bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1640: Unidentified genetic variants influence pancreatic cancer risk: An analysis of the PanScan genome-wide association study
Authors: Pierce Brandon L. , Tong Lin , Kraft Peter , Ahsan Habibul 
Published: August 2012

Abstract
Genome-wide association (GWA) methods have been used to identify multiple pancreatic cancer susceptibility loci. However, it is likely that other unidentified common susceptibility variants exist. In this work we used data on 493,619 common autosomal single nucleotide polymorphisms (SNPs) from the PanScan GWA study (2,857 cases and 2,967 controls) to confirm the existence of unidentified susceptibility variants using two cross-validation methods: a polygenic risk score (PRS) approach and a power-replication approach. For the PRS approach, after excluding all SNPs from known pancreatic cancer susceptibility loci, we first constructed a polygenic risk models based on a training dataset and then tested the model in an independent testing dataset. The second approach (i.e., “power-replication) was based on calculating power to detect association for each SNP based on association estimates from a training set and then testing the power estimate for association with probability of replication in an independent testing data set. Using the polygenic risk score method, we demonstrate the existence of additional pancreatic cancer risk variants, the majority of which have P-values &gt; 0.01 in the PanScan study. We also demonstrate enrichment for unidentified loci near gene regions. We reach similar conclusions using the power-replications approach, where SNPs with higher power to detect association were more likely to be replicated in an independent dataset at P&lt;0.05, especially when analyses were restricted to SNPs in gene regions. While our results do not substantially improve pancreatic cancer prediction, they do provide further rationale for focusing association studies on genic regions and suggest that conducting larger GWA studies and innovative secondary analyses have the potential to reveal novel susceptibility loci.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1640. doi:1538-7445.AM2012-1640
Abstract 1652: Targetome profiling and genetic association analyses implicate miR-202 in follicular lymphomagenesis
Authors: Hoffman Aaron E. , Liu Ran , Zheng Tongzhang , Fu Alan , Slack Frank , Zhu Yong 
Published: August 2012

Abstract
Complex etiologic heterogeneity among non-Hodgkin's lymphoma (NHL) subtypes has made it difficult to identify risk factors for this disease. However, recent genetic association analyses, including two genome-wide association studies, suggest that genetic susceptibility to NHL may be strongest for the follicular lymphoma subtype. As recent studies have demonstrated that microRNAs (miRNAs) may be important in the etiology of many cancer types, including NHL, we performed a population-based genetic association study which identified a polymorphism in the precursor of miR-202 that is strongly associated with follicular lymphoma risk (rs12355840 in miR-202: PTREND = 0.006). An in vitro functional genetics assay demonstrated that the polymorphism is biologically active, and operates by altering the processing efficiency of the miR-202 precursor to the mature effector miRNA species. A ribonucleoprotein immunoprecipitation-microarray (RIP-Chip) assay, performed with an anti-AGO2 antibody followed by a whole-genome array, was used to characterize the miR-202 targetome, and selected targets were confirmed using a 3′UTR luciferase assay. Among the identified targets were several transcripts with relevance for tumorigenesis, including the miRNA biogenesis gene DICER1 and the lymphoma-associated cell cycle regulator and proto-oncogene SKP2. Both of these genes have been shown to be upregulated in lymphomas, which is consistent with our data, which show that the miR-202 risk allele is associated with diminished mature miR-202 levels in vitro. Taken together, these findings suggest that rs12355840 may represent a novel risk biomarker for follicular lymphoma, and implicate miR-202 in follicular lymphomagenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1652. doi:1538-7445.AM2012-1652
Abstract 1653: Genetic variation in the vitamin D pathway and risk for colorectal cancer in African Americans
Authors: Pibiri Fabio , Kittles Rick A. , Sandler Robert S. , Keku Temitope O. , Kupfer Sonia S. , LLor Xavier , Ellis Nathan A. 
Published: August 2012

