Abstract:
:A subset of aggressive colorectal cancers exhibit BRAF mutation, MLH1 methylation, and a CpG island methylator phenotype (CIMP), but precursors are poorly established. In this study, we determined the status of these markers in colorectal polyps and evaluated associated risk factors. The study included 771 polyp cases and 1,027 controls who were ages 24 to 80 years, part of a group health program, received a colonoscopy from 1998 to 2007, and completed a structured questionnaire assessing risk factors. Following standard pathology review, polyps were assayed for BRAF mutation (V600E) and tested for MLH1 and CIMP methylation, the latter including the genes, CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1. Polytomous logistic regression was used to estimate ORs and 95% confidence intervals for the association between molecularly defined subsets of polyps and potential risk factors. There were 580 conventional adenomas and 419 serrated lesions successfully assayed. For adenomas, the prevalence of each marker was ≤1%. In contrast, 55% of serrated lesions harbored mutant BRAF, 26% were CIMP-high, and 5% had methylated MLH1. In these lesions, the highest prevalence of markers was in sessile-serrated polyps (SSP) of ≥10 mm that were in the right-side/cecal regions of the colon. Risk factors for CIMP-high-serrated lesions included Caucasian race, current smoking status, and a history of polyps, whereas for serrated lesions with mutant BRAF, the significant risk factors were male sex, current smoking status, obesity, and a history of polyps. Our results suggest that SSPs and other large, right-sided serrated lesions have a unique molecular profile that is similar to CIMP-high, BRAF-mutated colorectal cancers.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Burnett-Hartman AN,Newcomb PA,Potter JD,Passarelli MN,Phipps AI,Wurscher MA,Grady WM,Zhu LC,Upton MP,Makar KWdoi
10.1158/0008-5472.CAN-12-3462subject
Has Abstractpub_date
2013-05-01 00:00:00pages
2863-72issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-3462journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::A high-affinity localization of [2H]methylcholanthrene and/or its metabolites to a specific nuclear fraction (Fraction l) between 4 and 72 hr of exposure is described. Other carcinogenic hydrocarbons, such as benzo(a)pyrene and dibenz(a,h)anthracene, demonstrate a similar markded localization in Fraction l after 24 hr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This tot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-15 00:00:00
abstract::Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cel...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4350
更新日期:2007-05-01 00:00:00
abstract::Virion antigens of feline leukemia virus are associated with HLA antigens in the membrane of human cells infected with the virus. Feline leukemia virus produced by these cells incorporates host membrane antigens into the virion envelope, making the virus susceptible to lysis by antisera directed to HLA or to uninfecte...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract::Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2864
更新日期:2008-03-01 00:00:00
abstract::The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mammary tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::Epidemiologic studies have reported the underrepresentation of cervical precancerous lesions caused by human papillomavirus (HPV) types 18 and 45 (HPV18/45) compared with the proportion of cervical cancers attributed to these HPV types. We investigated the timing of diagnosis of histologic cervical intraepithelial neo...
journal_title:Cancer research
pub_type: 杂志文章,随机对照试验
doi:10.1158/0008-5472.CAN-08-4192
更新日期:2009-04-15 00:00:00
abstract::p51/p63 is a novel p53 homologue that has been shown to act as a transcriptional activator through the p53-binding sequence of the p21/WAF1 promoter and to induce apoptosis when it is expressed transiently in a human tumor cell line. We developed transcription assay systems for these two related genes in both Saccharo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-06-15 00:00:00
abstract::Multiple tobacco smoke-related premalignant and malignant lesions develop synchronously or metachronously in various organ sites, including the oral cavity. Both field cancerization and clonal migration seem to contribute to the occurrence of multiple tumors. Although the importance of endogenous factors (e.g., oncoge...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1388
更新日期:2007-09-15 00:00:00
abstract::Multimodal therapy is generally more effective than single-agent treatment for cancer. rRp450 is an engineered herpes simplex viral mutant that replicates in and kills tumor cells in a relatively selective fashion. It also expresses, in infected cells, the cyclophosphamide (CPA)-sensitive rat cytochrome P450 2B1 (CYP2...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-08-15 00:00:00
abstract::Tumor-associated mutants of the p53 tumor suppressor protein exert biological activities compatible with an oncogenic gain of function. To explore the underlying molecular mechanism, we performed microarray analysis, comparing p53-null cells to mutant p53-expressing cells. One of the genes up-regulated in the presence...
journal_title:Cancer research
pub_type: 杂志文章,收录出版
doi:10.1158/0008-5472.CAN-04-1145
更新日期:2004-11-15 00:00:00
abstract::S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was shown to provide marked protection against development of radiation-induced leg contractures in C3Hf/Kam mice whose legs were exposed to single doses of gamma-radiation. The radiation doses ranged from 3300 to 6200 rads delivered to the right hind thighs ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract::The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1008
更新日期:2010-08-01 00:00:00
abstract::The efficiency of tumor induction by oncogenes is influenced by modifier genes that determine individual susceptibility. We have used a transgenic mouse model to examine the role of a candidate susceptibility gene, bcl-2, for development of Raf oncogene-induced lung adenomas. Loss of bcl-2 greatly retarded tumor devel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::Breast cancer is a heterogeneous disease with distinct molecular subtypes characterized by differential response to targeted and chemotherapeutic agents. Enhanced understanding of the genetic alterations characteristic of different subtypes is needed to pave the way for more personalized administration of therapeutic ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0234
更新日期:2008-07-01 00:00:00
abstract::Tumor-specific rosette-forming cells reactive to solubilized tumor antigens conjugated to autologous erythrocytes were quantitated by flow cytofluorometry. Leukocytes from a high frequency of the patients (greater than 70%) with squamous cell carcinoma of the head and neck (SQCC) formed rosettes to the conjugated SQCC...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::We observed that photodynamic therapy (PDT) induces the expression and phosphorylation of the inhibitor of apoptosis (IAP) protein survivin in murine and human cancer cells and tumors. Survivin inhibits caspase-9, blocks apoptosis, and is associated with resistance to chemotherapy and radiation. Survivin is a client p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4785
更新日期:2007-05-15 00:00:00
abstract::PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3132
更新日期:2012-04-01 00:00:00
abstract::Transforming growth factor beta (TGF-beta) is a potent growth-regulatory and immunomodulatory cytokine that exerts a diverse range of effects on many types of cells. High levels of TGF-beta are produced by several human and mouse malignant mesothelioma (MM) cell lines, and it is known to act as a growth factor for the...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Mice lacking N-acetylglucosaminyltransferase III (GlcNAc-TIII) exhibit slightly but significantly retarded liver tumor progression after a single injection of 10 micro g/g diethylnitrosamine (DEN) and continued administration of phenobarbital (PB) in drinking water. A key question is whether the absence of GlcNAc-TIII...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-11-15 00:00:00
abstract::We have previously described an MCF-7 breast cancer cell variant, MCF-7TAM, which is stimulated to grow in athymic mice by tamoxifen (TAM) (M. M. Gottardis and V. C. Jordan, Cancer Res., 48:5183-5187, 1988). Earlier experiments have shown that TAM exhibits some profound estrogen-like effects in mice whereas TAM is les...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Several properties of four 1-deaza-7,8-dihydropteridines were compared with those of each other and with those of colchicine, nocodazole, podophyllotoxin, and vincristine. Compound NSC 370147 was more active than the other compounds of this type with respect to inhibition of proliferation of cultured L1210 cells and t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-03-15 00:00:00
abstract::Heteroantisera were produced in rabbits by immunization with cultivated cells from rat intestinal carcinomas. The sera were made specific by in vivo absorption in syngeneic rats. On immunofluorescence, these sera recognized a membrane-associated antigen common to five different intestinal carcinomas and to fetal intes...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-02-01 00:00:00
abstract::The effect of pretreatment with L-asparaginase on the cytotoxicity of methotrexate (MTX) was studied in L5178Y murine leukemic cells and L-929 cells grown in vitro. The results were correlated with the effects of L-asparaginase on DNA synthesis. At low concentrations of the enzyme, pretreatment of cells enhanced the e...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-06-01 00:00:00
abstract::Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impact...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-1231
更新日期:2020-11-15 00:00:00
abstract::Studies of V79-171 cells were undertaken to determine what extracellular or intracellular derivative of the drug WR-2721 is associated with radioprotection. The effect of preincubation at 23 +/- 1 degree C with WR-2721, and with derivatives of WR-2721 produced in medium containing alkaline phosphatase, upon survival o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::HL60 cells, human promyelocytic leukemia cells, can be induced to differentiate into more mature myeloid forms by dimethyl sulfoxide (DMSO) or retinoic acid (RA) and into macrophage-like cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) or related compounds. Macrophage differentiation of HL60 cells by TPA treatment ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::The possibility of decreasing the gastrointestinal (GI) toxic effects of 5-fluorouracil (5-FU) on the digestive tract such as its injury of cells and induction of diarrhea, without reducing its antitumor activity, was investigated in rats. Oxonic acid was found to inhibit the phosphorylation of 5-FU to 5-fluorouridine...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::The purpose of this study was to investigate the immunobiological characteristics of the tumor-specific cell surface antigen expressed by the UV-induced murine fibrosarcoma, UV-2240. UV-2240 is classified as a regressor UV tumor because it is immunologically rejected by normal syngeneic mice but grows in immunocomprom...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-12-15 00:00:00
abstract::Whole-slide histology images contain information that is valuable for clinical and basic science investigations of cancer, but extracting quantitative measurements from these images is challenging for researchers who are not image analysis specialists. In this paper, we describe HistomicsML2, a software tool for learn...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-0668
更新日期:2020-12-21 00:00:00