Displaying publications 161 - 180 of 1168 in total

Abstract:
Sort:
  1. Ng T, Toh MR, Cheung YT, Chan A
    Support Care Cancer, 2015 Nov;23(11):3193-200.
    PMID: 25791392 DOI: 10.1007/s00520-015-2700-2
    PURPOSE: The aim of this study is to evaluate the perspectives of Asian oncology practitioners on the physical and psychosocial issues experienced by breast cancer survivors (BCS), current survivorship care practices, and the barriers to follow-up care.

    METHODS: This was a cross-sectional survey study. Oncology practitioners were recruited from a major cancer center in Singapore and through two regional cancer meetings that took place in Singapore and Malaysia in 2013.

    RESULTS: A total of 126 oncology practitioners from various Southeast Asian countries, mostly nurses (58.7 %) and physicians (37.3 %), were recruited. The majority of the respondents agreed that fatigue (78.4 %) and anxiety (69.1 %) were the most common physical and psychosocial problems experienced by BCS. Monitoring for physical and treatment-related adverse effects (80.7 %) and reviewing patients' noncancer medical history (65.3 %) were the most practiced aspects of follow-up care. Compared with the other practitioners, the physicians were more likely to communicate with other healthcare professionals (adjusted OR = 4.24, 95 % CI 1.54 to 11.72; p = 0.005). Most of the respondents also agreed that patient-specific barriers were the main impediments to follow-up care.

    CONCLUSION: This study provides insights into the various aspects of breast cancer survivorship care from the perspectives of oncology practitioners and shows that survivorship care is relatively inadequate in Asia. There is a need for new survivorship care models to meet the needs of Asian BCS and to complement the unique healthcare systems of Asia.

    Matched MeSH terms: Breast Neoplasms/psychology*; Breast Neoplasms/therapy
  2. Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, et al.
    Future Oncol, 2019 Jul;15(21):2489-2501.
    PMID: 31140297 DOI: 10.2217/fon-2019-0143
    Aim: To evaluate the efficacy and safety of neratinib as extended adjuvant therapy in patients from Asia based on exploratory analyses of the Phase III ExteNET trial. Patients & methods: A total of 2840 women with early stage HER2-positive breast cancer were randomly assigned to neratinib 240 mg/day or placebo for 1 year after trastuzumab-based adjuvant therapy. Results: A total of 341 patients were from Asia (neratinib, n = 165; placebo, n = 176). 2-year invasive disease-free survival rates were 92.8 and 90.8% with neratinib and placebo, respectively (HR: 0.70; 95% CI: 0.31-1.55), and 5-year rates were 91.9 and 87.2%, respectively (HR: 0.57; 95% CI: 0.27-1.13). Diarrhea was the most common adverse event with neratinib. Conclusion: Extended adjuvant therapy with neratinib reduces disease recurrences in Asian women with HER2-positive breast cancer. Trial registration: Clinicaltrials.gov NCT00878709.
    Matched MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/metabolism*; Breast Neoplasms/pathology
  3. Ang JY, Bhojwani K, Chan HK, Chan AC
    Acupunct Med, 2021 02;39(1):64-68.
    PMID: 32539426 DOI: 10.1177/0964528420920307
    INTRODUCTION: The objective of this retrospective study was to evaluate the effectiveness and safety of acupuncture-assisted anesthesia (AAA) in breast lump excision.

    METHODS: The medical records of all patients who underwent breast lump excision under AAA in combination with electrical stimulation at traditional acupuncture points in 2016 were examined. All of them (n = 17) received electrostimulation (2-4 Hz) using single needles inserted at bilateral LI4 and PC6. They also underwent insertion of four acupuncture needles at the lump site, which were electrically stimulated at 30 Hz frequency.

