Ava Kwong

Hong Kong Sanatorium & Hospital, Hong Kong, Hong Kong

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Publications (121)582.31 Total impact

  • Valentina Silvestri · Daniel Barrowdale · Anna Marie Mulligan · Susan L. Neuhausen · Stephen Fox · Beth Y. Karlan · Gillian Mitchell · Paul James · Darcy L. Thull · Kristin K. Zorn · [...] · Saundra S. Buys · Mary B. Daly · Anita Bane · Mary Beth Terry · Esther M. John · Melissa Southey · Douglas F. Easton · Georgia Chenevix-Trench · Antonis C. Antoniou · Laura Ottini ·

    No preview · Article · Dec 2016 · Breast cancer research: BCR
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    ABSTRACT: Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses.
    Full-text · Article · Feb 2016
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    ABSTRACT: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer patients have higher metastatic rate than patients with other breast cancer subtypes. Distant metastasis is one of the causes leading to the high mortality rates. Cyclooxygenase-2 (COX2) is associated with breast cancer metastasis and the downstream prostaglandin E2 (PGE2) exerted its effect through EP receptors (EP1-EP4). However, the exact molecular events of EP receptors in breast cancer metastasis remain undefined. Expressions of EP receptors were determined during cancer development in NOD-SCID mice inoculated with MB-231 and MB-231-EP2 clone. EP2 overexpressing stable clone was constructed to investigate the proliferation and invasion potentials in vivo and in vitro. Drug transporter array was used to identify EP2 receptor-associated drug transported genes in breast cancer metastasis. Localization of EP2 receptor in primary tissues and xenografts were examined by immunostaining. Stable EP2-expression cells formed larger tumors than parental cells in mice model and was highly expressed in both primary and metastatic tissues. Silencing of EP2 receptor by siRNA and antagonist (AH 6809) significantly decreased cell proliferation and invasion, concomitant with reduced MMP-2 and MMP-9 expressions. Results from array data showed that expression of SLC19A3 was markedly increased in EP2 siRNA transfected cells. Ectopic expression of SLC19A3 retarded cell proliferation, invasion and MMPs expressions. Notably, SLC19A3 had a lower expression in primary tissues and was negatively correlated with EP2 receptor expression. Our novel finding revealed that EP2 receptor regulated metastasis through downregulation of SLC19A3. Thus, targeting EP2-SLC19A3 signaling is a potential therapeutic therapy for treating metastatic breast cancer.
    No preview · Article · Jan 2016 · American Journal of Cancer Research
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    Full-text · Dataset · Jan 2016
  • J. W. Y. Chiu · R. Leung · V. Tang · I. Cheuk · J. Lo · H. Wong · G. Kwok · D. Suen · T. Yau · A. Kwong

