Displaying publications 1 - 20 of 140 in total

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  1. Liu J, Lončar I, Collée JM, Bolla MK, Dennis J, Michailidou K, et al.
    Sci Rep, 2016 11 15;6:36874.
    PMID: 27845421 DOI: 10.1038/srep36874
    NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
  2. Lee HB, Ho AS, Teo SH
    Cancer Chemother. Pharmacol., 2006 Jul;58(1):91-8.
    PMID: 16211395
    Given that p53 is a tumor suppressor that plays a central role in the cellular response to DNA damage and that more than 50% of all cancers have mutated p53, the wider utility of photodynamic therapy (PDT) in the treatment of cancer will depend on an understanding of whether p53 status modulates response to PDT. In this study, we investigated the photosensitivity of isogenic cell lines that differ only in their p53 status to PDT using hypericin as the photosensitizer.
  3. Zulkhernain NS, Teo SH, Patel V, Tan PJ
    Curr Cancer Drug Targets, 2014;14(8):764-73.
    PMID: 25348017 DOI: 10.2174/1568009614666141028121347
    Targeted therapy, the treatment of cancer based on an underlying genetic alteration, is rapidly gaining favor as the preferred therapeutic approach. To date, although natural products represent a rich resource of bio-diverse drug candidates, only a few have been identified to be effective as targeted cancer therapies largely due to the incompatibilities to current high-throughput screening methods. In this article, we review the utility of a zebrafish developmental screen for bioactive natural product-based compounds that target signaling pathways that are intimately shared with those in humans. Any bioactive compound perturbing signaling pathways identified from phenotypic developmental defects in zebrafish embryos provide an opportunity for developing targeted therapies for human cancers. This model provides a promising tool in the search for targeted cancer therapeutics from natural products.
  4. Earp M, Tyrer JP, Winham SJ, Lin HY, Chornokur G, Dennis J, et al.
    PLoS ONE, 2018;13(7):e0197561.
    PMID: 29979793 DOI: 10.1371/journal.pone.0197561
    Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
  5. Mariapun S, Ho WK, Kang PC, Li J, Lindström S, Yip CH, et al.
    Cancer Epidemiol. Biomarkers Prev., 2016 Feb;25(2):327-33.
    PMID: 26677210 DOI: 10.1158/1055-9965.EPI-15-0746
    Mammographic density is an established risk factor for breast cancer and has a strong heritable component. Genome-wide association studies (GWAS) for mammographic density conducted in women of European descent have identified several genetic associations, but none of the studies have been tested in Asians. We sought to investigate whether these genetic loci, and loci associated with breast cancer risk and breast size, are associated with mammographic density in an Asian cohort.
  6. Gan CP, Hamid S, Hor SY, Zain RB, Ismail SM, Wan Mustafa WM, et al.
    Head Neck, 2012 Mar;34(3):344-53.
    PMID: 21438066 DOI: 10.1002/hed.21734
    There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC.
  7. Dörk T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al.
    Sci Rep, 2019 Aug 29;9(1):12524.
    PMID: 31467304 DOI: 10.1038/s41598-019-48804-y
    Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
  8. Ng CH, Ripolles TS, Hamada K, Teo SH, Lim HN, Bisquert J, et al.
    Sci Rep, 2018 02 06;8(1):2482.
    PMID: 29410450 DOI: 10.1038/s41598-018-20228-0
    Perovskite solar cells based on series of inorganic cesium lead bromide and iodide mixture, CsPbBr3-xI x , where x varies between 0, 0.1, 0.2, and 0.3 molar ratio were synthesized by two step-sequential deposition at ambient condition to design the variations of wide band gap light absorbers. A device with high overall photoconversion efficiency of 3.98 % was obtained when small amount of iodide (CsPbBr2.9I0.1) was used as the perovskite and spiro-OMeTAD as the hole transport material (HTM). We investigated the origin of variation in open circuit voltage, Voc which was shown to be mainly dependent on two factors, which are the band gap of the perovskite and the work function of the HTM. An increment in Voc was observed for the device with larger perovskite band gap, while keeping the electron and hole extraction contacts the same. Besides, the usage of bilayer P3HT/MoO3 with deeper HOMO level as HTM instead of spiro-OMeTAD, thus increased the Voc from 1.16 V to 1.3 V for CsPbBr3 solar cell, although the photocurrent is lowered due to charge extraction issues. The stability studies confirmed that the addition of small amount of iodide into the CsPbBr3 is necessarily to stabilize the cell performance over time.
  9. Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, et al.
    Oral Oncol., 2010 May;46(5):379-86.
    PMID: 20371203 DOI: 10.1016/j.oraloncology.2010.02.022
    Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.
  10. Teo Sh, Teh K, Azura L, Ng Y
    Malays Orthop J, 2011 Nov;5(3):32-4.
    PMID: 25279034 MyJurnal DOI: 10.5704/MOJ.1111.005
    Tuberculosis (TB), once a disease confined to undeveloped or developing nations is currently in resurgence due to pandemic human immunodeficiency virus infection and immigration from endemic areas. TB is also known as the 'great mimicker'. Extra-pulmonary tuberculosis affecting the knee is rare in all forms of TB (0.1-0.3%). Here, we report a case of isolated highly erosive TB knee in a previously fit Burmese migrant worker. He presented with after a history of fall into a drain. The patient also reported pain and swelling over his left knee for the previous three years. He had been treated for a bacterial infection of the knee in another hospital but defaulted due to financial constraints. Arthrotomy of the knee was performed including washout. Diagnosis of TB of the knee was made based on the synovial fluid and tissue culture. Treatment with antituberculosis drugs was then initiated.
  11. Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al.
    Mol Genet Genomic Med, 2019 Jun;7(6):e707.
    PMID: 31066241 DOI: 10.1002/mgg3.707
    BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.

    METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.

    RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).

    CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

  12. Abdullah A, Abdullah KL, Yip CH, Teo SH, Taib NA, Ng CJ
    Asian Pac. J. Cancer Prev., 2013;14(12):7143-7.
    PMID: 24460266
    BACKGROUND: The survival outcomes for women presenting with early breast cancer are influenced by treatment decisions. In Malaysia, survival outcome is generally poor due to late presentation. Of those who present early, many refuse treatment for complementary therapy.
    OBJECTIVE: This study aimed to explore the decision making experiences of women with early breast cancer.
    MATERIALS AND METHODS: A qualitative study using individual in-depth interviews was conducted to capture the decision making process of women with early breast cancer in Malaysia. We used purposive sampling to recruit women yet to undergo surgical treatment. A total of eight participants consented and were interviewed using a semi-structured interview guide. These women were recruited from a period of one week after they were informed of their diagnoses. A topic guide, based on the Ottawa decision support framework (ODSF), was used to facilitate the interviews, which were audio recorded, transcribed and analysed using a thematic approach.
    RESULTS: We identified four phases in the decision-making process of women with early breast cancer: discovery (pre-diagnosis); confirmatory ('receiving bad news'); deliberation; and decision (making a decision). These phases ranged from when women first discovered abnormalities in their breasts to them making final surgical treatment decisions. Information was vital in guiding these women. Support from family members, friends, healthcare professionals as well as survivors also has an influencing role. However, the final say on treatment decision was from themselves.
    CONCLUSIONS: The treatment decision for women with early breast cancer in Malaysia is a result of information they gather on their decision making journey. This journey starts with diagnosis. The women's spouses, friends, family members and healthcare professionals play different roles as information providers and supporters at different stages of treatment decisions. However, the final treatment decision is influenced mainly by women's own experiences, knowledge and understanding.
    Study site: Breast surgical units, Klang Valley, Malaysia
  13. Colombo M, Lòpez-Perolio I, Meeks HD, Caleca L, Parsons MT, Li H, et al.
    Hum. Mutat., 2018 05;39(5):729-741.
    PMID: 29460995 DOI: 10.1002/humu.23411
    Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10-115 . There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.
  14. Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, et al.
    Eur. Urol., 2014 Sep;66(3):489-99.
    PMID: 24484606 DOI: 10.1016/j.eururo.2014.01.003
    BACKGROUND: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations.

