervical cancer, and endometrial cancer (EC) have reported conflicting results and been underpowered. To clarify the correlation between MTHFR mutations and these common female malignancies, we conducted a comprehensive meta-analysis incorporating all eligible publications. MethodsRelevant reports published before January 20, 2020, were retrieved from PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval summaries for the MTHFR 677C/T and 1298A/C polymorphisms in BC, OC, cervical cancer, and EC were estimated. ResultsA total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included. The results showed a markedly elevated risk of cancer susceptibility related to MTHFR 677C/T based on all genetic models. Similarly, we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models, except the heterozygous model. Moreover, subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models. Based on ethnicity, significant associations were observed between Asian, African, and mixed populations for 677C/T and the Asian population for 1298A/C. With regard to the sample type used for analysis, we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models. Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method, as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C, respectively. ConclusionThis meta-analysis suggests that MTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers, with these findings potentially applicable for overall comparisons of related data.

Correlation between rs13347 polymorphism of CD44 gene and the risk of occurring breast cancer: A protocol for systematic review and meta-analysis.

Background:With the attention paid to the heritability of breast cancer, the search for the genetic susceptibility gene of breast cancer has become a hot spot. At present, a number of studies have explored the relationship between rs13347 polymorphism of cluster of differentiation 44 (CD44) gene and breast cancer, but the research conclusions are inconsistent. Therefore, we will use this meta-analysis to explore the role of this gene polymorphism in breast cancer susceptibility.Methods:The search time is set from the establishment of the database in March 2021 in this study. The search database include China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and China Biology Medicine disc, PubMed, EMBASE, Web of Science and the Cochrane Library. The subjects are observational studies on the relationship between rs13347 polymorphism of CD44 gene and breast cancer (including case-control study, cross-sectional study and a cohort study). The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by two researchers independently. The data are statistically analyzed by Stata 16.0 software.Results:Based on the existing studies, this study will systematically evaluate the relationship between CD44 gene rs13347 polymorphism and breast cancer.Conclusion:This study will provide evidence-based medical evidence to clarify the role of CD44 gene polymorphism in breast cancer, and provide help for the early detection and preventive intervention of breast cancer.Ethics and dissemination:Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/WBC7F

Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer.

Mutations and polymorphisms in genes of cell- cycle and apoptosis regulatory pathway influence the breast cancer risk. Analysis of single low penetrance mutant alleles may not reflect the precise risk association when analyzed alone. A total of 115 DNA samples extracted from breast cancer patients and an equal number of age and sex-matched normal controls were used for polymorphic analysis. Genotyping for p21 rs1801270 and CCND1 rs603965 was done by PCR-RFLP method while AFLP method was used for p53 rs1042522 single nucleotide polymorphism detection. Statistical methods included simple mean±SD and correlation coefficient to analyze the risk of association of p21, p53 and CCND1 SNPs and breast cancer. Individuals harboring SNPs in p21, p53 and CCND1 genes namely rs1801270, rs1042522 and rs603965, respectively were rendered increasingly susceptible to developing breast cancer when compared with normal controls. Our report emphasizes the need of combinational analysis of low-penetrance mutant alleles to assess accurately their association with breast cancer risk. Future case-control studies analyzing gene-environment interactions across different populations may confirm reported risk associations of studied polymorphisms with developing breast cancer.

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review.

Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.

Polymorphisms in genes involved in breast cancer among Iranian patients.

This review gives a summary of the important genetic polymorphisms in breast cancer with a focus on people in Iran. Several single nucleotide polymorphisms were considered as breast cancer susceptibility polymorphisms within genes (STK15, ERRs, ESR1, p53, SEP15, AURKA, SHBG, SRC, FAS, VEGF, XRCC1, GST, NFκB1, XPC, XRCC3, sirtuin-3, NKG2D).Cytosine-adenine repeat (IGF-I), rs3877899, G-2548A, GGC (eRF3a/GSPT1), IVS2nt-124A/G have shown an increased risk of breast cancers and a decreased risk has been observed in 4G/5G (PAI-1), rs6505162, tri-nucleotide (GCGTGFBR1). We observed that the signaling pathways and antioxidant related genes are the main molecular processes associated with breast cancer progression. Further studies on types of polymorphisms in breast cancer could validate the prognostic value of biomarkers.

Design and characterization of a SYBR Green I-based melting curve method for investigation of HER2I655V polymorphism in breast cancer

BackgroundBreast cancer is a disease in which cell grows rapidly forming a mass in the breast. HER2 polymorphisms Ile655Val have been studied as biomarkers for breast cancer and may comprise a risk factor of cardiac toxicity for breast cancer-consuming trastuzumab. Aim of work: In this study, we developed a simple, low cost, and rapid test to detect polymorphism at HER2 gene using SYBR Green I-based melting curve method. Subjects and methodsIn this report, we performed allelic discrimination with real-time temperature melting (Tm) Shift SYBR Green I-based melting curve method. The melting profiles of amplified DNA HER-2 Ile655Val and its characteristics were analyzed. ResultTm value of HER2 GG and AA alleles were 85 ± 0.14 °C and 82.5 ± 0.23 °C, respectively, while cycle threshold (Ct) value of GG, AG, and AA alleles were 19.6 ± 0.27, 22.5 ± 0.23, 18.6 ± 0.22 correspondingly; furthermore, no template control has shown consisting Ct value at 31.18 ± 0.27. The developed methods’ characteristics were optimum annealing at 62 °C and Kappa coefficient value 1 with the mean almost consistent with PCR-sequencing. The coefficient of variability for intra-assay of GG, AG, and AA was in the range of 0.2–1%, while the coefficient of variability for inter-assay for each were in the range 0.7–1%. Further, based on PCR, shelf-life assay has shown stability for 3 months of storage observation. ConclusionThis approach may be considered as simple, rapid, and low cost supporting the rapid study of HER2 epidemiology. Furthermore, the developed methods potentially facilitate clinicians in dealing with breast cancer patients, especially in considering about the cardiotoxicity effect of trastuzumab.

Polymorphic Variants in 5'-UTR Regions of the RAD51 Gene are Associated With RAD51 Expression and Triple-Negative Breast Cancer (TNBC): A Case-Control Study.

Breast cancer is a heterogeneous disease at morphologic and molecular levels, which is considered the most commonly occurring cancer in women. RAD51, a DNA-repairing protein, involves homologous recombination and has a vital role in genome stability. Polymorphism of the RAD51 gene, and its overexpression, has been proposed to be associated with the development of breast cancer. Overexpression of RAD51 in many types of human cancer including metastatic breast cancer may signify its potential use as a biomarker. Considering the numerous reports on the role of the 5'-UTR-RAD51 polymorphism in breast cancer, this study aimed to investigate the utility of RAD51 gene expression and its variants G135C and G172T as a possible foretelling factor of breast cancer development. DNA sequencing and immunohistochemistry of RAD51 were conducted on 103 samples from patients diagnosed with sporadic breast cancer and 80 samples from a control group. The results demonstrated that the RAD51 variants, G135C and G172T, were significantly presented in the breast cancer tissue compared with the control group. RAD51 expression was mainly shown in the cytoplasm of malignant cells (56% of cases) and significantly correlated with p53 and G135C, C135C variants. Moreover, the occurrence of the G172T variant was significantly associated with the expression of estrogen receptor. Interestingly, 21/26 (81%) of the triple-negative breast cancer showed G135C and C135C genotypes that were significantly associated with the expression of RAD51 (73%). In conclusion, the G135C and C135C variants together with the cytoplasmic expression of RAD51 may have clinical potential as a prognostic predictor for breast cancer development and aggressiveness.