    No preview · Conference Paper · Dec 2015
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    ABSTRACT: Despite the declining incidence of gastric cancer, mortality rate remains high due to late presentation. We aimed to evaluate the sensitivity of miRNA as a diagnostic marker for gastric cancer in the circulation. Plasma samples from 3 independent groups comprise 123 gastric cancer patients and 111 healthy controls for miRNA profiling from microarray screening. Microarray data showed that 25 miRNAs were upregulated in gastric cancer patients and 6 highly expressed miRNAs (miR-18a, miR-140-5p, miR-199a-3p, miR-627, miR-629 and miR-652) were selected for validation. In an independent validation set, levels of miR-627, miR-629 and miR-652 were significantly higher in gastric cancer patients than healthy controls (P <0.0001). An algorithm with improved sensitivity and specificity as gastric cancer classifier was adopted and validated in another random set of 15 plasma samples. Results showed that combination of 3 miRNAs obtained the highest area under curve, with a cut-off at 0.373, with a sensitivity of 86.7 % and a specificity of 85.5 %. This study revealed a three-miRNA signature as a promising classifier for gastric cancer, and greatly enhances the feasibility of circulating miRNAs as non-invasive diagnostic marker for this disease.
    Preview · Article · Dec 2015 · Molecular Cancer
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    ABSTRACT: Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.
    No preview · Article · Nov 2015 · Journal of the National Cancer Institute
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    ABSTRACT: Background: BRCA1/BRCA2 mutations are associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Compared with the Western developed countries, genetic testing and risk assessment for HBOC in Asia are less available, thus prohibiting the appropriate surveillance, clinical strategies and cancer management. Methods: The current status of HBOC management in 14 Asian countries, including genetic counselling/testing uptakes and clinical management options, was reviewed. We analysed how economic factors, healthcare and legal frameworks, and cultural issues affect the genetic service availability in Asia. Results: In 2012, only an estimated 4,000 breast cancer cases from 14 Asian countries have benefited from genetic services. Genetic testing costs and the absence of their adoption into national healthcare systems are the main economic barriers for approaching genetic services. Training programmes, regional accredited laboratories and healthcare professionals are not readily available in most of the studied countries. A lack of legal frameworks against genetic discrimination and a lack of public awareness of cancer risk assessment also provide challenges to HBOC management in Asia. Conclusions: The Asian BRCA Consortium reports the current disparities in genetic services for HBOC in Asia and urges the policy makers, healthcare sectors and researchers to address the limitations in HBOC management.
    No preview · Article · Nov 2015 · Public Health Genomics
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    ABSTRACT: Background: Compared with male surgeons, women have less success advancing their careers and are underrepresented in leadership positions in surgery. The purpose of this study is to identify the qualifications necessary to become leaders in surgery and the career barriers faced by women surgeons in various cultural environments. Methods: A survey was performed with women surgeons in Japan, USA, Finland, and Hong Kong, China, to assess various barriers faced by women surgeons in the respective countries. To develop appropriate survey tool, a preliminary questionnaire was distributed to leaders in surgery and also in various organizations worldwide. Results: The response rate was 23 % with 225 of 964 survey returned. Japanese women surgeons identify lacked family support as impeding a successful surgical career. US women surgeons feel more latent gender discrimination. Finnish women surgeons are less likely to need to sacrifice work-life balance, when holding leadership positions. Women surgeons worldwide are highly motivated to develop their career and agree the percentage of women surgeons in leadership positions should be increased. Conclusions: Women surgeons in different countries perceive different challenges. We must develop strategies and should not hesitate to negotiate to overcome these issues to reach leadership positions in surgery. This may be accomplished through networking worldwide to improve current conditions and obstacles.
    No preview · Article · Nov 2015 · World Journal of Surgery
  • Xin Liu · Ava Kwong · Alan Sihoe · Kent-Man Chu
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    ABSTRACT: It was reported that circulating microRNAs could be applied as non-invasive biomarkers for cancer monitoring. The purpose of this study was to identify plasma miRNA that may serve as a novel biomarker for gastric cancer and to evaluate its clinical application. MicroRNA profiles were generated from plasma samples of 5 patients with gastric cancer (GC) versus 5 healthy controls (HC). MicroRNA-940 (miR-940) was one of the most downregulated miRNAs with fold change of 0.164. It was revealed that the expression of miR-940 was downregulated in both the initial set (N = 30, P < 0.0001) and the validation set (N = 80, P < 0.0001) of plasma samples of patients with gastric cancer. The sensitivity was obviously higher than the current biomarkers CEA and CA19-9 (81.25 % vs. 22.54 % and 15.71 %). MiR-940 was also significantly downregulated in gastric cancer tissue samples (N = 34, P = 0.0015), as well as in cancer cell lines (N = 7). Importantly, miR-940 was significantly highly expressed in stomach tissue samples than in other types of tissue samples including the liver, breast, thyroid, and lung. Moreover, there was a trend of lower expression of miR-940 from early to advanced stage of gastric cancer. Target prediction suggested that miR-940 regulated cell signaling including NF-κB and Wnt/β-catenin, as well as pathways of cell communication and adhesion. These pathways play critical roles in gastric cancer initiation and progression. It is the first report that miR-940 may mainly express in the stomach. Downregulation of plasma miR-940 may serve as a novel biomarker for detection of gastric cancer.
    No preview · Article · Oct 2015 · Tumor Biology
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    ABSTRACT: Background Mammographic density (MD) is a strong intermediate risk factor for breast cancer (BC) and, having both genetic and environmental determinants, may account for the over 6-fold international variations in BC incidence rates. The International Pooling Project of Mammographic Density is a worldwide collaborative project of MD targeting populations spanning the BC incidence range. The aims of the project are to (i) describe international variations in overall and age-specific distributions of MD, (ii) assess whether international variations in MD are explained by variations in the distributions of individual-level determinants of this marker and (iii) examine whether international variations in MD correlate with corresponding BC incidence rates. Methods Each contributing study provided comparable data on MD risk factors and mammographic images from a random sample of ˜ 400 general population women, who had undergone screening mammography. Images were transferred in digitised screen-film, full-field or computed radiography digital DICOM format (raw or processed). Images were randomly allocated into batches for MD reading using the Cumulus 6 thresholding software, by experienced readers who were blinded to study and individual-level factors. Data on MD determinants were pooled and linked with MD readings. Results are calibrated according to type of digital image (raw to processed), and adjusted for image type. Results 22 countries and approximately 12,000 women are included, spanning populations with age-standardised BC incidence rates (ASR) of 25.8 (India) to 99 (The Netherlands) per 100,000 woman-years. To date, for 9,635 participants data have been pooled (results will be updated). The MD risk factors vary greatly across populations, for example: mean age at menarche (in years) was 14.3 (95% CI 14.1–14.5) in Korean women and 12.6 (12.5–12.8) in Mexican women; mean parity was 3.8 (3.6–4.1) in Egyptian women and 1.3 (1.1–1.4) in those from Hong Kong; and mean BMI (in kg/m2) was 33.7 (33.1–34.3) in Egyptian women compared to 22.3 (21.6–22.9) in those from India. Differences in MD according to these distributions will be presented. Discussion The international perspective of this study generated large exposure heterogeneity enabling a wider investigation of MD determinants and the extent to which MD is an intermediate marker of BC risk, both within and between populations.
    Full-text · Article · Sep 2015 · Journal of Epidemiology & Community Health
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    ABSTRACT: Rapid advances of next-generation sequencing technology have led to the integration of genetic information with clinical care. Genetic basis of diseases and response to drugs provide new ways of disease diagnosis and safer drug usage. This integration reveals the urgent need for effective and accurate tools to analyze genetic variants. Due to the number and diversity of sources for annotation, automating variant analysis is a challenging task. Here, we present database.bio, a web application that combines variant annotation, prioritization and visualization so as to support insight into the individual genetic characteristics. It enhances annotation speed by preprocessing data on a supercomputer, and reduces database space via a unified database representation with compressed fields. Availability and implementation: Freely available at https://database.bio Contact: rb{at}l3-bioinfo.com or twlam{at}cs.hku.hk Supplementary information: Supplementary data are available at Bioinformatics online.
    Full-text · Article · Aug 2015 · Bioinformatics