    RESULTS: All surgical procedures were successful with minimal use of analgesics and local anesthetic. The median pain score reported was 1/10 (interquartile range (IQR) = 2/10) at the first hour, and slightly increased to 2/10 (IQR = 2/10) between 24 and 48 h of the surgery. No major postoperative adverse events were documented, except for drowsiness in one case.

    CONCLUSION: AAA was found to be generally safe and effective for anaesthesia and analgesia in breast lump excision. However, a large-scale randomized controlled study is required to verify the findings.

    Matched MeSH terms: Breast Neoplasms/surgery*
  4. Chan KE
    Med J Malaysia, 1982 Sep;37(3):217-20.
    PMID: 7177001
    In a 10 year period 1971-1980, the records of 944 individual women with benign breast lumps and 228 with primary carcinomata are reviewed. This study describes the age, ethnic distribution of benign and malignant breast tumours in women in Peninsular Malaysia and compares the pattern with Western experience. There are important variations in the incidence pattern between the different races in Peninsular Malaysia and between them and women in Britain and the United States.
    Matched MeSH terms: Breast Neoplasms/epidemiology*
  5. Alhabshi SM, Rahmat K, Abu Hassan H, Westerhout CJ, Chandran PA
    Jpn J Radiol, 2013 May;31(5):342-8.
    PMID: 23385379 DOI: 10.1007/s11604-013-0183-y
    Phyllodes tumour or cystosarcoma phyllodes is a rare stromal breast tumour that is usually benign but on rare occasions can turn malignant. Non-specificity of the imaging features on sonography and mammography makes it difficult to distinguish malignant from benign counterparts solely based on imaging. The final diagnosis is still highly dependent on histopathological assessment. Herein, we describe two cases of malignant phyllodes tumour with emphasis on magnetic resonance (MR) imaging features using advanced MR applications.
    Matched MeSH terms: Breast Neoplasms/pathology*
  6. Lee JJ, Saiful Yazan L, Che Abdullah CA
    Int J Nanomedicine, 2017;12:2373-2384.
    PMID: 28392694 DOI: 10.2147/IJN.S127329
    Breast cancer is the most common malignancy worldwide, especially among women, with substantial after-treatment effects. The survival rates of breast cancer have decreased over the years even with the existence of various therapeutic strategies, specifically, chemotherapy. Clinical drugs administered for breast cancer appear to be non-targeting to specific cancer sites leading to severe side effects and potentially harming healthy cells instead of just killing cancer cells. This leads to the need for designing a targeted drug delivery system. Nanomaterials, both organic and inorganic, are potential drug nanocarriers with the ability of targeting, imaging and tracking. Various types of nanomaterials have been actively researched together with their drug conjugate. In this review, we focus on selected nanomaterials, namely solid-lipid, liposomal, polymeric, magnetic nanoparticles, quantum dots, and carbon nanotubes and their drug conjugates, for breast cancer studies. Their advantages, disadvantages and previously conducted studies were highlighted.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  7. Wan Mohd Shukri WN, Bakhtiar H, Islam S, Bidin N, Baba S, Hamdan S, et al.
    Biomed Environ Sci, 2021 Feb 20;34(2):119-123.
    PMID: 33685570 DOI: 10.3967/bes2021.017
    Matched MeSH terms: Breast Neoplasms/therapy*
  8. Rahmah, M.A., Aniza, I., Che Engku Nor Bahiyah, C.E.M.
    MyJurnal
    Despite the debates of the benefits of continuing mammography screening among elderly women, studies in Malaysia have shown that the prevalence of breast examination declines after age 45 years and for mammogram per se, the prevalence of examination increases until age of 64. This study aims to determine the prevalence of mammogram screening among elderly women in Hulu Langat, Selangor and its relationship with factors such as demographic factors, family history of breast cancer, perceived health status, perceived general psychological factor and lifestyle factors. Data used were from a cross sectional study of health status among community in Hulu Langat area by the Department of Community Health, Universiti Kebangsaan Malaysia carried out from the year 1998 till 2002. However this paper focused on the database involving elderly women age 60 and above. The sample population was 652. The mean (standard deviation) age was 67.17 (5.995). Only 8.3% of the elderly women claimed to ever had mammogram screening done. Hence, the prevalence of mammogram screening is still low among elderly women in Hulu Langat. Having family history of breast cancer (p < 0.001) and perceived positive psychological status (p=0.003) had shown significant associations with mammogram screening among them. It is therefore important for researcher to further look into the reasons behind this and qualitative exploration is highly recommended.
    Matched MeSH terms: Breast Neoplasms
  9. Mohd Nafi SN, Siti Azrin AH, Mat Zin AA, Othman NH, Che Jalil NA
    Malays J Pathol, 2019 Apr;41(1):33-39.
    PMID: 31025635
    INTRODUCTION: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM).