    OBJECTIVE: To report the first year's screening results for all men at enrollment in the study.

    DESIGN, SETTING AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types.

    RESULTS AND LIMITATIONS: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups.

    CONCLUSIONS: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease.

    PATIENT SUMMARY: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.

  15. Ong CY, Ling SK, Ali RM, Chee CF, Samah ZA, Ho AS, et al.
    J. Photochem. Photobiol. B, Biol., 2009 Sep 4;96(3):216-22.
    PMID: 19647445 DOI: 10.1016/j.jphotobiol.2009.06.009
    One hundred and fifty-five extracts from 93 terrestrial species of plants in Peninsula Malaysia were screened for in vitro photo-cytotoxic activity by means of a cell viability test using a human leukaemia cell-line HL60. These plants which can be classified into 43 plant families are diverse in their type of vegetation and their natural habitat in the wild, and may therefore harbour equally diverse metabolites with potential pharmaceutical properties. Of these, 29 plants, namely three from each of the Clusiaceae, Leguminosae, Rutaceae and Verbenaceae families, two from the Piperaceae family and the remaining 15 are from Acanthaceae, Apocynaceae, Bignoniaceae, Celastraceae, Chrysobalanaceae, Irvingiaceae, Lauraceae, Lythraceae, Malvaceae, Meliaceae, Moraceae, Myristicaceae, Myrsinaceae, Olacaceae and Sapindaceae. Hibiscus cannabinus (Malvaceae), Ficus deltoidea (Moraceae), Maranthes corymbosa (Chrysobalanaceae), Micromelum sp., Micromelum minutum and Citrus hystrix (Rutaceae), Cryptocarya griffithiana (Lauraceae), Litchi chinensis (Sapindaceae), Scorodocarpus bornensis (Olacaceae), Kokoona reflexa (Celastraceae), Irvingia malayana (Irvingiaceae), Knema curtisii (Myristicaceae), Dysoxylum sericeum (Meliaceae), Garcinia atroviridis, Garcinia mangostana and Calophyllum inophyllum (Clusiaceae), Ervatamia hirta (Apocynaceae), Cassia alata, Entada phaseoloides and Leucaena leucocephala (Leguminosae), Oroxylum indicum (Bignoniaceae), Peronema canescens,Vitex pubescens and Premna odorata (Verbenaceae), Piper mucronatum and Piper sp. (Piperaceae), Ardisia crenata (Myrsinaceae), Lawsonia inermis (Lythraceae), Strobilanthes sp. (Acanthaceae) were able to reduce the in vitro cell viability by more than 50% when exposed to 9.6J/cm(2) of a broad spectrum light when tested at a concentration of 20 microg/mL. Six of these active extracts were further fractionated and bio-assayed to yield four photosensitisers, all of which are based on the pheophorbide-a and -b core structures. Our results suggest that the main photosensitisers from terrestrial plants are likely based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in minor amounts or are not as active as those with the cyclic tetrapyrrole structure.
  16. Lee YS, Teo SH, Ahn JH, Lee OS, Lee SH, Lee JH
    Arthroscopy, 2017 Oct;33(10):1884-1895.
    PMID: 28655477 DOI: 10.1016/j.arthro.2017.04.006
    PURPOSE: To evaluate the surgical treatment of the discoid lateral meniscus (DLM) with long-term follow-up and to search which factors are related to good clinical or radiological outcomes.

    METHODS: Search was performed using a MEDLINE, EMBASE, and Cochrane database, and each of the selected studies was evaluated for methodological quality using a risk of bias (ROB) covering 7 criteria. Clinical and radiological outcomes with more than 5 years of follow-up were evaluated after surgical treatment of DLM. They were analyzed according to the age, follow-up period, kind of surgery, DLM type, and alignment.

