Displaying publications 1 - 20 of 178 in total

Abstract:
Sort:
  1. Genetic polymorphisms of TP53-binding protein 1 (TP53BP1) gene and association with breast cancer risk
    Naidu R, Har YC, Taib NA
    APMIS, 2011 Jul;119(7):460-7.
    PMID: 21635553 DOI: 10.1111/j.1600-0463.2011.02753.x
    In the present study, we evaluated the association between the TP53BP1 Glu353Asp and T-885G polymorphisms and breast cancer risk as well as with the clinicopathological characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using PCR-RFLP method in a hospital-based Malaysian population. Breast cancer risk was not observed among women who were heterozygous (OR(adj) = 0.887; 95% CI, 0.632-1.245) or homozygous (OR(adj) = 1.083; 95% CI, 0.595-1.969) for Asp allele, and those carriers of Asp allele (OR(adj) = 0.979; 95% CI, 0.771-1.243). Similarly, women who were TG heterozygotes (OR(adj) = 1.181; 95% CI, 0.842-1.658) or GG homozygotes (OR(adj) = 1.362; 95% CI, 0.746-2.486) and carriers of G allele (OR(adj) = 1.147; 95% CI, 0.903-1.458) were not associated with increased risk of breast cancer. Asp allele genotype was significantly associated with ER negativity (p = 0.0015) and poorly differentiated tumours (p = 0.008), but G allele genotype was not associated with the clinicopathological characteristics. In conclusion, Glu353Asp and T-885G polymorphic variants might not have an influence on breast cancer risk, thus might not be potential candidates for cancer susceptibility. Glu353Asp variant might be associated with tumour aggressiveness as defined by its association with ER negativity and poorly differentiated tumours.
    Matched MeSH terms: Breast Neoplasms/genetics*
  2. The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients
    Saleem M, Ghazali MB, Wahab MAMA, Yusoff NM, Mahsin H, Seng CE, et al.
    Adv Exp Med Biol, 2020;1292:1-12.
    PMID: 29687286 DOI: 10.1007/5584_2018_147
    Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.
    Matched MeSH terms: Breast Neoplasms/genetics*
  3. Fulltext Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk
    Kramer I, Hooning MJ, Mavaddat N, Hauptmann M, Keeman R, Steyerberg EW, et al.
    Am J Hum Genet, 2020 11 05;107(5):837-848.
    PMID: 33022221 DOI: 10.1016/j.ajhg.2020.09.001
    Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
    Matched MeSH terms: Breast Neoplasms/genetics*
  4. Fulltext Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element
    Baxter JS, Johnson N, Tomczyk K, Gillespie A, Maguire S, Brough R, et al.
    Am J Hum Genet, 2021 Jul 01;108(7):1190-1203.
    PMID: 34146516 DOI: 10.1016/j.ajhg.2021.05.013
    A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
    Matched MeSH terms: Breast Neoplasms/genetics
  5. Fulltext Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1
    Glubb DM, Maranian MJ, Michailidou K, Pooley KA, Meyer KB, Kar S, et al.
    Am J Hum Genet, 2015 Jan 08;96(1):5-20.
    PMID: 25529635 DOI: 10.1016/j.ajhg.2014.11.009
    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.
    Matched MeSH terms: Breast Neoplasms/genetics*
  6. Fulltext Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression
    Darabi H, McCue K, Beesley J, Michailidou K, Nord S, Kar S, et al.
    Am J Hum Genet, 2015 Jul 02;97(1):22-34.
    PMID: 26073781 DOI: 10.1016/j.ajhg.2015.05.002
    Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.
    Matched MeSH terms: Breast Neoplasms/genetics*
  7. Fulltext Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation
    Ghoussaini M, French JD, Michailidou K, Nord S, Beesley J, Canisus S, et al.
    Am J Hum Genet, 2016 Oct 06;99(4):903-911.
    PMID: 27640304 DOI: 10.1016/j.ajhg.2016.07.017
    Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER+) breast cancer (per-g allele OR ER+ = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10-30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER-) breast cancer (lead SNP rs6864776: per-a allele OR ER- = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10-12), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10-05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.
    Matched MeSH terms: Breast Neoplasms/genetics*
  8. BRCA1 c.2845insA is a founder mutation in Singaporean Malay women with early onset breast/ovarian cancer
    Sng JH, Ali AB, Lee SC, Zahar D, Wong JE, Cross G, et al.
    Ann Acad Med Singap, 2003 Sep;32(5 Suppl):S53-5.
    PMID: 14968737
    Matched MeSH terms: Breast Neoplasms/genetics*
  9. Apoptosis induced by desmethyl-lasiodiplodin is associated with upregulation of apoptotic genes and downregulation of monocyte chemotactic protein-3
    Hazalin NA, Lim SM, Cole AL, Majeed AB, Ramasamy K
    Anticancer Drugs, 2013 Sep;24(8):852-61.
    PMID: 23764760 DOI: 10.1097/CAD.0b013e3283635a47
    There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.
    Matched MeSH terms: Breast Neoplasms/genetics
  10. 1'S-1'-acetoxyeugenol acetate: a novel phenylpropanoid from Alpinia conchigera enhances the apoptotic effects of paclitaxel in MCF-7 cells through NF-κB inactivation
    In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Anticancer Drugs, 2011 Jun;22(5):424-34.
    PMID: 21346553 DOI: 10.1097/CAD.0b013e328343cbe6
    In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.
    Matched MeSH terms: Breast Neoplasms/genetics
  11. Xanthorrhizol exhibits antiproliferative activity on MCF-7 breast cancer cells via apoptosis induction
    Cheah YH, Azimahtol HL, Abdullah NR
    Anticancer Res, 2006 Nov-Dec;26(6B):4527-34.
    PMID: 17201174
    Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza Roxb (Zingiberaceae). Xanthorrhizol was tested for a variety of important pharmacological activities including antioxidant and anti-inflammatory activities. An antiproliferation assay using the MTT method indicated that xanthorrhizol inhibited the proliferation of the human breast cancer cell line, MCF-7, with an EC50 value of 1.71 microg/ml. Three parameters including annexin-V binding assay, Hoechst 33258 staining and accumulation of sub-G1 population in DNA histogram confirmed the apoptosis induction in response to xanthorrhizol treatment. Western-blotting revealed down-regulation of the anti-apoptotic bcl-2 protein expression. However, xanthorrhizol did not affect the expression of the pro-apoptotic protein, bax, at a concentration of 1 microg/ml, 2.5 microg/ml and 5 microg/ml. The level of p53 was greatly increased, whilst PARP-1 was cleaved to 85 kDa subunits, following the treatment with xanthorrhizol at a dose-dependent manner. These results, thereby, suggest that xanthorrhizol has antiproliferative effects on MCF-7 cells by inducing apoptosis through the modulation of bcl-2, p53 and PARP-1 protein levels.
    Matched MeSH terms: Breast Neoplasms/genetics
  12. Is BRCA Mutation Testing Cost Effective for Early Stage Breast Cancer Patients Compared to Routine Clinical Surveillance? The Case of an Upper Middle-Income Country in Asia
    Lim KK, Yoon SY, Mohd Taib NA, Shabaruddin FH, Dahlui M, Woo YL, et al.
    Appl Health Econ Health Policy, 2018 06;16(3):395-406.
    PMID: 29572724 DOI: 10.1007/s40258-018-0384-8
    OBJECTIVE: Previous studies showed that offering BRCA mutation testing to population subgroups at high risk of harbouring the mutation may be cost effective, yet no evidence is available for low- or middle-income countries (LMIC) and in Asia. We estimated the cost effectiveness of BRCA mutation testing in early-stage breast cancer patients with high pre-test probability of harbouring the mutation in Malaysia, an LMIC in Asia.

    METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.

    RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.

    CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.

    Matched MeSH terms: Breast Neoplasms/genetics*
  13. Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression
    Hooshmand S, Ghaderi A, Yusoff K, Thilakavathy K, Rosli R, Mojtahedi Z
    Asian Pac J Cancer Prev, 2014;15(7):3311-7.
    PMID: 24815488
    BACKGROUND: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest.

    MATERIALS AND METHODS: ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα.

    RESULTS: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells.

    CONCLUSIONS: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

    Matched MeSH terms: Breast Neoplasms/genetics*
  14. Quantification of Her-2/Neu gene in breast cancer patients using real time-polymerase chain reaction (Q-PCR) and correlation with immunohistochemistry findings
    Abdul Murad NA, Razak ZA, Hussain RM, Syed Hussain SN, Ko Ching Huat C, Che Md Ali SA, et al.
    Asian Pac J Cancer Prev, 2013;14(3):1655-9.
    PMID: 23679251
    BACKGROUND: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR).

    MATERIALS AND METHODS: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification.

    RESULTS: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR.

    CONCLUSION: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.

    Matched MeSH terms: Breast Neoplasms/genetics
  15. Microarray and quantitative PCR analysis of gene expression profiles in response to treatment with tomato leaf extract in mcf-7 breast cancer cells
    Amid A, Wan Chik WD, Jamal P, Hashim YZ
    Asian Pac J Cancer Prev, 2012;13(12):6319-25.
    PMID: 23464452
    We previously found cytotoxic effects of tomato leaf extract (TLE) on the MCF-7 breast cancer cell line. The aim of this study was to ascertain the molecular mechanisms associated with the usage of TLE as an anticancer agent by microarray analysis using mRNA from MCF-7 breast cancer cells after treatment with TLE for 1 hr and 48 hrs. Approximately 991 genes out of the 30,000 genes in the human genome were significantly (p<0.05) changed after the treatment. Within this gene set, 88 were significantly changed between the TLE treated cells and the untreated MCF-7 cells (control cells) with a cut-off fold change >2.00. In order to focus on genes that were involved in cancer cell growth, only twenty-nine genes were selected, either down-regulated or up-regulated after treatment with TLE. Microarray assay results were confirmed by analyzing 10 of the most up and down regulated genes related to cancer cells progression using real-time PCR. Treatment with TLE induced significant up-regulation in the expression of the CRYAB, PIM1, BTG1, CYR61, HIF1-α and CEBP-β genes after 1 hr and 48 hrs, whereas the TXNIP and THBS1 genes were up-regulated after 1 hr of treatment but down-regulated after 48 hrs. In addition both the HMG1L1 and HIST2H3D genes were down-regulated after 1 hr and 48 hrs of treatment. These results demonstrate the potent activity of TLE as an anticancer agent.
    Matched MeSH terms: Breast Neoplasms/genetics
  16. Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women
    Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA
    Asian Pac J Cancer Prev, 2010;11(3):713-6.
    PMID: 21039041
    A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.
    Matched MeSH terms: Breast Neoplasms/genetics
  17. C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre
    Sharifah NA, Lee BR, Clarence-Ko CH, Tan GC, Shiran MS, Naqiyah I, et al.
    Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):663-70.
    PMID: 19271345
    Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic indicator in breast carcinoma in the local population.
    Matched MeSH terms: Breast Neoplasms/genetics*
  18. Fulltext Does a positive family history influence the presentation of breast cancer?
    Yip CH, bt Mohd Taib NA, Lau PC
    Asian Pac J Cancer Prev, 2008 Jan-Mar;9(1):63-5.
    PMID: 18439076
    INTRODUCTION: An important risk factor for developing breast cancer is a positive family history of breast cancer. In Malaysia, there is no population-based breast screening programme, but the clinical practice guidelines suggest increased surveillance for those with a positive family history ie mammography for those 40 years old and above, breast self-examination and clinical breast examination yearly.
    OBJECTIVE: To determine if women with a family history of breast cancer present with earlier stages of disease.
    METHODOLOGY: From Jan 2001 to Dec 2006, 1553 women with breast cancer presenting to the University Malaya, where family history was recorded, were eligible for this study. Women with a first or second degree relative with breast cancer were compared with those who have no family history with regard to their race, age, stage, size and duration of symptoms. The Chi Square test of significance was used for analysis.
    RESULTS: Out of 1553 patients, 252 (16.2%) were found to have a relative with breast cancer out of which 174 (11.2%) had at least one affected first degree relative. There were no significant difference in the incidence of positive family history between the Malays, Chinese and Indians. 20% below the age of 40 years old had a positive family history compared with 12.6% in women with no family history. (p<0.05). There was no significant difference in stage at diagnosis between those with and without family history, ie 24.2% late stages (Stage 3 and 4) in the group with no family history compared with 21.8% in the group with family history. (p>0.05). The mean size in the group with no family history was 4.4 cm compared to 4.1 cm in the group with family history. There was a significant difference in screen-detected cancers in the women with family history, 10.7% compared with 5.1% of screen-detected cancers in the group without a family history. However there was no difference in the duration of symptoms between the 2 groups--25.8% in the women without a family history presented after 1 year of symptoms compared with 22.4% in the group with a family history (p>0.05).
    CONCLUSION: Having a family history of breast cancer does not appear to have much impact on the health-seeking behavior of women. Even though there were more screen detected cancers, these comprised only 10% of the group with family history. Public education should target women at risk ie with family history to encourage these women to present earlier and to undergo screening for breast cancer.
    Matched MeSH terms: Breast Neoplasms/genetics*
  19. Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women
    Chong ET, Goh LP, See EU, Chuah JA, Chua KH, Lee PC
    Asian Pac J Cancer Prev, 2016;17(2):647-53.
    PMID: 26925658
    BACKGROUND: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study.

    MATERIALS AND METHODS: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

    RESULTS: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population.

    CONCLUSIONS: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.

    Matched MeSH terms: Breast Neoplasms/genetics*
  20. Overview on Epigenetic Re-programming: A Potential Therapeutic Intervention in Triple Negative Breast Cancers
    Mohamad Hanif EA, Shah SA
    Asian Pac J Cancer Prev, 2018 Dec 25;19(12):3341-3351.
    PMID: 30583339
    Breast cancer treatments leads to variable responses. Hormonal therapy is beneficial to receptor positive breast cancer
    subtypes and display better clinical outcome than triple negative breast cancers (TNBCs) with FEC (5-Fluorouracil,
    Epirubicin and Cyclophosphamide) the mainstay chemotherapy regiment. Owning to their negative expressions of
    estrogen (ER), progesterone (PR) and HER2 receptors, disease recurrence and metastasis befalls some patients indicating
    resistance to FEC. Involvement of epigenetic silencing through DNA methylation, histone methylation, acetylation and
    sumoylation may be the key player in FEC chemoresistance. Epigenetic and molecular profiling successfully classified
    breast cancer subtypes, indicating potential driver mechanisms to the progression of TNBCs but functional mechanisms
    behind chemoresistance of these molecular markers are not well defined. Several epigenetic inhibitors and drugs have
    been used in the management of cancers but these attempts are mainly beneficial in hematopoietic cancers and not
    specifically favourable in solid tumours. Hypothetically, upon administration of epigenetic drugs, recovery of tumour
    suppressor genes is expected. However, high tendency of switching on global metastatic genes is predicted. Polycomb
    repressive complex (PRC) such as EZH2, SETD1A, DNMT, is known to have repressive effects in gene regulation and
    shown to inhibit cell proliferation and invasion in breast cancers. Individual epigenetic regulators may be an option
    to improve chemo-drug delivery in cancers. This review discussed on molecular signatures of various breast cancer
    subtypes and on-going attempts in understanding underlying molecular mechanisms of epigenetic regulators as well
    as providing insights on possible ways to utilize epigenetic enzymes/inhibitors with responses to chemotherapeutic
    drugs to re-program cellular and biological outcome in TNBCs.
    Matched MeSH terms: Triple Negative Breast Neoplasms/genetics*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links