bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 880: Polymorphisms of PLCE1 and KIF1B and risk of squamous cell carcinoma of the head and neck
Authors: Ma Hongxia , Wang Li-E , Liu Zhensheng , Sturgis Erich M , Wei Qingyi 
Published: June 2012

Abstract
Recent genome-wide association studies (GWAS) of gastric cancer, esophageal squamous cell carcinoma and hepatocellular carcinoma have identified PLCE1 and KIF1B as novel cancer susceptibility genes. In this study, we investigated associations between risk of squamous cell carcinoma of the head and neck (SCCHN) and potentially functional variants in PLCE1 and KIF1B. Three single nucleotide polymorphisms (SNPs, rs2274223G&gt;A, rs3203713G&gt;A and rs11599672T&gt;G) of PLCE1 and four SNPs (rs17401966A&gt;G, rs1002076G&gt;A, rs17401588A&gt;G and rs1536262C&gt;T) of KIF1B were genotyped by Taqman in 1,098 patients with SCCHN and 1,090 cancer-free controls, who were non-Hispanic whites matched by age (± 5 years) and sex. Although none of three SNPs of PLCE1 was alone significantly associated with overall risk of SCCHN, the combined genotypes [the number (0-6) of putative risk alleles (rs2274223G, rs3203713G and rs11599672G)] had a significant locus-dose effect on risk of SCCHN (Ptrend=0.046), particularly of non-oropharyngeal cancers (P trend=0.017), suggesting a joint effect of these SNPs on susceptibility to SCCHN. Further, the subgroup analysis showed that variant genotypes of rs2274223 and rs11599672 were independently associated with risk of non-oropharyngeal cancers, respectively. Of four SNPs of KIF1B, we found that rs1536262 variant had a significant association with the increased risk of SCCHN (additive model: adjusted OR = 1.15, 95% CI = 1.02-1.30) and the association was more evident in older subjects, females, former smokers, subjects with tumors of hypopharynx/ larynx, and subjects with poor progression tumor. Rs1536262 is located in 3’UTR region of KIF1B, a potentially functional SNP that may affect the binding of miRNA. Continuous efforts are underway in our laboratory to investigate potentially functional significance of rs1536262 in the development of SCCHN. In conclusion, our findings implicated a possible role of PLCE1 and KIF1B variants in the susceptibility to SCCHN, but larger studies are needed to validate our findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 880. doi:10.1158/1538-7445.AM2011-880
Abstract 888: Genetic variability in lipid metabolism and risk of lung cancer
Authors: Zhang Jianjun , Tanaka Hideo , Ito Hidemi , Boffetta Paolo , Matsuo Keitaro 
Published: June 2012

Abstract
Lung cancer is the leading cause of cancer death in many countries across the world. A growing body of evidence indicates that fat (especially saturated fat) is involved in lung carcinogenesis. Lung cancer incidence is higher among countries with high intake of fat. Some, although not all, epidemiologic studies have shown that fat intake was associated with an increased risk of lung cancer. Animal studies demonstrated that fat interacted with tobacco carcinogens to influence occurrence of lung tumors. Collectively, it is possible that genetic variability in lipid metabolism may modulate the risk of lung cancer. We sought to investigate this hypothesis in a hospital-based case-control study conducted from 2000 to 2005 in Nagoya, Japan. Cases (n=230), ages 20-79, were patients pathologically diagnosed with lung cancer at the Aichi Cancer Center, and controls (n=230) were recruited from visitors to the outpatient department of the Aichi Cancer Center and matched to cases by age (within 5 years) and sex. We genotyped polymorphisms in five genes: pancreatic lipase (PNLIP, rs2915748), apolipoprotein E (APOE, rs440446), hepatic lipase (LIPC, rs1800588), fatty acid desaturase 1 (FADS1, rs174546), and FADS (rs174570). Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated with unconditional logistic regression. After adjustment for age, sex, BMI, cigarette smoking (pack-years), a promoting effect was observed for the variant allele of PNLIP rs2915748 [OR (95%CI): 1.64 (1.09-2.47) for GA/AA vs. GG]. A similar effect was found for APOE rs440446 [OR (95%CI): 1.71 (1.14-2.58) for CG/GG vs. CC)]. No significant associations were detected for other three sequence variants examined. To our knowledge, our study is among the first to suggest that genetic variations in the digestion and transport of lipids alter lung cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 888. doi:10.1158/1538-7445.AM2011-888
Abstract 889: An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs
Authors: Yu Hongping , Zhao Hui , Wang Li-E , Han Younghun , V. Chen Wei , Amos Christopher I. , Rafnar Thorunn , Sulem Patrick , Stefansson Kari , Landi Maria Teresa , Caporaso Neil , Albanes Demetrius , Thun Michael , McKay James D. , Brennan Paul , Wang Yufei , Houlston Richard S , Spitz Margaret R. , Wei Qingyi 
Published: June 2012

