Abstract：
PURPOSE:PARP4 has been proposed as a candidate breast cancer susceptibility gene. However, its function and involvement in breast carcinogenesis is unclear. We sought to determine the variant frequency of PARP4 in BRCA-negative women referred for genetic testing from Singapore and to perform functional analyses of PARP4. METHODS:Next-generation sequencing of PARP4 was conducted for 198 BRCA-negative cases from Singapore. Three independent case-control association analyses of PARP4 were performed for (1) our Singaporean cohort, (2) three dbGaP datasets, and (3) cases from TCGA, with controls from the Exome Aggregation Consortium (ExAC). PARP4 knockout cells were generated utilizing the CRISPR-Cas9 approach in MDA-MB-231 (breast cancer) and MCF10A (normal breast) cell lines, and colony formation, cell proliferation, and migration assays carried out. RESULTS:Candidate variants in PARP4 were identified in 5.5% (11/198) of our Singapore cohort. Case-control association studies for our cases and the dbGaP datasets showed no significant association. However, a significant association was observed for PARP4 variants when comparing 988 breast cancer cases from the TCGA provisional data and 53,105 controls from ExAC (ALL) (OR 0.249, 95% CI 0.139-0.414, P = 2.86 × 10-11). PARP4 knockout did not affect the clonogenicity, proliferation rate, and migration of normal breast cells, but appeared to decrease the proliferation rate and clonogenicity of breast cancer cells. CONCLUSIONS:Taken together, our results do not support that PARP4 functions as a cancer susceptibility gene. This study highlights the importance of performing functional analyses for candidate cancer predisposition genes.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Prawira A,Munusamy P,Yuan J,Chan CHT,Koh GL,Shuen TWH,Hu J,Yap YS,Tan MH,Ang P,Lee ASGdoi
10.1007/s10549-019-05286-wsubject
Has Abstractpub_date
2019-08-01 00:00:00pages
145-153issue
1eissn
0167-6806issn
1573-7217pii
10.1007/s10549-019-05286-wjournal_volume
177pub_type
杂志文章abstract：:Published data on the association between Xeroderma Pigmentosum complementation group D (XPD) Lys751Gln polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association be...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,meta分析
doi：10.1007/s10549-010-0813-3
更新日期：2010-11-01 00:00:00
abstract：:Conflicting opinions exist concerning clinical and pathological presentation, as well as evolution and prognosis, of breast cancer in young women. The roles of associated pregnancy and lactation on these parameters is also unclear. These two conditions are studied in the present work through the comparison of two brea...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF02235745
更新日期：1985-01-01 00:00:00
abstract：:We calculated hazard rates for recurrence in patients with primary breast cancer (stage I, II; no adjuvant therapy). Previous publications have indicated a peak in hazard rates for recurrence (or death) at approximately 2-3 years after diagnosis of primary breast cancer. However, there have been conflicting reports co...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-004-1722-0
更新日期：2005-01-01 00:00:00
abstract：:Review of comparative pathology studies of breast cancer among Japanese women and other ethnic groups reveals consistent differences in tumor morphology and host response. Japanese women show lower rates of breast cancer than Caucasian women, a difference that is accounted for by increased rates of this cancer in post...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/BF02633531
更新日期：1991-05-01 00:00:00
abstract：BACKGROUND:We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor 'dimensions' were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying g...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-05097-5
更新日期：2019-05-01 00:00:00
abstract：PURPOSE:Platelets are essential components of hemostasis and also play an important role in the tumor microenvironment. The purposes of our research were to examine the role of thrombocytosis in inflammatory breast cancer (IBC) and to know which cytokine drives thrombocytosis. METHODS:We reviewed the medical records o...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4463-6
更新日期：2017-12-01 00:00:00
abstract：PURPOSE:Nearly half of the 3.5 million female breast cancer survivors in the US are aged 65 years or older at diagnosis, yet little is known about associations of obesity and physical activity with breast cancer-specific mortality (BCSM) among older survivors. METHODS:Between 1992 and 2013, 5254 women in the Cancer Pr...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4470-7
更新日期：2018-01-01 00:00:00
abstract：:Breast cancer is the most common cancer in women worldwide, accounting for just over 1 million new cases annually. Population-based statistics show that globally, when compared to whites, women of African ancestry (AA) tend to have more aggressive breast cancers that present more frequently as estrogen receptor negati...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/s10549-010-0827-x
更新日期：2010-06-01 00:00:00
abstract：:Although a wealth of research has focused on the influence of diet on breast cancer risk, the relationships between dietary factors and tumor characteristics of breast cancer, like estrogen receptor (ER) status, are not well characterized. In a case-case study, we evaluated self-reported dietary intake for five indivi...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1016588629495
更新日期：2002-09-01 00:00:00
abstract：:Although the psychosocial concomitants of early-stage breast cancer have been well-documented, the relationship between cancer recurrence and quality of life remains less clear. We conducted a prospective, longitudinal study in order to clarify the relationship between recurrent cancer and quality of life, and to dete...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1006172024218
更新日期：1999-03-01 00:00:00
abstract：:Currently, there are no applied molecular markers to aid in predicting risk of carcinoma in situ (CIS) progression to invasive cancer, and therefore, all women diagnosed with CIS undergo surgery. Standard assessment of protein expression in fixed tissue by immunohistochemistry (IHC) is not quantitative and hence is no...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-010-1227-y
更新日期：2011-09-01 00:00:00
abstract：:This study describes the inhibitory effect of 5 alpha-dihydrotestosterone (5 alpha-DHT) and its precursors testosterone (T) and androst-4-ene-3,17-dione (delta 4-DIONE) on the growth of the estrogen-sensitive human breast cancer cell line ZR-75-1. In the absence of estrogens, cell proliferation measured after a 12-day...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01805942