    MATERIALS AND METHODS: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient's demographic and clinicopathological data.

    RESULTS: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers.

    CONCLUSIONS: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.

    Matched MeSH terms: Breast Neoplasms
  10. Looi LM, Cheah PL
    Malays J Pathol, 1998 Jun;20(1):19-23.
    PMID: 10879259
    Eighty-six infiltrating ductal carcinoma of breast were studied by the standard avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2 oncoprotein expression. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. 21% tumours were ER positive while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2 positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while 25% of c-erbB-2 negative tumours were ER positive. This negative relationship between ER and c-erbB-2 expression was statistically significant (Mc Nemar's test, p < 0.005). The ER positivity rate did not vary significantly with histological grade. However, c-erbB-2 overexpression was significantly more prevalent in grade III tumours compared with grade I and II tumours (Chi-square test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be expected to relate to more aggressive tumour proliferation and may explain its correlation with high histological grade, a known indicator of aggressive cancer behaviour. As there is no indication that ER protein activity contributes to advancement in histological grade, it would appear that cellular dedifferentiation precedes ER loss during malignant transformation. It has been mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein overexpression have a poorer response to hormonal therapy. The use of this parameter in the routine assessment of breast cancer patients may identify subsets of patients for more aggressive therapy.
    Matched MeSH terms: Breast Neoplasms/metabolism*; Breast Neoplasms/pathology
  11. Looi LM, Yap SF, Cheah PL
    Ann Acad Med Singap, 1997 Nov;26(6):750-3.
    PMID: 9522973
    Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.
    Matched MeSH terms: Breast Neoplasms/chemistry*
  12. Hamid SS, Cheah SH
    Hybridoma (Larchmt), 2011 Apr;30(2):137-43.
    PMID: 21529286 DOI: 10.1089/hyb.2010.0091
    Breast mucin is secreted by breast tumor cells and serves as a marker for breast cancer. Thus, antibodies against breast mucin will be valuable in the development of immunotherapy and laboratory diagnostic tests. Monoclonal antibodies (MAbs) against breast cancer-associated antigen were generated and characterized. Balb/c mice were immunized with breast cancer-associated antigen CA15-3, and subsequently splenocytes from immunized mice were fused with myeloma cells. After fusion, culture supernatants from hybridomas surviving HAT medium were screened by enzyme-linked immunosorbent assay (ELISA). A total of eight hybridomas producing MAbs against breast cancer showed significant levels of antibody activity against CA15-3. Two selected stable hybridomas were adapted into CELLine CL 350 bioreactors, and the MAbs produced were characterized for their subclass, specificity, and affinity. The MAbs were of high specificity and affinity as shown by ELISA. The MAbs produced may represent a powerful tool and are considered promising reagents for use in diagnosis and detection of early stage of the disease.
    Matched MeSH terms: Breast Neoplasms/diagnosis; Breast Neoplasms/immunology*; Breast Neoplasms/pathology
  13. Zain NM, Chelliah KK
    Asian Pac J Cancer Prev, 2014;15(3):1327-31.
    PMID: 24606460
    BACKGROUND: Electrical impedance tomography (EIT) is a new non-invasive, mobile screening method which does not use ionizing radiation to the human breast; allows conducting quantitative assessment of the images besides the visual interpretation. The aim of this study was to correlate the quantitative assessment and visual interpretation of breast electrical impedance tomographs and associated factors.