    RESULTS: Eleven articles (422 DLM cases) were included in the final analysis. Among 7 criteria, 3 criteria showed little ROB in all studies. However, 4 criteria showed some ROB ("Yes" in 63.6% to 81.8%). The minimal follow-up period was 5.5 years (weighted mean follow-up: 9.1 years). Surgical procedures were performed with open or arthroscopic partial central meniscectomy, subtotal meniscectomy, total meniscectomy, or partial meniscectomy with repair. The majority of the studies showed good clinical results. Mild joint space narrowing was reported in the lateral compartment, but none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy could be related to degenerative change. The majority of the complications was osteochondritis dissecans at the lateral femoral condyle (13 cases) and reoperation was performed by osteochondritis dissecans (4 cases), recurrent swelling (2 cases), residual symptom (1 case), stiffness (1 case), and popliteal stenosis (1 case).

    CONCLUSIONS: Good clinical results were obtained with surgical treatment of symptomatic DLM. The progression of degenerative change was minimal and none of the knees demonstrated moderate or advanced degenerative changes. Increased age at surgery, longer follow-up period, and subtotal or total meniscectomy were possible risk factors for degenerative changes.

    LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

  17. Song CV, Teo SH, Taib NA, Yip CH
    Ecancermedicalscience, 2018;12:863.
    PMID: 30174725 DOI: 10.3332/ecancer.2018.863
    Introduction: The presence of a deleterious mutation, most commonly a BRCA mutation, has a tremendous impact on the management of breast cancer. We review the surgical management of BRCA mutation carriers, and two other potentially high-risk mutations, TP53 and PALB2.

    Methodology: A search was done on PubMed, limited to reviews and the English language only. The search terms used were 'BRCA' or 'PALB2' or 'TP53' and 'surgery'. Fifteen articles were identified by searching and one article was obtained from other sources.

    Results: Breast-conserving surgery has equivalent survival, but may have an increased risk of local recurrence, compared to mastectomy among BRCA mutation carriers. Contralateral prophylactic mastectomy may not improve overall survival, despite reducing the risk of developing contralateral breast cancer. The use of preoperative genetic testing allows patients to have combined curative and prophylactic surgery. However, preoperative genetic testing may influence patients to make rash decisions. In healthy BRCA mutation carriers, bilateral prophylactic mastectomy is done to prevent breast cancer from occurring. Bilateral prophylactic mastectomy is highly effective in reducing the risk of breast cancer in healthy BRCA mutation-positive women and may have a survival benefit. Prophylactic oophorectomy reduces the risk of ovarian cancer, but may not have an effect on the risk of breast cancer. There is a lack of studies on surgery for non-BRCA mutations. TP53 and PALB2 are potentially high-risk mutations for breast cancer, which may justify the use of prophylactic surgery. Advice should be given on a case-by-case basis.

    Conclusion: A comprehensive approach is needed to provide optimum treatment for breast cancer patients with deleterious mutations.

  18. Islam A, Teo SH, Rahman MA, Taufiq-Yap YH
    PLoS ONE, 2015;10(12):e0144805.
    PMID: 26700479 DOI: 10.1371/journal.pone.0144805
    A solution-phase route has been considered as the most promising route to synthesize noble nanostructures. A majority of their synthesis approaches of calcium carbonate (CaCO3) are based on either using fungi or the CO2 bubbling methods. Here, we approached the preparation of nano-precipitated calcium carbonate single crystal from salmacis sphaeroides in the presence of zwitterionic or cationic biosurfactants without external source of CO2. The calcium carbonate crystals were rhombohedron structure and regularly shaped with side dimension ranging from 33-41 nm. The high degree of morphological control of CaCO3 nanocrystals suggested that surfactants are capable of strongly interacting with the CaCO3 surface and control the nucleation and growth direction of calcium carbonate nanocrystals. Finally, the mechanism of formation of nanocrystals in light of proposed routes was also discussed.
  19. Brouckaert O, Rudolph A, Laenen A, Keeman R, Bolla MK, Wang Q, et al.
    Breast Cancer Res., 2017 Nov 07;19(1):119.
    PMID: 29116004 DOI: 10.1186/s13058-017-0909-3
    BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.

    METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.

    RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p 

  20. Kang PC, Phuah SY, Sivanandan K, Kang IN, Thirthagiri E, Liu JJ, et al.
    Breast Cancer Res. Treat., 2014 Apr;144(3):635-42.
    PMID: 24578176 DOI: 10.1007/s10549-014-2894-x
    Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.
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