更新日期：1988-10-01 00:00:00
abstract：:We have compared by RNA in situ hybridisation on serial cryo-sections the distribution of cathepsin D (cathD), stromelysin 3 (strom-3), and urokinase plasminogen activator (UPA) gene expression in different tissues of human benign and malignant mammary tumors. Cath-D expression was found to be higher in adenocarcinoma...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01806676
更新日期：1996-01-01 00:00:00
abstract：PURPOSE:The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several brea...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4502-3
更新日期：2018-01-01 00:00:00
abstract：:Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK)...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-010-0857-4
更新日期：2011-02-01 00:00:00
abstract：PURPOSE:To investigate the activity of the combination of gemcitabine (G) plus epirubicin (E) and taxol (T), (GET), in metastatic breast cancer, to evaluate the feasibility of this regimen as induction before high dose chemotherapy and to study the pharmacokinetic interactions of these three drugs. PATIENTS AND METHOD...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章
doi：10.1023/a:1011945623464
更新日期：2001-07-01 00:00:00
abstract：:HER2/neu overexpression leads to poorer prognosis and higher risk of disease reoccurrence in breast cancer patients. The causative factors responsible for increasing HER2/neu expression levels on mammary cells are not known. We investigated whether factors associated with inflammation or metastasis could induce HER2/n...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-012-2191-5
更新日期：2012-09-01 00:00:00
abstract：PURPOSE:Little is known about racial variations in the financial impact of cancer care. Using data from a national survey of racially diverse patients with metastatic breast cancer, we examined racial/ethnic patterns in employment and cost-management (i.e., financial coping) behaviors. METHODS:We conducted an online s...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-019-05449-9
更新日期：2020-01-01 00:00:00
abstract：:Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II, randomized, open-label study comparing fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. At data cut-off, only 36 % of patients had pro...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s10549-012-2192-4
更新日期：2012-11-01 00:00:00
abstract：PURPOSE:It has been suggested that type 2 diabetes may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The purpose of this study was to examine the impact of diabetes on survival following breast cancer. METHODS:Us...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9654-0
更新日期：2008-05-01 00:00:00
abstract：:The relation between estrogen receptors (ER) in breast cancer and risk factors was studied in 456 Japanese patients. ER was shown to be positive in 55.3% (252/456) of patients. There was no difference in ER positivity between pre- and postmenopausal patients. In premenopausal patients, only the age at menarche and obe...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01806986
更新日期：1984-01-01 00:00:00
abstract：:Germline mutations in BRCA1/2 increase the lifetime risk for breast and ovarian cancer dramatically. Identification of such mutations is important for optimal treatment decisions and pre-symptomatic mutation screening in family members. Although current DNA diagnostics is able to identify many different mutations, it ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-010-1016-7
更新日期：2012-04-01 00:00:00
abstract：:Analysis of germline p53 mutations in breast cancer reveals that the Li-Fraumeni and Li-Fraumeni-like syndromes are mostly related to the loss of initiation codon 133 of regulatory TP53 isoforms (Delta133p53). In eight codons of exons 5-8 (including 133), mutations are frequent in Li-Fraumeni-related, but scarce in sp...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9514-y
更新日期：2007-12-01 00:00:00
abstract：OBJECTIVE:To examine the content, quality and reliability of YouTube videos related to breast self-examination. DESIGN:A search of YouTube was made on 21.06.2018 using the keyword of "breast self-examination". The videos were categorised by two doctors as useful information or misleading information. To evaluate the q...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-5044-z
更新日期：2019-02-01 00:00:00
abstract：PURPOSE:The Janus-associated kinase (JAK)/signal transducer and activator of transcription pathway is a key regulator of inflammatory signaling, associated with tumorigenesis, cell survival, and progression. This randomized phase 2 trial evaluated the efficacy and safety of the addition of ruxolitinib, a JAK1/JAK2 inhi...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10549-018-4770-6
更新日期：2018-08-01 00:00:00
abstract：:BRCA1 protein is normally expressed in the nuclei of breast epithelial cells and functions as a negative regulator of the cell cycle. Mutations of BRCA1 gene have been associated with familial breast carcinomas. Although somatic mutations have not been demonstrated in sporadic breast carcinomas, loss of nuclear expres...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1013317909431
更新日期：2002-01-01 00:00:00
abstract：:Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer. Observational epidemiologic data also provide some support for inverse associations with risk. We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferati...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1007/s10549-008-0213-0
更新日期：2009-07-01 00:00:00
abstract：:Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altere...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-013-2671-2
更新日期：2013-08-01 00:00:00
abstract：:Based on our previous findings that medroxyprogesterone acetate (MPA) significantly suppressed the formation of preneoplastic mammary hyperplastic alveolar nodules in mice, and that this suppression persisted for some time, we studied the effects of different schedules of MPA treatment on spontaneous mammary tumorigen...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01805741
更新日期：1988-09-01 00:00:00
abstract：PURPOSE:Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and associated with early metastasis, drug resistance, and poor patient survival. Fork head box M1 (FOXM1) is considered as an emerging molecular target due to its oncogenic role and high overexpression profile in 85% in TNBC. However, ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-017-4207-7
更新日期：2017-06-01 00:00:00