    MATERIALS AND METHODS: One hundred and fifty mammography patients above 40 years and undergoing EIT were chosen using convenient sampling. Visual interpretation of the images was carried out by a radiologist with minimum of three years experience using the breast imaging - electrical impedance (BI-EIM) classification for detection of abnormalities. A set of thirty blinded EIT images were reinterpreted to determine the intra-rater reliability using kappa. Quantitative assessment was by comparison of the breast average electric conductivity with the norm and correlations with visual interpretation of the images were determined using Chi-square. One-way ANOVA was used to compare the mean electrical conductivity between groups and t-test was used for comparisons with pre-existing Caucasians statistics. Independent t-tests were applied to compare the mean electrical conductivity of women with factors like exogenous hormone use and family history of breast cancer.

    RESULTS: The mean electrical conductivity of Malaysian women was significantly lower than that of Caucasians (p<0.05). Quantitative assessment of electrical impedance tomography was significantly related with visual interpretation of images of the breast (p<0.05).

    CONCLUSIONS: Quantitative assessment of electrical impedance tomography images was significantly related with visual interpretation.

    Matched MeSH terms: Breast Neoplasms/prevention & control
  14. Voon NS, Chelliah KK
    Asian Pac J Cancer Prev, 2011;12(8):1969-72.
    PMID: 22292635
    The purpose of this study was to evaluate the influence of dietary habit on breast density, which is an important risk factor for breast cancer. This cross-sectional study was performed on 64 Malaysian women of all races between the age of 35 to 70 years. All subjects underwent mammography and the breast density was analyzed from the images using BI-RADS by two independent radiologists. A validated food-frequency questionnaire was used to evaluate the nutrient intake. The data were analyzed using Chi-square test to evaluate the association of dietary habits to breast density. Based on the results, mutton, pork, vegetables, sweets, snacks, soy bean and eggs intake showed associations with increased breast density (p < 0.05) while grains, meat, beverages, oil and fruits, did not show any association (p > 0.05). As a conclusion, this study showed diet may make changes to the breast density as a risk factor for breast cancer.
    Matched MeSH terms: Breast Neoplasms/etiology*
  15. Zain NM, Seriramulu VP, Chelliah KK
    Asian Pac J Cancer Prev, 2016;17(7):3229-34.
    PMID: 27509955
    BACKGROUND: Bone mineral density (BMD) is a lifetime marker of estrogen in a woman's body and has been associated with increased breast cancer risk. Nonetheless the actual association is still debatable. Furthermore, estrogen is very crucial in maintaining human bone density and gradually decreases over age. A systematic search was conducted to assess any association of BMD with breast cancer risk factors among premenopausal and postmenopausal women.

    MATERIALS AND METHODS: Review identification was performed through databases searching on MEDLINE, CINAHL and SCOPUS and 19 qualified studies were elected. The keywords used were "bone mineral density", "breast cancer", and "breast density".

    RESULTS: A total of 19 articles showed variation with the majority of the studies focused on postmenopausal and a few focused on premenopausal women. Overall there was no concensus on effects.

