Abstract:
BACKGROUND:Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of B100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. METHODS:Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. RESULTS:Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. CONCLUSIONS:MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Saunders EJ,Dadaev T,Leongamornlert DA,Al Olama AA,Benlloch S,Giles GG,Wiklund F,Gronberg H,Haiman CA,Schleutker J,Nordestgaard BG,Travis RC,Neal D,Pasayan N,Khaw KT,Stanford JL,Blot WJ,Thibodeau SN,Maier C,Kibel ASdoi
10.1038/bjc.2016.50subject
Has Abstractpub_date
2016-04-12 00:00:00pages
945-52issue
8eissn
0007-0920issn
1532-1827pii
bjc201650journal_volume
114pub_type
杂志文章abstract::The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutatio...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1054/bjoc.2001.2128
更新日期:2001-12-14 00:00:00
abstract::The vaso-active drug hydralazine causes a considerable increase in the cytotoxic effect of melphalan towards the KHT tumour in mice. The enhancement in response, measured as the concentration of melphalan required to achieve a given tumour response, is 3.0 and 2.35 when determined using the regrowth delay assay and th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.177
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND:Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605336
更新日期:2009-11-03 00:00:00
abstract::During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.270
更新日期:1986-12-01 00:00:00
abstract::Temozolomide, an imidazotetrazine derivative, was given to 18 patients with low-grade non-Hodgkin's lymphoma (NHL) at a dose of 750 mg m-2 orally, divided over five consecutive days, escalated to 1000 mg m-2 over 5 days (i.e. 200 mg m-2 day-1) if no significant myelosuppression was noted at day 22 of the 28 day cycle....
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1995.299
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND:Current international guidelines recommend the use of platinum-based chemotherapy with thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS:Patients with unresectable stage IIIA or IIIB NSCLC were treated with nedaplatin (NP) at 50 mg m(-2) and irinoteca...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605875
更新日期:2010-10-26 00:00:00
abstract:BACKGROUND:Cisplatin-radiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). However, the cisplatin-attributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1-XPF nu...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2013.576
更新日期:2013-10-15 00:00:00
abstract::Limb-sparing surgeries have been performed more frequently than amputation based on the belief that limb-sparing surgeries provide improved function and quality-of-life (QOL). However, this has not been extensively studied in the paediatric population, which has unique characteristics that have implications for functi...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6602220
更新日期:2004-11-29 00:00:00
abstract::Recent evidence has demonstrated that endothelial-to-mesenchymal transition (EndMT) may have a significant role in a number of diseases. Although EndMT has been previously studied as a critical process in heart development, it is now clear that EndMT can also occur postnatally in various pathologic settings, including...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6604662
更新日期:2008-11-04 00:00:00
abstract::Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suita...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604463
更新日期:2008-07-22 00:00:00
abstract:BACKGROUND:Upregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients. METHODS:We assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease. RESULTS:A high protein e...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.80
更新日期:2012-04-24 00:00:00
abstract::Mechanisms of resistance to Tomudex include increased thymidylate synthase activity, as well as reduced intracellular drug uptake and polyglutamation. However, little is known about other mechanisms of resistance, such as a possible protection against Tomudex-induced apoptosis mediated by bcl-2. We transfected the MDA...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690685
更新日期:1999-09-01 00:00:00
abstract::Functionally active telomerase is affected at various steps including transcriptional and post-transcriptional levels of major telomerase components (hTR and human telomerase reverse transcriptase (hTERT)). We therefore developed a rapid and sensitive method to quantify hTERT and its splicing variants as well as the h...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602546
更新日期:2005-05-23 00:00:00
abstract::Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There...
journal_title:British journal of cancer
pub_type:
doi:10.1038/sj.bjc.6602821
更新日期:2005-10-31 00:00:00
abstract::High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragme...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.449
更新日期:1996-09-01 00:00:00
abstract::ApoE single nucleotide polymorphisms (SNPs) Cys112Arg (Epsilon-4), and Arg158Cys (Epsilon-2) have been implicated in cardiovascular and Alzheimer's disease, but their role in colorectal cancer (CRC) has not been extensively studied. We investigated whether ApoE polymorphisms alone or in combination with dietary factor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605097
更新日期:2009-06-16 00:00:00
abstract:BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) has poor survival and treatment options. PDAC cells shift their metabolism towards glycolysis, which fuels the plasma membrane calcium pump (PMCA), thereby preventing Ca2+-dependent cell death. The ATP-generating pyruvate kinase-M2 (PKM2) is oncogenic and overexpressed...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0675-3
更新日期:2020-01-01 00:00:00
abstract::Pancreatic cancer is the fifth most common cause of cancer death. Identification of defined patient groups based on a prognostic index may improve the prediction of survival and selection of therapy. Many prognostic factors have been identified often based on retrospective, underpowered studies with unclear analyses. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604568
更新日期:2008-09-16 00:00:00
abstract::Using flow cytometry and immunocytochemistry, we investigated the reactivities of two different murine monoclonal antibodies (MAbs), MRK 16 and MRK 20, specific to adriamycin-resistant K562 cells (K562/ADM) with peripheral human mononuclear cells (MNC) (mainly blastic cells and lymphocytes) from 31 patients with leuka...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.309
更新日期:1989-10-01 00:00:00
abstract::Cellular DNA was analysed by flow cytometry in fine needles aspirates (FNA) from both benign and malignant breast lesions in order to determine the feasibility of flow cytometric analysis. In 22 of 26 (84%) benign and 69 of 74 (93%) malignant aspirates, sufficient cells were present to produce good quality DNA histogr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.259
更新日期:1987-11-01 00:00:00
abstract::This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chem...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1054/bjoc.2001.1902
更新日期:2001-07-20 00:00:00
abstract::We have evaluated the relation between cancer of the lower urinary tract ("bladder cancer") and the use of artificial sweeteners, by means of case-control studies in Manchester, U.K., and Nagoya, Japan, areas where extensive use occurred 30-40 years ago. In each area, a broadly based series of cases (555 in Manchester...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1982.59
更新日期:1982-03-01 00:00:00
abstract::Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cance...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690056
更新日期:1999-01-01 00:00:00
abstract::In a prospective study we determined the frequency and causes of delay in the diagnosis of breast cancer after suspicious screening mammography. We included all women aged 50-75 years who underwent biennial screening mammography in the southern breast cancer screening region of the Netherlands between 1 January 1996 a...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602158
更新日期:2004-11-15 00:00:00
abstract::To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpressi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.171
更新日期:1995-04-01 00:00:00
abstract:BACKGROUND:The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours det...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.27
更新日期:2012-02-28 00:00:00
abstract:BACKGROUND:Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. METHODS:All residents of Ontario diagnosed with one of the top 10 malignanci...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0390-0
更新日期:2019-04-01 00:00:00
abstract::Acquired drug resistance is a major problem in cancer treatment. To explore the genes involved in chemosensitivity and resistance, 10 human tumour cell lines, including parental cells and resistant subtypes selected for resistance against doxorubicin, melphalan, teniposide and vincristine, were profiled for mRNA expre...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602699
更新日期:2005-08-22 00:00:00
abstract::A representative sample of 4657 adults greater than or equal to 45 years of age from the 5 main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos and Hawaiians) were interviewed during 1977-1979 regarding their diets. Quantitative food-consumption histories were obtained, from which average daily intak...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.189
更新日期:1981-09-01 00:00:00
abstract:BACKGROUND:Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after ant...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.564
更新日期:2013-10-29 00:00:00