Abstract:
:Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤ 55. We found that carriers of the rs16430 0 bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR) = 1.37, 95% confidence interval (CI): 1.08-1.73; P = 0.010], compared with carriers of the 6 bp/6 bp genotype. This increased risk was more evident in older subjects (OR = 1.47, 95% CI = 1.06-2.03, P = 0.022), never smokers (OR = 1.67, 95% CI = 1.23-2.25, P < 0.001), never drinkers (OR = 1.44, 95% CI = 1.01-2.05, P = 0.043), and estrogen receptor-positive patients (OR = 1.46, 95% CI = 1.11-1.92, P = 0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0 bp allele had a decrease in both luciferase activity by ∼ 70% and mRNA levels by ∼ 50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561. Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤ 55 yr. Further validation in large population-based or cohort studies is needed.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Guan X,Liu H,Ju J,Li Y,Li P,Wang LE,Brewster AM,Buchholz TA,Arun BK,Wei Q,Liu Zdoi
10.1002/mc.22097subject
Has Abstractpub_date
2015-04-01 00:00:00pages
281-90issue
4eissn
0899-1987issn
1098-2744journal_volume
54pub_type
杂志文章abstract::Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin-2 receptor (IL-2R) induces tumorigenic transformation, constitutively active IL-2R in tumors has not been reported. We searched for genomic alteration of the IL-2/15R beta-subunit gene (IL-2/15R beta) in cytokine-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10128
更新日期:2003-06-01 00:00:00
abstract::The extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK) pathway is an important cell proliferation pathway. We previously reported that the transport protein particle complex 4 (TRAPPC4), ERK2 interaction may activate ERK1/2, modulate pERK2 nuclear localization and regulate proliferati...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22031
更新日期:2014-02-01 00:00:00
abstract::Notch signaling plays an important role in ovarian cancer chemoresistance, which is responsible for recurrence. Gamma-secretase inhibitor (GSI) is a broad-spectrum Notch inhibitor, but it has serious side effects. The efficacy of Notch3-specific inhibition in paclitaxel-resistant ovarian cancers was assessed in this s...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22363
更新日期:2016-07-01 00:00:00
abstract::Increasing evidence from recent research suggests a connection between cancer and a deranged equilibrium of histone acetylation, which is maintained by two competing enzymatic activities, histone acetyltransferases (HATs) and histone deacetylases (HDACs). It is our hypothesis that a significant proportion of leukemias...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(200004)27:4<268::aid-mc4>3
更新日期:2000-04-01 00:00:00
abstract::Dishevelled-3 (Dvl-3) and p120-catenin (p120ctn) have abnormal expression in non-small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl-3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl-3 cDNA to NSCLC cells. Dvl-3 transfection i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22196
更新日期:2015-06-01 00:00:00
abstract::The mouse benign keratinocyte cell line 308 was previously shown to have less AP-1 DNA binding and transactivation ability than its malignant variant 10Gy5. Because elevated AP-1 activity in 10Gy5 appears to be critical for its malignant phenotype, we were interested in examining the molecular mechanisms that regulate...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199701)18:1<26::aid-mc4>3.
更新日期:1997-01-01 00:00:00
abstract::Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20764
更新日期:2011-08-01 00:00:00
abstract::Using relatively primitive tools in the 1920s, Otto Warburg demonstrated that tumor cells show an increased dependence on glycolysis to meet their energy needs, regardless of whether they were well-oxygenated or not. High rates of glucose uptake, fueling glycolysis, are now used clinically to identify cancer cells. Ho...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.21863
更新日期:2013-05-01 00:00:00
abstract::Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rode...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22164
更新日期:2015-09-01 00:00:00
abstract::Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the associatio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20495
更新日期:2009-06-01 00:00:00
abstract::Bone cells are a prime target for the biological function of the fos/jun (activating protein-1 (AP-1)) transcription factor complex. Deregulated expression of c-fos or v-fos in bone cells induces tumorigenicity and the formation of non-metastatic osteosarcomas. In contrast, fos oncogenes transform fibroblasts to an in...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::The restriction of energy intake has a profound inhibitory effect on carcinogenesis, yet the mechanism or mechanisms that account for this effect are unknown. In this experiment, the hypothesis tested was that energy restriction upregulates the expression of p27/kip1, a gene product associated with cell-cycle growth a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199904)24:4<241::aid-mc1>3
更新日期:1999-04-01 00:00:00
abstract::The ubiquitin-proteasome pathway is fundamental to synchronized continuation of many cellular processes, for example, cell-cycle progression, stress response, and cell differentiation. Recent studies have shown that the ubiquitin-proteasome pathway functions in the regulation of nucleotide excision repair (NER) in yea...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20065
更新日期:2005-01-01 00:00:00
abstract::RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20598
更新日期:2010-03-01 00:00:00
abstract::Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Se...