    CONCLUSIONS: An enormous effort is being undertaken by researchers to prove that BMD might be one of the significant risk factors for breast cancer.
    Matched MeSH terms: Breast Neoplasms/etiology*; Breast Neoplasms/pathology
  16. Tew LS, Cai MT, Lo LW, Khung YL, Chen NT
    Materials (Basel), 2018 Jul 09;11(7).
    PMID: 29987236 DOI: 10.3390/ma11071170
    Photodynamic therapy (PDT) is a cancer treatment that employs the production of cytotoxic reactive oxygen species (ROS), subsequently triggering tumor apoptosis and tumor size reduction. However, this approach suffers from insufficient light penetration depth. In order to mitigate this issue, pollen-structured gold clusters (PSGCs) were designed for mediating X-ray-induced PDT for radiotherapy enhancement. The structure of PSGCs provides a large surface area that is able to generate ROS upon X-ray irradiation. The synthesized PSGCs were exposed to different X-ray doses and the generated ROS was then quantified by dihydroethidium (DHE) assay. Furthermore, at the cellular level, the PDT efficacy of PSGCs was evaluated via immunofluorescence staining with γ-H2AX and comet assay. The results demonstrated that PSGCs possess a significantly high ROS-generating capacity and a remarkable PDT efficacy in the treatment of breast cancer cells, thus showing potential clinical uses in deep-tissue cancer treatment.
    Matched MeSH terms: Breast Neoplasms
  17. Tan AA, Phang WM, Gopinath SC, Hashim OH, Kiew LV, Chen Y
    Biomed Res Int, 2015;2015:453289.
    PMID: 26167486 DOI: 10.1155/2015/453289
    Breast cancer is one of the major issues in the field of oncology, reported with a higher prevalence rate in women worldwide. In attempt to reveal the potential biomarkers for breast cancer, the findings of differentially glycosylated haptoglobin and osteonectin in previous study have drawn our attention towards glycoproteins of secretome from the MCF-7 cancer cell line. In the present study, further analyses were performed on the medium of MCF-7 cells by subjecting it to two-dimensional analyses followed by image analysis in contrast to the medium of human mammary epithelial cells (HMEpC) as a negative control. Carboxypeptidase A4 (CPA4), alpha-1-antitrypsin (AAT), haptoglobin (HP), and HSC70 were detected in the medium of MCF-7, while only CPA4 and osteonectin (ON) were detected in HMEpC medium. In addition, CPA4 was detected as upregulated in the MCF-7 medium. Further analysis by lectin showed that CPA4, AAT, HP, and HSC70 were secreted as N-glycan in the medium of MCF-7, with HP also showing differentially N-glycosylated isoforms. For the HMEpC, only CPA4 was detected as N-glycan. No O-glycan was detected in the medium of HMEpC but MCF-7 expressed O-glycosylated CPA4 and HSC70. All these revealed that glycoproteins could be used as glycan-based biomarkers for the prognosis of breast cancer.
    Matched MeSH terms: Breast Neoplasms/secretion*
  18. Guo G, Zhang W, Dang M, Yan M, Chen Z
    J Biochem Mol Toxicol, 2019 Apr;33(4):e22268.
    PMID: 30431692 DOI: 10.1002/jbt.22268
    Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in breast cancer. The major snag faced by the human population is the development of chemoresistance to HER2 inhibitors by advanced stage breast cancer cells. Moreover, recent researchers focussed on fisetin as an antiproliferative and chemotherapeutic agent. Therefore, this study was intended to analyze the effects of fisetin on HER2/neu-overexpressing breast cancer cell lines. Our results depicted that fisetin induced apoptosis of these cells by various mechanisms, such as inactivation of the receptor, induction of proteasomal degradation, decreasing its half-life, decreasing enolase phosphorylation, and alteration of phosphatidylinositol 3-kinase/Akt signaling.
    Matched MeSH terms: Breast Neoplasms/enzymology; Breast Neoplasms/metabolism; Breast Neoplasms/pathology*
  19. Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, et al.
    J Med Genet, 2016 May;53(5):298-309.
    PMID: 26921362 DOI: 10.1136/jmedgenet-2015-103529
    BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.

    METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia.

    RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75).

    CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.

    Matched MeSH terms: Breast Neoplasms/genetics; Breast Neoplasms/metabolism*; Breast Neoplasms/epidemiology
  20. 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*
Filters
Contact Us

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

External Links