Abstract
Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death in both sexes in the United States. There is a large disparity in both CRC incidence and survival between African Americans (AAs) and all other US racial groups. Differences in serum vitamin D levels could contribute to this disparity because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels. In addition, genetic variants in vitamin D-related genes could modify the association between vitamin D levels and CRC risk. Methods: We tested for associations between CRC and 39 single nucleotide polymorphisms (SNPs) in vitamin D-related genes (CYP27A1, GC, CYP3A4, CYP2R1, DHCR7/NADSYN1, VDR, CYP27B1 and CYP24A1). We genotyped 357 AAs cases and 443 AA controls from the North Carolina Colorectal Cancer Study. We calculated odds ratios (OR) using logistic regression, assuming an additive genetic model and controlling for age, gender, and ancestry. We also analyzed SNP associations for colon and rectal cancer cases separately. We analyzed linkage disequilibrium and haplotype association using Haploview. Results: Associations (p&lt;0.05) were detected between CRC and two SNPs in the vitamin D binding protein gene GC, rs3755967 (OR, 0.69; P = .039,) and rs16847024 (OR, 1.50; P = .047,). We also detected an association with a SNP in the 24-hydroxylase gene CYP24A1, rs73913755 (OR, 0.75; P = .034,), which degrades vitamin D. A trend for association was detected in the 25-hydroxylase gene CYP2R1, rs10741657 (OR, 0.79; P = .051), which converts cholecalciferol into calcidiol. When we analyzed colon and rectal cancers separately, only one SNP was associated with colon cancer whereas 9 SNPs were associated with rectal cancer. In particular, rs73913755 (OR, 0.39; P = 3 x 10-7) was statistically significant even after adjustment for multiple testing. Conclusion: We tested vitamin D-related SNPs and found suggestive evidence that they influence the risk of developing CRC in AAs, with differences in risk between the colon and rectum. Comparison of these data with data from US whites could shed light on disparities in these different US populations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1653. doi:1538-7445.AM2012-1653
Abstract 1664: A functional study of missense variants localized in the DNA binding domain of BRCA2
Authors: Guidugli Lucia , Pankratz Vernon Shane , Erding Catherine A. , Goldgar David E. , Couch Fergus J. 
Published: August 2012

Abstract
Genetic evidence of pathogenicity is not available for most missense mutations (Variants of Uncertain Significance (VUS)) detected in the DNA binding domain (DBD) of BRCA2 by clinical genetic testing. In the absence of this evidence, functional assays may be useful for classification of the clinical relevance of these VUS. We used a cell based Homology-Directed repair reporter assay to characterize 14 known pathogenic and 18 known non-pathogenic BRCA2 missense mutations and 34 VUS from the DBD of BRCA2. We transfected each full-length wildtype and mutant BRCA2 construct into V-C8 BRCA2 deficient cells along with an I-Sce1-expression plasmid, which induces a unique double strand break in an integrated DR-GFP reporter plasmid. The protein expression levels were evaluated by immunoprecipitation and Western blotting. The ability of each BRCA2 mutant to repair the induced break was evaluated by fluorescent activated cell sorting (FACS) for GFP. The HDR assay exhibited 100% (95% CI: 75.3% - 100%) sensitivity and 100% (95% CI: 81.5% - 100%) specificity for pathogenic missense mutations. Next, we developed a statistical classifier for prediction of the pathogenicity or non-pathogenicity of BRCA2 variants based on results from the HDR assay. Using known pathogenic and non-pathogenic variants as standards we computed the probability that each variant is pathogenic or non-pathogenic based on HDR activity. A probability of 99% in favor of pathogenicity correctly classified the known pathogenic mutations and the non-pathogenic variants. The evaluation of an additional 34 variants identified 18 variants as deleterious and eight as neutral. In summary the HR assay serves as a reliable high-quality surrogate for classification of VUS located in the BRCA2 DBD.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1664. doi:1538-7445.AM2012-1664
Abstract 1667: Pathway analysis of bladder cancer genome-wide association study identifies several novel pathways involved in bladder cancer development
Authors: Chen Meng , Ye Yuanqing , Dinney Colin P. , Wu Xifeng 
Published: August 2012

Abstract
Recent genome-wide association studies (GWAS) have identified multiple genetic variants associated with bladder cancer risk but only explain a small fraction of the inherited variability. A recurring problem in traditional GWAS analysis (i.e., single-SNP analysis) is the lack of consideration of biological pathways that contains network of genes with subtle, undetectable effect at the single SNP or single gene level. Application of innovative secondary analyses focusing on genes and pathways will complement and expand traditional GWAS analysis and identify novel genes and pathways that are associated with bladder cancer risk. We used the genome-wide scan data from MD Anderson's bladder cancer case control study to identify cellular signaling pathways involved in bladder cancer tumorigenesis. Gene set enrichment analysis (GSEA) was applied as a secondary analysis of our previous bladder cancer GWAS data. GSEA can detect subtle effects of multiple SNPs in the same gene set, and multiple genes in the same biological pathway, which are often missed in traditional GWAS analysis. Using three GSEA approaches (Gen-Gen, Aligator, and SNP Ratio Test), we consistently identified 18 pathways significantly associated with bladder cancer risk. The top pathways included two cell cycle pathways involved in the G1/S transition (PGenGen: 0.001, PAligator: 0.001, PSRT: 0.002), neural cell adhesion molecule (NCAM) pathway (PGenGen:&lt;0.001, PAligator: 0.020, PSRT: 0.014), platelet-derived growth factor (PDGF) induced intracellular pathway (PGenGen: &lt;0.001, PAligator: 0.026, PSRT: 0.006) and unfolded protein response pathway (PGenGen: 0.007, PAligator: 0.001, PSRT: &lt;0.001). We identified that CCNE1 rs8110447 and rs8102137 were the most significant SNPs and gene in the two cell cycle pathways. As previously reported in GWAS, CCNE1 at 19q12 is a hotspot for bladder cancer susceptibility. However, other pathways with known susceptibility genes, such as those containing GSTM1, were not significant in the GSEA analysis, suggesting that this approach has identified novel biological pathways involved in bladder cancer tumorigenesis. Future studies are needed to validate in independent population. Overall, these findings contribute to a coherent understanding of the overall gene networks involved in bladder cancer susceptibility as well as offer additional etiologic insights highlighting the specific genes and pathways involved.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1667. doi:1538-7445.AM2012-1667
Abstract 1672: Population prevalence of consensus translocations in follicular and mantle cell lymphomas
Authors: Hirt Carsten , Meier Manuela , Yu Kelly , Schüler Frank , Janz Siegfried , Dölken Gottfried , Rabkin Charles S. 
Published: August 2012

Abstract
Chromosomal translocations t(14;18)(q32;q21) of the anti-apoptotic gene BCL2 and t(11;14)(q13;q32) of the cell cycle regulatory gene cyclin D1 are hallmark mutations of follicular lymphoma (FL) and mantle cell lymphoma (MCL), respectively, both driven by the enhancer of the immunoglobulin heavy chain gene cluster IGH. These same translocations have also been detected at low frequency in peripheral blood lymphocytes (PBL) of clinically normal individuals, but association with risk of subsequent lymphoma remains to be determined. We therefore evaluated consensus PCR assays for these translocations towards development of potential blood screening tests of lymphoma risk. Formalin-fixed, paraffin-embedded tumor specimens were retrieved from 62 FL and 17 MCL diagnosed during a large population-based cancer screening trial. Lymphoma DNA was isolated from scrapings off glass slides and assessed for quality and quantity by quantitative real-time PCR amplification of the single copy reference gene KRAS. Samples were divided into three aliquots and tested with consensus primers to detect translocations within either the Major Breakpoint Region (MBR) on chromosome 18 or the Major Translocation Cluster (MTC) on chromosome 11, as appropriate. For MBR-positive reactions, PCR fragment length was estimated by agarose gel electrophoresis. Overall, 21 (34%) of 62 FL and 7 (44%) of 16 MCL were PCR-positive for the consensus translocation sequences. Translocation detection was highly dependent upon testing an adequate quantity of DNA, with 21 (45%) PCR-positives among 47 FL samples of at least 500 diploid genome equivalents vs. 0 (0%) positives among the remaining 15 FL (p&lt;.001). PCR fragment lengths were identical from replicate assays for all but one MBR-positive sample, which yielded two products differing by 30 base pairs. Within the FL group, PCR-positivity did not significantly differ among Working Formulation histologies, including 2 (15%) of 13 mixed small cleaved and large cell FL, 5 (36%) of 14 small cleaved cell FL, 6 (55%) of 11 large cell FL, 1 (100%) of 1 centroblastic lymphoma and 7 (30%) of 23 FL not otherwise specified. We confirmed that nearly half of FL and MCL with adequate samples in this population-based cohort study have consensus translocation sequences. Thus, translocation presence and/or frequency in stored pre-diagnostic PBL can be usefully examined for associations with risk of subsequent lymphoma. FL- and MCL-associated translocations in PBL are a potential target for cancer risk prediction and preventive intervention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1672. doi:1538-7445.AM2012-1672
Abstract 1676: Associations between hormone therapy with incident colorectal cancer by p53 protein expression in a population-based cohort of older women
Authors: Tillmans Lori S. , Vierkant Robert , Wang Alice , Lynch Charles , Anderson Kristin , French Amy , Haile Robert , Harnack Lisa , Potter John , Slager Susan , Smyrk Thomas , Thibodeau Stephen , Cerhan James , Limburg Paul 
Published: August 2012

Abstract
Background: Cigarette smoking (CS) is an established colorectal cancer (CRC) risk factor. The p53 protein, encoded by the TP53 tumor suppressor gene that is commonly mutated in CRC, is important in cell cycle arrest needed to repair DNA damage or induce apoptosis to prevent tumor propagation. In this prospective cohort study, we examined CS-associated CRC risks by p53 protein expression level in the population-based Iowa Women's Health Study (IWHS). Methods: The IWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry (1986). CS and other exposure variables were assessed at baseline, by self-report. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected from 732 CRC cases diagnosed through 12/31/2002. CS was categorized by smoking status (never, current, former), average number of cigarettes per day (1-19, 20-39, &gt; 40) and cumulative pack-years (1-19, 20-39, &gt; 40). P53 protein expression was determined by immunohistochemistry on tissue microarrays. Tumor cores were scored by combining both staining intensity and percent of cells stained to determine negative, low or high p53 protein expression levels. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: Of the 732 available CRC cases, 486 (66%) had complete CS and p53 data. Associations between CS and CRC subtypes defined by p53 expression level are shown in the Table. Conclusions: These data demonstrate no clear heterogeneity of CS with CRC subtypes defined by p53 expression levels among older women.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1676. doi:1538-7445.AM2012-1676
Abstract 1679: Genome-wide methylation analysis in Barrett's esophagus and esophageal adenocarcinoma
Authors: xu Enping , Gu Jian , Hawk Ernest T. , Huang Maosheng , Wang Kenneth K. , Ajani Jaffer A. , Wu Xifeng 
Published: August 2012

Abstract
Esophageal carcinogenesis (EAC) is a multiple-step process involving the accumulation of multiple genetic and epigenetic changes. Barrett's esophagus (BE) is a precursor of EAC. In this study, we performed genome-wide methylation profiling of BE and EAC tissues to identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of EAC. Using Illumina's HumanMethylation27 BeadChip microarray, we examined the methylation status of 27,578 CpG sites in 94 normal tissues, 77 BE, and 117 EAC tissues. Hierarchical clustering analysis showed an excellent separation of normal tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting the methylation pattern of BE and EAC was similar and methylation occurs early during the progression of EAC. At the individual gene level, we recapitulated the major tumor suppressors that previously reported to be hypermethylated in BE and EAC, including SFRP1, APC, WIF1, etc. We also identified a large number of novel hypermethylated genes in BE and EAC tissues, in particular, genes of several family proteins, including ADAM peptidase proteins, cadherin and procadherin, and potassium voltage-gated channels. We used pyrosequencing to validate selected genes in these families. For example, in normal, BE and EAC tissue, the methylation frequency of PCDH9 was 0.20%, 24.6% and 29.5% respectively, and the methylation frequency of ADAMTS2 was 4.69%, 37.3% and 32% respectively. In general, there were significant correlations between array and pyrosequencing results. The identified differentially methylated genes may become potential biomarkers for the prediction and early detection EAC among BE patients and molecular targets for prevention and therapy of EAC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1679. doi:1538-7445.AM2012-1679
Abstract 1691: A primer dose followed by low-bolus dose schedule of tumor-targeting of S. typhimurium A1-R is effective for tumor-targeted therapy
Authors: Tome Yasunori , Zhang Yong , Momiyama Masashi , Maehara Hiroki , Kanaya Fuminori , Tsuchiya Hiroyuki , Tomita Katsuro , Bouvet Michael , Hoffman Robert M. , Zhao Ming 
Published: August 2012

Abstract
The S. typhimurium A1-R mutant, which is auxotrophic for leu-arg, and selected for high antitumor virulence, has been shown to be effective as monotherapy against human prostate, breast, pancreatic, and fibrosarcoma tumors. In the present study, we developed a strategy to maximize efficacy and minimize toxicity for bacterial tumor treatment in immunocompetent mice with subcutaneous Lewis lung carcinoma expressing red fluorescent protein (RFP). A small dose of S. typhimurium A1-R bacteria was first administered to tumor-bearing animals (the primer dose, 1×106 cfu i.v.) as pre-treatment followed by a high dose (1×107 cfu i.v.) 4 hours later. Compared with non-primer-dose bacteria treatment, the primer-dose strategy resulted in smaller tumors and no observable side effects. The serum lever of TNF-α was elevated in the primer-dose arms compared to non-primer dose arms. Vessel destruction by S. typhimurium A1-R was observed in immunocompetent mice expressing nestin-driven green fluorescent protein (ND-GFP), which is selectively expressed in nascent blood vessels. Vessel destruction was enhanced in the primer-dose arms compared to non-primer-dose arms. The primer dose may activate the immune system and induce cytokines in the mouse necessary for invasion of the tumor by the bacteria allowing a relatively small subsequent dose to be effective and safe.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1691. doi:1538-7445.AM2012-1691