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: Brain metastasis occurs in 10-15% of metastatic breast cancer patients and is associated with poor prognosis. This study aims to identify tumor characteristics of primary breast cancer, which are related to brain metastases in Hong Kong Chinese patients. A retrospective study of patients with invasive breast cancer receiving treatment in a university hospital from January 2001 to December 2008 was performed. The clinicopathological factors of patients with brain metastases were analyzed and compared with those who had no brain metastasis. Risk factors for brain metastasis were identified by univariate analysis first and then by multivariate analysis. A total of 912 patients with invasive breast cancer were treated during the study period. Of these, 30 patients were found to have distant metastases to brain. Patients with brain metastases had more breast tumors of higher histological grade (Grade III, 78.9% vs. 30.2%; p = 0.001). Their tumors also had a significantly higher rate of negative estrogen receptors (78.9% vs. 30.2%, p = 0.001). On multivariate analysis, only high tumor grading was found to be predictive of developing brain metastasis. Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients. Copyright © 2015. Published by Elsevier Taiwan.
    No preview · Article · Jul 2015
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    ABSTRACT: Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. In this review, we compiled data from 11 participating Asian countries (Bangladesh, Mainland China, Hong Kong SAR, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Thailand and Vietnam), and from ethnic Asians residing in Canada and the USA. We have additionally conducted a literature review to include other Asian countries mainly in Central and Western Asia. We present the current pathogenic mutation spectrum of BRCA1/BRCA2 genes in patients with breast cancer in various Asian populations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · Jul 2015 · Journal of Medical Genetics
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    ABSTRACT: A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment. One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives. High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect. Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Jun 2015 · Psycho-Oncology
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    ABSTRACT: Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer. Sanger sequencing has been the gold standard in identifying these mutations. However, 4-28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing) and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified 120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and LGRs could be detected. We suggest that MLPA should be incorporated into the standard practice for genetic testing to avoid false-negative results, which would greatly affect the management of these high-risk families. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Cancer Genetics
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    ABSTRACT: The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006- 2011 in five Asian centers (N=1138) were included. Survival between patients receiving mastectomy only, breast conserving therapy (BCT, lumpectomy and adjuvant radiotherapy), and mastectomy with radiotherapy were compared, and adjusted for demography, tumor characteristics, and chemotherapy types. Median age at diagnosis was 53 years (range: 23-96 years). Median tumor size at diagnosis was 2.5 cm and most patients had lymph node negative disease. The majority of patients received adjuvant chemotherapy (n=861, 76%) comprising predominantly anthracycline-based regimes. In 775 women with T1-2,N0-1,M0 TNBCs, 5-year relative survival ratio (RSR) was highest in patients undergoing mastectomy only (94.7%, 95%CI: 88.8%-98.8%), followed by BCT (90.8%, 95%CI: 85.0%-94.7%), and mastectomy with radiotherapy (82.3%, 95%CI: 73.4%-88.1%). The adjusted risks of mortality between the three groups were not significantly different. In 363 patients with T3-4,N2-3,M0 TNBCs, BCT was associated with highest 5-year RSR (94.1%, 95%CI: 81.3%-99.4%), followed by mastectomy with radiotherapy (62.7%, 95%CI: 54.3%-70.1%), and mastectomy only (58.6%, 95%CI: 43.5%-71.6%). Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy seems to be independently associated with a survival gain in locally advanced, as well as in very young TNBC. This article is protected by copyright. All rights reserved. © 2015 UICC.
    No preview · Article · May 2015 · International Journal of Cancer

  • No preview · Article · May 2015 · Cancer Research

  • No preview · Article · May 2015 · Cancer Research

Publication Stats

939 Citations
582.31 Total Impact Points

Institutions

  • 2011-2015
    • Hong Kong Sanatorium & Hospital
      Hong Kong, Hong Kong
    • Hong Kong Hospital Authority
      Hong Kong, Hong Kong
  • 2008-2015
    • The University of Hong Kong
      • Department of Surgery
      Hong Kong, Hong Kong
  • 2007-2015
    • Queen Mary Hospital
      Hong Kong, Hong Kong
    • Stanford University
      • • Department of Surgery
      • • Department of Medicine
      • • Department of Radiology
      Stanford, California, United States
  • 2014
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 2013
    • University of Otago
      Taieri, Otago, New Zealand
  • 2012
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom