bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4481: Vitamin D pathway gene variants associated with vitamin D deficiency in African Americans
Authors: Batai Ken , Shah Ebony , Ruden Maria , Newsome Jennifer , Murphy Adam , Kittles Rick A. 
Published: August 2012

Abstract
Background: Cancer incidence and mortality rate is disproportionate among the racial/ethnic groups in the U.S. and higher in African Americans (AAs) due to a combination of genes and environmental factors. The difference in serum vitamin D3, 25(OH)D, concentration among racial groups is suspected to be one of the sources of cancer health disparities. Vitamin D has protective effects against several types of cancer, and vitamin D deficiency is more common among AAs than the European Americans (EAs). Genome-Wide Association Studies (GWAS) among EAs found vitamin D pathway gene (VDPG) variants associated with serum 25(OH)D level, but association between VDPG variants and serum 25(OH)D level has not examined in AAs. Here, we tested if thirty-nine VDPG variants are associated with serum 25(OH)D concentration. Samples and Methods: Nineteen variants in GC, VDR, CYP3A4, CYP2R1, and CYP24A1 were genotyped in a total of 462 AAs from Washington, D.C. and Chicago area. Twenty GWAS identified VDPG variants were genotyped in a subset of subjects (n=332). West Africa Ancestry (WAA) was estimated using STRUCTRE from 105 ancestry informative markers typed. Then, we tested for association adjusting for WAA, age, and skin color. Results: Eight GWAS identified SNPs (five in GC, one in CYP2R1, and two in DHCR7/NADSYN1) were associated with serum 25(OH)D levels and/or vitamin D deficiency. Among darker-skinned AAs, the VDR SNP rs11568820 (Cdx2), was significantly associated (P&lt;0.05) with the risk of vitamin D deficiency (&lt;20 ng/ml) (OR=1.94; CI 1.11-3.38). Conclusion: We found VDPG variants associated with serum 25(OH)D level and/or vitamin D deficiency in AAs. We also replicated the findings from a previous GWAS in EAs and found that the same variants were associated with serum 25(OH)D in AAs. Additional studies are necessary to assess whether these variants are associated with cancer risk. Impact: Increased attention is focused on the role of vitamin D in cancer risk. Our findings provide insights on the biological and environmental modifiers of serum vitamin D3 and will help guide future studies on the role of vitamin D in cancer in high risk populations such as AAs.
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 4481. doi:1538-7445.AM2012-4481
Abstract 4485: Prediction of esophageal cancer risk through quantification of gamma-H2AX levels in peripheral blood lymphocytes
Authors: Zhang Fanmao , Gu Jian , Gong YiLei , Hawk Ernest , Ajani Jaffer A. , Wu Xifeng 
Published: August 2012

Abstract
Increased susceptibility to DNA damage has been shown to be associated with increased risk of many cancers. Accumulation of gamma-H2AX (γ-H2AX) in cultured cells after stimulation by ionizing radiation or other genotoxic agents is a sensitive indicator of DNA double-strand breaks (DSBs) induction. We hypothesize that higher level of DSBs, as measured by γ-H2AX levels in peripheral blood lymphocytes (PBLs), may be able to predict higher cancer risk. We first developed an objective, high-throughput, and image-based method to quantify immunofluorescence intensities of γ-H2AX in cultured PBLs. To test this hypothesis, using an ongoing esophageal cancer case control study, we measured the γ-H2AX levels at baseline and after gamma-radiation in the PBLs from 245 newly diagnosed, previously untreated esophageal cancer patients and 400 healthy control subjects, and calculated the ratio of radiation-induced to the baseline γ-H2AX levels as a parameter of DSBs. The mean γ-H2AX ratio was significantly higher in cases (1.48±0.14) than controls (1.39±0.11) (P =1.47×10-14). When dichotomized at the median level of the γ-H2AX ratio in control subjects, individuals in the high γ-H2AX ratio group exhibited a significantly increased risk of esophageal cancer (odds ratio [OR]=2.83, 95% confidence intervals [CI]: 2.00-4.00). When subjects were categorized into tertiles defined by the distribution of the relative γ-H2AX ratio in control subjects, a significant dose-response relationship was observed between γ-H2AX ratio and risk of esophageal cancer. Compared to subjects in the lowest tertile of γ-H2AX ratio, those in the middle and the highest tertiles exhibited increased risks of esophageal cancer with ORs of 1.60 (95% CI: 1.00-2.55) and 3.72 (95% CI: 2.43-5.70), respectively (P for trend =2.24×10-10). Quartile analysis also showed similar dose-response relationship. Our data suggest that higher ratio of gamma-radiation-induced to baseline γ-H2AX is significantly associated with an increased risk of esophageal cancer. This study supports that measurement of this ratio may be used as a novel phenotypic assay to identify individuals at high risk for esophageal cancer.
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 4485. doi:1538-7445.AM2012-4485
Abstract 4487: Inverse associations between soluble cytokine receptors and colorectal cancer risk
Authors: Ho Gloria YF , Xue Xiaonan , Zheng Lilly S. , Cushman Mary , Xu Jianfeng , Tinker Lesley , Wang Tao , Wassertheil-Smoller Sylvia , Strickler Howard D. , Gunter Marc J. , Rohan Thomas E. 
Published: August 2012

Abstract
Laboratory studies have suggested that soluble receptors of proinflammatory cytokines could be anti-inflammatory by acting as decoy receptors, blocking binding of the cytokines to their membrane receptors, and hence inhibiting cytokine signaling. Thus, relatively high levels of soluble cytokine receptors and receptor antagonists may be protective factors against colorectal cancer, which is an inflammation-associated disease. This case-cohort study nested within the Women's Health Initiative Observational Study of postmenopausal women 50-79 years of age at baseline (1993-1998) examined whether baseline plasma levels of IL-1 receptor antagonist (IL-1Ra) and the soluble receptors of IL-6 (sIL-6R and sgp130), TNF (sTNF-R1 and sTNF-R2), and IL-1 (sIL-1R2) were inversely associated with colorectal cancer risk. Analytes were measured in 433 incident colorectal cancer cases and 823 subcohort members using multiplex assays (Millipore, Billerica, MA). Circulating levels of IL-6, TNF-α, insulin, and estradiol measured previously were also available for data analyses. IL-1Ra and the 5 soluble receptors did not correlate with each other or with their ligands (all correlations r &lt; 0.3), with the exception of sTNFR2, which was moderately correlated with sTNFR1 (r=0.51) and TNF-α (r=0.43). The table below shows the hazard ratios for colorectal cancer risk, when each analyte was entered separately into a Cox regression model adjusting for other colorectal cancer risk factors. Colorectal cancer risk decreased significantly with increasing levels of sIL-6R and sIL-1R2. The ratios of IL-6 or TNF-α to their soluble receptors were not associated with colorectal cancer risk. There were also no significant interactions between pairs of soluble receptors or between soluble receptors and their ligands. Increased circulating levels of sIL-6R and sIL-1R2 may confer protection against colorectal cancer. If our results are confirmed, these soluble receptors can be considered for chemoprevention.

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 4487. doi:1538-7445.AM2012-4487
Abstract 449: Detection of some selected tumor markers in people from River Nile State - Sudan
Authors: Ali Eltayeb A. , Hassan Osman Mahgoub , Ahmed Mohamed Abdallah 
Published: August 2012

Abstract
This study was designed to use some selected tumor markers (TMs) as screening tool to discover new cancer cases, and to use these TMs as diagnostic tool for early detection of cancer. The study area is the River Nile State with an area of 122100 Km2 and population of 1026000 persons. The national cancer control program was initiated in 1982 with WHO help, and updated in the early 1990s based on the new WHO guidelines. In 2010 the National Cancer Registry was established but still more efforts are needed to register all cancer cases in such a poor country like Sudan. According to Federal Ministry of Health (FMOH) 2008 data; cancer was ranked as the fourth cause of death in hospitals. Five hundred and ten blood samples were collected from healthy people living in River Nile State; 305 samples were males. (PSA) was measured in all males, (CA125) was used for ovarian cancer in females, (CA15-3) was used for breast cancer in females, and (CEA) Carcino Embryonic Antigen was used for colon cancer in both genders. Samples were measured using RIA technique. Written consent was obtained from all volunteers. There was an elevation in blood level of CEA in 26 samples (6.37%), two of them died during the study, 7 (2.29%) males had PSA concentrations above the upper limit, 5 (2.45%) females showed high CA15-3 concentrations, and increase in CA125 in 6 samples (2.94%). Out of the 510 subjects there were 56 samples (10.98%) had family history with cancer, and only 6 of them (10.71%) showed elevated concentrations. Most of these people are very poor and hospitals are not accessible and the diagnosis and treatment services are not affordable. Table 1 shows the concentrations for the selected TMs.The FMOH documented in 2007 that more than 345 cancer patients came from River Nile State, more cases were reported in other studies e.g. 2899 cancer incidences in Northern Sudan in 2006. In the present study, (8.63%) of the studied population showed elevated concentrations of the selected TMs. Table 1: TMs concentrations.