journal_title:Molecular carcinogenesis
pub_type: 临床试验,杂志文章
doi:10.1002/mc.21868
更新日期:2012-10-01 00:00:00
abstract::The majority of ovarian cancers over-express the estrogen receptor (ERα) and grow in response to estrogens. We previously demonstrated that ER induction of the chemokine CXCL12 (stromal cell-derived factor-1) is required for estradiol (E2)-stimulated proliferation of human ovarian carcinoma cells. In the current study...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21913
更新日期:2013-09-01 00:00:00
abstract::We found that caffeine significantly inhibited epidermal growth factor (EGF)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in the JB6 mouse epidermal cell line. The tumor promoter-induced cell transformation was also blocked by treatment with an adenosine A1 receptor antagonist, 8-phenylt...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20120
更新日期:2005-09-01 00:00:00
abstract::Here, we have demonstrated that xenobiotic activation of the nuclear receptor (CAR, NR1I3) can result in arresting DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase. Huh7 cells over-expressing CAR were either treated with dimethyl sulfoxide, the CAR activator TCPOBOP (1,4-bis[2-(3,5-dichloropyrid...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20783
更新日期:2012-02-01 00:00:00
abstract::Metformin, an oral biguanide for the treatment of type II diabetes, has been shown to have anticancer effects in ovarian cancer. Energy starvation induced by metformin causes endoplasmic reticulum stress-mediated unfolded protein response (UPR) and autophagy. UPR and autophagy act as a survival or death mechanism in c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22284
更新日期:2016-04-01 00:00:00
abstract::Carcinogenesis is a multistep sequential process of clonal expansion of initiated cells associated with the accumulation of multiple cancer-specific heritable phenotypes. The acquisition of these heritable cancer-specific alterations may be triggered by mutational and/or non-mutational changes in the genome that affec...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21861
更新日期:2013-04-01 00:00:00
abstract::Cell senescence and programmed cell death (apoptosis) are two fundamental biological mechanisms that regulate proliferative capacity, survival potential, aging, and death of cells. Here we report several independent lines of experimental evidence that support the hypothesis that telomerase function and telomere length...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::Patients with advanced hepatocellular carcinoma (HCC) continue to have a dismal prognosis. Potential biomarkers to determine prognosis and select targeted therapies are urgently needed for patients with HCC. This study aimed to elucidate the role of UCK2 in HCC prognosis and tumor progression. We performed a screen of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22954
更新日期:2019-04-01 00:00:00
abstract::Resistance to cisplatin-based chemotherapy is responsible for the majority of deaths from head and neck squamous cell carcinoma (HNSCC). In this study, using genome-wide gene expression analysis to investigate potential molecular mediators of HNSCC chemoresistance, we identified SERPINB2, a known inhibitor of extracel...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22033
更新日期:2014-10-01 00:00:00
abstract::We have reported that connexin (Cx) 32 gene, a member of gap junction protein family, acts as a tumor suppressor gene in human renal cell carcinoma (RCC). Of solid tumors, RCC is one of the most chemoresistant cancers, and there is no effective cancer chemotherapy against RCC at present. In this study, we examined if ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20267
更新日期:2007-03-01 00:00:00
abstract::Elevation of the steady-state mRNA levels of glucose transporter and c-myc are among the earliest changes in gene expression observed after Ha-rasT24 stimulation of Rat-1 fibroblasts to enter the cell cycle. Since the expression of these genes may be the result of either increased cell proliferation or a specific resp...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040406
更新日期:1991-01-01 00:00:00
abstract::We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20856
更新日期:2012-11-01 00:00:00
abstract::microRNAs (miRNA) silence target genes through Watson-Crick based binding to the 3'untranslated regions (3'UTR). Thus, polymorphisms in the miRNA-binding sites may disrupt this process and play a potential role in cancer pathogenesis. Integrins have been implicated in the genesis and development of many tumors. This s...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21973
更新日期:2014-04-01 00:00:00
abstract::We examined the expression of two groups of matrix metalloproteinases (MMPs), stromelysin and interstitial collagenase, in human skin cancer by northern blot analysis and in situ hybridization. Stromelysin-3 (ST-3) mRNA was overexpressed more than tenfold in 17 of 19 (89%) specimens of basal cell carcinoma (BCC) but i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090105
更新日期:1994-01-01 00:00:00
abstract::We examined whether betulin, a naturally abundant compound, has anticancer functions in human cancer cells. The results showed that betulin significantly inhibited cell viability in cervix carcinoma HeLa cells, hepatoma HepG2 cells, lung adenocarcinoma A549 cells, and breast cancer MCF-7 cells with IC(50) values rangi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20638
更新日期:2010-07-01 00:00:00
abstract::C>T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C>T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas st...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22623
更新日期:2017-06-01 00:00:00