Abstract
DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumamHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1,154 lung cancer cases and 1,137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test = 4.89 ×10−4). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test = 1.3 ×10−3). A luciferase reporter assay demonstrated that the rs2075685G&gt;T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR = 0.80, 95% CI = 0.62-1.03, P = 0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR = 0.77, 95% CI = 0.66-0.89, Pdominant = 5×10−4 and P for trend = 5×10−4) and rs1478486 (adjusted OR = 0.82, 95% CI = 0.71 -0.94, Pdominant = 6×10−3 and P for trend = 3.5×10−3). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 889. doi:10.1158/1538-7445.AM2011-889
Abstract 89: Prostaglandin E2 promotes intestinal tumor growth via DNA methylation
Authors: Xia Dianren , Wang Dingzhi , Kim Sun-Hee , DuBois Raymond N. 
Published: June 2012

Abstract
Evidence for the link between inflammation and cancer comes from epidemiologic and clinical studies showing that use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the relative risk for developing colorectal cancer (CRC) by 40-50%. NSAIDs exert some of their anti-inflammatory and anti-tumor effects by targeting cyclooxygenase enzymes (COX-1 and COX-2). COX-2-derived prostaglandin E2 (PGE2) is a pro-inflammatory mediator and promotes tumor progression. Clearly, DNA methylation is one of the critical mechanisms for silencing tumor suppressors and DNA repair genes during CRC initiation and progression. It has been demonstrated that a unique subset of CRC patients with extensive CpG island hypermethylation has unique clinicopathologic features and an exceedingly poor survival. However, all of the mechanisms by which chronic inflammation contributes to carcinogenesis are not understood and the precise role of aberrant DNA methylation in cancer also remains unclear. Here we used colorectal cancer cells to show that PGE2 treatment upregulated the expression of DNA methyltransferase 1 (DNMT1) and 3B (DNMT3B), which resulted to increased DNA methylation in the promoters of target genes O6-methylguanine-DNA methyltransferase (MGMT) and cannabinoid receptor 1 (CB1). Meanwhile, the expression of MGMT and CB1 were decreased. In ApcMin/+ mice, PGE2 treatment also increased the expression of DNMT1 and DNMT3B and the DNA methylation of MGMT and CB1 promoters, and reduced the expression of MGMT and CB1. All these alterations were accompanied by increases in both polyp number and size in the intestines of ApcMin/+ mice. More intriguingly, a combined treatment with a selective COX-2 inhibitor (celecoxib) and a demethylating agent (5-Aza-dC) significantly further reduced the polyp number and size in ApcMin/+ mice in comparison with single agent treatment. These results suggest that PGE2 can silence tumor suppressors and DNA repair genes via DNA methylation to promote tumor formation and progression. These findings uncover a previously unrecognized role for PGE2 promotion of tumor formation and progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 89. doi:10.1158/1538-7445.AM2011-89
Abstract 90: A comprehensive analysis to screen for epigenetically silenced miRNA genes in colorectal cancer
Authors: Suzuki Hiromu , Yamamoto Eiichiro , Nojima Masanori , Shimizu Takashi , Tokino Takashi , Shinomura Yasuhisa , Toyota Minoru 
Published: June 2012