Vitamin D Receptor (VDR) polymorphism and antiproliferative activity of cholecalciferol in cancer cells

Vitamin D (VD) is a steroid hormone with multiple biological functions in the body and its activity requires the binding to the receptor named VDR. VDR polymorphisms seems to be involved in the development of several types of cancer. Herein we performed the genotyping of two VDR polymorphisms (Fok I and Taq I) in MCF-7 breast cancer and U87-MG glioblastoma (GBM) cell lines and investigated the antiproliferative effect of the VD analog cholecalciferol. Polymorphisms were identified by PCR-RFLP and the effect of VD was determined by viability and clonogenic assays. VD inhibited the growth of both tumor cells in vitro. MCF-7 cells were more sensitive than U87-MG cells at concentrations ranging from 0.1nM to 1000nM. The same primer pairs used for PCR amplification of VDR gene in MCF-7 failed to amplify a fragment of expected size in the U87-MG cell line. VDR Fok I and Taq I polymorphisms in breast cancer MCF-7 cells were characterized as FF (CC) and TT respectively. The absence of amplification of VDR gene fragment in U87-MG suggests a possible chromosomal rearrangement and/or impairment of gene expression of VDR which could interfere in the sensitivity of this cell line to vitamin D.

Receptor for advanced glycation end-product rs1800624 polymorphism contributes to increase breast cancer risk: Evidence from a meta-analysis.

Background:Although several studies have identified an association between the receptor for advanced glycation end-product (RAGE) rs1800624 polymorphism and breast cancer, the results have been conflicting. Therefore, we conducted a meta-analysis to assess the relationship between the RAGE rs1800624 polymorphism and breast cancer risk.Methods:Studies were searched in the PubMed, Web of Science, Embase, Wanfang Med Online, and China National Knowledge Infrastructure databases until September 20, 2019 to identify all potential literature on this association. Fixed-effect or random-effect models were used to calculate odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Subgroup and sensitivity analyses and tests for publication bias were also performed.Results:Five eligible studies involving 2823 subjects (1410 patients and 1413 healthy controls) were included in the current meta-analysis. The pooled analysis indicated a positive correlation between the RAGE rs1800624 polymorphism and the risk of breast cancer in a homozygous genetic model (OR = 1.423, 95% CI = 1.043–1.941, P = .026). Ethnicity-based subgroup analysis demonstrated that RAGE rs1800624 polymorphism may increase the risk of breast cancer in the Asian population in homozygous model (OR = 1.661, 95% CI = 1.178–2.342, P = .004).Conclusion:The RAGE rs1800624 polymorphism may increase the risk of breast cancer in the homozygous genetic model, especially in Asian populations. Large-scale and well-designed studies are needed in different populations to further evaluate the role of the RAGE polymorphism in breast cancer.

Correlation between P53 Arg72Pro and MDM4 gene rs4245739 polymorphisms in breast cancer

BackgroundMDM4 is a negative regulator of p53 tumor suppression pathway. Various studies reveal the fact that the rs4245739A>C polymorphism of MDM4 in 3′-untranslated region is targeted by miR-191 which leads to lower MDM4 expression. On the other hand, the importance of Arg72Pro polymorphism of p53 in breast cancer is proven. The aim of this study is to present the correlation between the aforementioned SNPs and the risk of breast cancer. The statistical society of the study includes 199 healthy women as the control group and 206 women suffering from breast cancer included from Turkish population of the East Azarbaijan. ResultsAlleles of both positions are detected through Tetra-ARMS PCR while SPSS and the SHEsis, online software was exerted for allele typing, genotyping, and haplotype analysis. Different alleles of both MDM4 rs4245739 and p53 Arg72Pro had no significant frequency in patients (P > 0.05). Furthermore, genotypes of neither MDM4 rs4245739 nor p53 Arg72Pro could increase or decrease the risk of breast cancer in patients compared to healthy women. Additionally, a significant factor affecting the risk of breast cancer is gene-gene interaction. The results of the ongoing study revealed that two genetic variants, MDM4 rs4245739 and p53 Arg72Pro polymorphisms, failed to be associated, individually and combined together, with the risk of breast cancer. However, additional well-designed studies on large populations are required to validate such an association. ConclusionVarious alleles of both SNPs had no significant frequency difference between patients and controls. Moreover, genotypes of neither MDM4 nor p53 were significantly distributed in women with breast cancer compared to the healthy controls. Meanwhile, haplotype analysis failed to be significant. Last but not least, all clinical manifestations, other than association between tumor size and MDM4 genotypes could not be correlated with either various alleles or genotypes.