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 449. doi:1538-7445.AM2012-449
Abstract 4492: Colorectal cancer survival by molecular subtypes in a population-based cohort of older women
Authors: Vierkant Robert Alan , Tillmans Lori S. , Wang Alice H. , Samadder Niloy Jewel , Weisenberger Daniel J. , Laird Peter W. , Lynch Charles F. , Anderson Kristin E. , French Amy J. , Haile Robert W. , Harnack Lisa J. , Potter John D. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R. , Limburg Paul J. 
Published: August 2012

Abstract
Background: Despite recent advances in prevention and therapy, colorectal cancer (CRC) continues to account for nearly 50,000 deaths per year in the US. TNM stage is the current CRC prognostic standard, yet within-stage prognostic heterogeneity is well documented. Microsatellite instability (MSI), CpG island methylation phenotype (CIMP), and BRAF- and KRAS-mutation status represent candidate prognostic markers. However, associations between these markers and CRC survival have not been described in a population-based setting. Methods: Data and tissue resources were obtained from the Iowa Women's Health Study (IWHS), which recruited 41,836 women, ages 55-69 years, at study entry (1986). Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected from 732 representative CRC cases diagnosed through 12/31/2002. Established laboratory methods were used to characterize CRC cases: MSI-H or MSS/MSI-L (by instability in β3 vs. &lt;3 out of 10 markers, respectively); CIMP+ or CIMP− (by promoter hypermethylation in β3 vs. 0-2 out of 5 genes, respectively); BRAFwt or BRAFmut (by fluorescent allele specific PCR to detect the V600E point mutation in exon 15); and KRASwt or KRASmut (by direct sequence analysis of codons 12 and 13 in exon 2). Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for time to death of any cause adjusted for age, stage, grade, and treatment status. Results: CRC cases with informative molecular marker data ranged from 515/732 (70%) for KRAS to 548/732 (75%) for MSI status. Mean follow-up was 4.4 years for deceased individuals and 11.2 years for women alive at last contact. After multivariable adjustment, both MSS/MSI-L (p=0.004) and KRASmut (p=0.048) tumors were associated with poorer survival. Survival did not significantly differ across levels of CIMP and BRAF status. Conclusions: MSI and KRAS status may influence CRC survival 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 4492. doi:1538-7445.AM2012-4492
Abstract 4496: UBCH10 overexpression in human colorectal cancers
Authors: Piscuoglio Salvatore , Pallante Pierlorenzo , Tornillo Luigi , Fusco Alfredo , Terracciano Luigi Maria 
Published: August 2012

Abstract
Background: Colorectal cancer is the result of the accumulation of different genetic modifications including critical genes involved in the control of cell proliferation. In a large number of carcinomas with worst prognosis, lesions are not diagnosed until the disease is at an advanced stage. To diagnose cancer at an early stage and to establish more effective therapies featuring of key molecules in carcinogenesis is a critical steps. UBCH10 (also known as E2C or UBE2C) is a cell cycle-related protein involved in mitosis completion. UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. Thus, UbcH10 is essential for cell cycle progression, and his expression is cell-cycle dependent and related to proliferation Aims: The aim of this study is to investigate the association of UbcH10 gene expression with clinicopathological features and tumor progression of colorectal cancer. Materials and methods: We investigated the expression of the UBCH10 genes in a tissue microarray platform consisting of normal and neoplastic colorectal cancers (CRC) tissues by immunohistochemistry. UBCH10 was detectable in 889 patients. Immunoreactivity was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Scores were assigned using 5% intervals and ranged from 0% to 100%. Median protein expression levels were used as cut-off scores to define protein marker positivity and the findings were associated with clinical-pathological parameters. Results: Our results demonstrated that UBCH10 is over-expressed in CRCs tissues compared to normal colon (p&lt;0,001), and more specifically the UBCH10 expression is significant higher in tumor location: left VS. right sided (p=0,005). Moreover we found a significant relationship between overexpression of UBCH10 with T stage (p&lt;0,001), N stage (p=0.022), tumor border configuration: pushing VS. infiltrating (p=0.035) and also UBCH10 over-expression was significantly correlated with shorter patient survival. Conclusion: Our study suggests that the overexpression of UbcH10 gene plays a critical role in the carcinogenesis and tumor progression of colorectal cancer. Also our findings indicate, that in colorectal carcinomas, low expression of UBCH10 may be linked to a more aggressive tumor phenotype.
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 4496. doi:1538-7445.AM2012-4496
Abstract 4499: Loss of ATM (distal chromosome 11q) as a prognostic marker in HPV-negative head and neck squamous cell carcinomas
Authors: Parikh Rahul A. , Lewis Dale W. , Gollin Susanne M. 
Published: August 2012

Abstract
Introduction: HPV-negative head and neck squamous cell carcinomas (HNSCC) represent a subset of head and neck cancers with poor response to treatment and worse prognosis compared to HPV-positive HNSCC. In our prior pre-clinical experiments with HNSCC cell lines, we demonstrated that copy number loss of ATM as a marker for loss of distal chromosome 11q loss leads to defectiveγ-H2AX focus formation, increased chromosomal instability, and reduced sensitivity to ionizing radiation. We hypothesize that in HPV-negative HNSCC, ATM loss is a biomarker for poor outcome. Methods: We performed a single center, retrospective analysis of 42 HNSCC patients to determine if ATM loss is associated with poor overall survival in HPV-negative HNSCC. We performed fluorescence in situ hybridization using probes to cyclin D1 (CCND1) and ATM to assess copy number changes in paraffin sections from HNSCC tumors. Disease-specific survival was defined as time from the date of tissue procurement (surgery or biopsy) until death from disease (HNSCC). Patients who were alive at last follow-up or had died from causes unrelated to their disease were censored. Disease-specific survival by ATM loss status was estimated by the Kaplan-Meier method and tested for a difference by a two-tailed log rank test. Three covariates, age, T stage and N stage were investigated and the effect of ATM loss upon disease-specific survival was assessed with proportional hazards regression by adjusting for these covariates as needed to determine if ATM loss could be considered independently associated with cancer mortality. Results and Conclusions: HPV-negative HNSCC patients with ATM copy number loss have a median disease-specific survival of only 19 months compared to 65 months for patients without ATM loss (log rank p = .0401). We investigated whether the association between ATM loss and disease-specific survival was due to the confounding influence of other clinical variables. Age and T stage were modestly associated with survival, but neither covariate was correlated with ATM loss. We estimated the hazard ratio for ATM loss alone and conditional upon age and T stage was unchanged (.040 alone vs .047 adjusting for age and T stage). Therefore, distal 11q loss, marked by copy number loss of ATM appears to increase the risk of disease-specific mortality independently of age, N stage and T stage. Our results demonstrate that ATM loss in HPV-negative HNSCC may be prognostic of poor outcome and novel therapeutic strategies may be required in this subset of patients. Further studies to elucidate the mechanisms of distal 11q loss and study potential treatment options are underway in our laboratory.
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 4499. doi:1538-7445.AM2012-4499
Abstract 450: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer
Authors: Okugawa Yoshinaga , Tanaka Koji , Inoue Yasuhiro , Kawamura Mikio , Matsushita Kouhei , Kawamoto Aya , Hiro Junichro , Saigusa Susumu , Toiyama Yuji , Ohi Masaki , Uchida Keiichi , Mohri Yasuhiko , Hori Hiroki , Kusunoki Masato 
Published: August 2012

Abstract
Purpose. Smad interacting protein 1 (SIP1) encodes a transcription factor and is one of the epithelial-mesenchymal transition (EMT)-inducible genes that play a key role in tumor progression in various cancers. The aim of this study is to clarify the clinical significance of SIP1 expression in gastric cancer patients, and to clarify its biological function especially in intestinal type gastric cancer. Methods. We studied one hundred thirty-four patients undergoing surgery for gastric cancer. We analyzed SIP1 mRNA levels by real-time reverse transcription PCR in gastric cancer tissue and adjacent normal mucosa, and in gastric cancer cell lines. SIP1 protein expression in primary cancer and in peritoneal dissemination samples was measured using immunohistochemical analysis. Knockdown of the SIP1 gene by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cell. Results. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa (p&lt;0.05). Increased SIP1 expression was significantly associated with peritoneal dissemination (p&lt;0.05), and was an independent prognostic factor (risk ratio, 2.17; 95% confidence interval, 1.26-3.74; p&lt;0.05). Logistic regression analysis revealed that increased SIP1 expression was an independent risk factor for peritoneal dissemination (odds ratio, 3.43; 95% confidence interval, 1.25-9.43; p&lt;0.05). Especially in intestinal type gastric cancer, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p&lt;0.05). Immunohistochemical analysis indicated that SIP1 was intensely expressed in both primary cancer and peritoneal dissemination samples. In vitro, cell proliferation, migration and invasion were inhibited by SIP1 knockdown, while resistance to anoikis was decreased after knockdown of SIP1 in the intestinal type gastric cancer cell line MKN7. Conclusion: High SIP1 expression is associated with poor prognosis especially in intestinal type gastric cancer patients and enhanced malignant potential in terms of proliferation, migration, invasion and anoikis inhibition in intestinal type gastric cacner cell. These results indicate that SIP1 plays an important role in progression to peritoneal carcinomatosis in intestinal type gastric cancer.
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 450. doi:1538-7445.AM2012-450