Abstract
Epigenetic alteration plays an important role in inactivating microRNA (miRNA) genes in cancer. In the present study, we performed comprehensive analysis of miRNA expression, histone modification and DNA methylation in order to determine the transcription start sites (TSSs) of miRNA genes as well as to identify epigenetically silenced miRNA genes in colorectal cancer (CRC). We used a CRC cell line HCT116 treated with our without 5-aza-2’-deoxycytidine (DAC) plus 4-phenylbutyric acid (PBA). We also used a HCT116 cells in which DNMT1 and DNMT3B are genetically disrupted (DNMTs KO). For miRNA expression profiling, we used Human miRNA Microarray v1 (Agilent Technologies) and TaqMan MicroRNA Array v2.0 (Applied Biosystems). We carried out chromatin immunoprecipitation (ChIP) using antibodies against trimethyl-histone H3K4 (H3K4me3), trimethyl-histone H3K27 (H3K27me3) or dimethyl-histone H3K79 (H3K79me2). We performed ChIP-on-chip analysis using Human Promoter ChIP-on-chip microarray (Agilent Technologies) and ChIP-seq analysis using SOLiD3plus (Applied Biosystems). DNA methylation was analyzed using methylated-specific PCR (MSP), bisulfite-pyrosequencing and methylated-CpG island amplification microarray (MCAM). miRNA microarray analysis revealed that 187 miRNAs were downregulated in HCT116 cells compared to normal colon, and more than half of the downregulated miRNAs were upregulated by demethylating treatment. By combining miRNA expression and H3K4me3 analysis, we identified presumed TSSs of 173 primary miRNA genes which encode 266 pre-miRNAs. Of the 266 pre-genes, TSSs of 114 genes are located in the proximal upstream (&lt; 5 kb) of pre-miRNA-coding regions, and TSSs of 213 genes are associated with CpG islands (CGIs). Comparison between HCT116 and DNMTs KO cells suggested that 39 primary genes which encode 87 pre-miRNAs are epigenetically silenced in HCT116. Of the 38 genes, TSSs of 24 genes are associated with CGIs, and we observed hypermethylation in all of them. We conclude that the combined analysis of expression, histone modification and DNA methylation is a useful strategy to identify epigenetically silenced miRNA genes in cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 90. doi:10.1158/1538-7445.AM2011-90
Abstract 908A: RAD51C germline mutations in breast and ovarian cancer cases from high-risk families
Authors: Clague Jessica N. , Wilhoite Greg , Adamson Aaron , Weitzel Jeffrey N. , Neuhausen Susan L. 
Published: June 2012

Abstract
Purpose: BRCA1 and BRCA2 account for approximately 80% of cases of hereditary breast and ovarian cancer. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene RAD51C, essential for homologous recombination repair, has been reported to be a rare breast cancer susceptibility gene. Several pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families but not in families with breast cancer alone.
Methods: We performed complete sequencing of RAD51C in germline DNA of 286 female breast and ovarian cancer cases with a family history of breast and ovarian cancer. They had been previously tested for mutations in BRCA1 and BRCA2 and were negative. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancer. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of non-synonomous variants. Two-hybrid screening is currently being performed to assess functionality of four of the non-synonomous variants.
Results: Fifteen DNA sequence variants were identified among the 286 cases; including four intronic, one 5’ UTR, one promoter, three synonymous, six non-synonymous variants. None were truncating. Of these variants, six have been previously identified and have rs numbers, whereas the remaining nine are novel. Nine of the variants were private (seen in one individual) and the other six were detected in more than one individual. Of the six non-synonomous variants, SIFT and Polyphen predicted that two were likely pathogenic, with predictions based on degree of conservation of the affected residue. An additional two non-synonomous variants are in important domains of the protein and may also be pathogenic. We are currently investigating potential functional importance of these four variants through yeast-two-hybrid assays.
Conclusions: Our results provide further evidence that Rad51C is a breast and ovarian cancer susceptibility locus.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 908A. doi:10.1158/1538-7445.AM2011-908A
Abstract 909: Activation of NF-κB and its downstream targets play a key role in the dramatic induction of hepatocarcinogenesis in metallothionein null mice
Authors: Kaffenberger Thomas , Roy Satavisha , Wang Bo , Costinean Stefan , Frankel Wendy , Bratasz Anna , Kuppusamy Periannan , Hai Tsonwin , Ghoshal Kalpana , Jacob Samson , Majumder Sarmila 
Published: June 2012

Abstract
Hepatocellular Carcinoma (HCC) is one of the most prevalent cancers in the world and the third leading cause of cancer-related death. Although hepatitis C and fatty liver disease appear to be the main risk factors in most western countries other factors including alcohol, tobacco, diabetes, and other metabolic disorders can also increase the likelihood of HCC development. HCC is believed to develop through a tumor promoting mechanism involving inflammation and oxidative stress. We have previously shown that metallothionein (MT), a ubiquitously expressed free radical scavenger, is dramatically downregulated in human and rodent HCCs. To test the hypothesis that MT protects the liver from carcinogenesis by relieving oxidative stress, MT knockout (MTKO) mice were injected with Diethylnitrosamine (DEN), a potent liver carcinogen. When compared to wild-type DEN treated mice, the MTKO groups exhibited significantly higher (5-fold) incidence and an accelerated rate of hepatocarcinogenesis. Gene expression analysis at the preneoplastic stage revealed a dramatic increase in the levels of Serpine-1 in the MTKO mice, which was validated by real-time PCR. Serpine-1, a tissue glycoprotein and an active suppressor of fibrinolysis through the inhibition of tissue plasminogen activator and urokinase plasminogen activator, is also believed to increase cell migration and angiogenesis. Real-time PCR analysis of the pro-inflammatory cytokines known to induce Serpine-1 revealed substantial upregulation of TNF-α, IL-6, and IL-1β in the MTKO/DEN mice compared to the WT/DEN and untreated controls. Electrophoretic mobility shift assay confirmed differential activation of NF-κB, a downstream effector of pro-inflammatory cytokines and inducer of Serpine-1 expression, in the MTKO/DEN mice at the preneoplastic stage. These data demonstrate that Serpine-1 and NF- κB act in concert at the early stages of hepatocarcinogenesis when free radical scavenging is compromised. These data show the protective role of MT against HCC induction in a mouse model and provide the rationale for an alternate therapeutic strategy in HCC therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 909. doi:10.1158/1538-7445.AM2011-909
Abstract 913: Differential roles of SPARC in bladder carcinogenesis and metastasis
Authors: Said Neveen A. , Frierson Henry , Theodorescu Dan 
Published: June 2012

Abstract
Secreted Protein Acidic and Rich in Cysteine (SPARC), also termed osteonectin and BM-40, exhibits highly regulated expression during normal development, in tissues undergoing remodeling and repair as well as in cancer. The role of SPARC in bladder cancer is still elusive. Therefore, we sought to investigate the differential roles of SPARC in bladder carcinogenesis, progression and metastasis. We developed a chemical carcinogen N-nitrosobutyl(4-hydroxybutyl) amine (BBN) fed to mice with targeted deletion of SPARC (SP−/−) and their wild type counterparts (SP+/+) in drinking water to induce bladder cancer. We found that SP−/− mice exhibited earlier onset of urothelial pathology (inflammation/atypia and dysplasia, P&lt;0.01) that significantly rapidly progressed to carcinoma in situ (CIS, P&lt;0.02) and muscle invasive disease (P&lt;0.03) as compared to their SP+/+ counterparts. SP−/− mice also exhibited significantly higher incidence and frequency of multifocality (kidney involvement, P&lt;0.02) as well as metastases to para-aortic lymph nodes (P&lt;0.04) and lungs (P&lt;0.03) than SP+/+ counterparts. Furthermore, SP−/− mice had significantly lower median survival than SP+/+ counterparts (27weeks versus 40weeks for SP−/− and SP+/+, respectively; P&lt;0.0002). Comparative analysis of bladder tissue lysates harvested from SP−/− and SP+/+ mice with matched pathology and BBN-exposure revealed that the accelerated onset of bladder lesions in SP−/− compared to SP+/+ was due to the effect of SPARC inhibiting cell cycle progression. These effects correlated with increased accumulation of reactive oxygen species concomitant with DNA damage as determined by 8-OH-odeoxyguanosine, lipid peroxidation and increase in markers of protein oxidation, sulfiredoxin and nicotinamide-N-methyl transferase (NNMT). The significant increase in inflammation in SP−/− was associated with significant higher activation of transcription factors AP1 and NFκß compared to SP+/+. These findings indicate SPARC exerts distinct differential roles in modulating tumor-host interactions during the initiation, progression and lung metastasis of bladder cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 913. doi:10.1158/1538-7445.AM2011-913
Abstract 914: The role of CD44 variant in the development of spasmolytic polypeptide-expressing metaplasia (SPEM) and gastric cancer
Authors: Wada Takeyuki , Nagano Osamu , Ishimoto Takatsugu , Oshima Hiroko , Oshima Masanobu , Masuko Takashi , Baba Hideo , Kitagawa Yuko , Saya Hideyuki 
Published: June 2012

Abstract
CD44 is a marker of tumor-initiating cells in gastric cancer. However, the cause or consequence of elevated CD44 in such immature tumor cells is not known. Gastric carcinogenesis involves a transition from normal mucosa to gastritis, which then leads to metaplasia and eventually adenocarcinoma. Although the emergence of metaplasia or dysplasia is a key event of inflammation-related gastric carcinogenesis, the precise mechanism underlying the transition from normal gastric epithelium to metaplasia and cancer remains unsolved. Spasmolytic polypeptide (known as trefoil factor family 2)-expressing metaplasia (SPEM) results from a metaplastic change of gastric epithelial cells in response to chronic inflammation. Here we show that the trefoil factor family 2 (TFF2)+ metaplastic glands as well as gastric tumor glands contain CD44 variant isoform-expressing (CD44v+) cells in K19-Wnt1/C2mE mouse, a genetic mouse model for gastric tumorigenesis. Furthermore, the analysis of three transgenic mouse lines K19-Wnt1, K19-C2mE and K19-Wnt1/C2mE revealed that de novo expression of CD44v in SPEM cells is triggered by prostaglandin E2-mediated signaling. Isolated CD44-expressing tumor cells in K19-Wnt1/C2mE mice by fluorescence-activated cell sorting (FACS) manifested increased expression of SPEM-related genes, suggesting that metaplastic epithelium might give rise to both of CD44v+ tumor cells and CD44v+ SPEM cells in mice. To investigate the role of CD44 in the development of SPEM and gastric tumor in mice, we generated CD44-/- K19-Wnt1/C2mE mice. We found that CD44 ablation significantly suppresses the development of SPEM and gastric tumor, suggesting that CD44v+ cells play a key role in gastric tumorigenesis. Furthermore, we found that the emergence of CD44v+ SPEM glands adjacent to cancer is tightly associated with the CD44v-expressing gastric cancer formation in human. Our present study thus suggest that SPEM cells might be susceptible for oncogenesis due to their proliferative capacity and that CD44v+ SPEM cells are cells-of-origin for CD44v+ tumor-initiating cells in human gastric adenocarcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 914. doi:10.1158/1538-7445.AM2011-914