bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 471: RNAi target evaluation in clinically relevant murine model of colon cancer metastasis
Authors: Rychahou Piotr G. , Evers B. M. 
Published: February 2011

Abstract
Significant challenges remain before RNA interference (RNAi) becomes a reality in practice. Identifying the appropriate genes to target and evaluating these agents in clinically relevant animal models of metastatic cancer are critical. Short- and long-term side effects and potential in vivo toxicities of RNAi therapy are largely unknown due to lack of animal models to simultaneously evaluate RNAi effect on both cancer cells, tumor microenvironment and the host organism. The purpose of our present study was to establish a murine model for metastatic colon cancer which will allow us to evaluate the effect of RNAi on tumor metastases as well as potential side effects to the normal host. METHODS. Murine colon cancer cell lines, CT26 and MC26, expressing green fluorescent protein (GFP) were injected intrasplenically into either Balb/C or Swiss-Webster mice at concentrations of 1×106, 2.5×106 and 5×106 in a volume of 100 uL. Tumor growth and metastasis were monitored for 30 days. To demonstrate siRNA delivery into colon cancer metastasis to the liver, Cy3-labeled siRNA was used. siRNA formulated in DOTAP was administered via tail vein, and mice were sacrificed at 1, 4 and 24 h postinjection. Frozen-section fluorescence microscopy was used to evaluate siRNA delivery and distribution in metastatic liver tumors. RESULTS. We observed extensive metastases in Balb/C mice injected intrasplenically with CT26 cells. The optimal concentration for metastasis was 2.5×106 cells. No intrasplenic tumor growth or metastasis was observed in Swiss-Webster mice after intrasplenic CT26 tumor cell injection or in Balb/C and Swiss-Webster mice after MC26 injection. We also demonstrated Cy3-labeled siRNA delivery into metastatic liver tumors as early as 1 h postinjection. CONCLUSIONS. Intrasplenic injection of CT26 cells offers a clinically relevant murine model for metastatic colorectal cancer and will facilitate evaluation of RNAi therapeutic targets against metastatic cancer. This model will also be useful in the assessment of the effects of RNAi on the tumor microenvironment and possible toxicity to normal host cells. Furthermore, this model may predict the clinical course and the ultimate in vivo response to RNAi therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 471.
Abstract 4713: Serum thyroglobulin, a biomarker for iodine deficiency, and risk of upper gastrointestinal cancers
Authors: Lin Shih-Wen , Fan Jin-Hu , Dawsey Sanford M. , Sun Xiu-Di , Taylor Philip R. , Qiao You-Lin , Abnet Christian C. 
Published: February 2011

Abstract
Objectives: Gastric cancer is the second leading cause of cancer death worldwide and has been hypothesized to be associated with iodine deficiency. While iodine concentrations are highest in the thyroid, iodine also concentrates in gastric tissue where it may act as an antioxidant for the stomach and possibly the esophagus. We previously showed that self-reported goiter was associated with significantly increased risk of gastric noncardia adenocarcinoma (GNCA) and non-significantly increased risks of gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC). Iodine deficiency is correlated with increased serum thyroglobulin, and this study aimed to determine whether serum thyroglobulin is associated with GNCA, GCA, and ESCC in a Chinese population with very high rates of upper gastrointestinal (UGI) cancers.
Methods: We examined the association between serum thyroglobulin levels and the three UGI cancers in a study nested in the Linxian General Population Nutrition Intervention Trial. At baseline, blood was drawn from participants, ages 40-69 years, and outcomes were identified during 15 years of follow-up. Approximately 200 subjects of each case type and 400 non-case controls were selected for serum thyroglobulin concentration measurements. All samples were first screened for thyroglobulin antibody, and thyroglobulin concentrations were then measured by radioimmunoassay (RIA) for thyroglobulin-antibody-positive samples or by immunometric assay (IMA) for thyroglobulin-antibody-negative samples. Thyroglobulin concentrations were analyzed as quartiles using logistic regression models adjusted for numerous potentially confounding factors.
Results: 25% of females and 5% of males in the controls were thyroglobulin-antibody-positive. Compared to participants in the lowest quartile, those in the highest quartile of serum thyroglobulin had adjusted odds ratios of 0.82 (95% confidence interval 0.50-1.36) for GNCA, 1.12 (0.66-1.90) for GCA, and 0.73 (0.44-1.21) for ESCC.
Conclusions: Using serum thyroglobulin, a sensitive biomarker of iodine deficiency, we found no association between serum thyroglobulin concentrations and risk of UGI cancer in the overall study population. Our results do not support the hypothesis that iodine deficiency is associated with an increased risk of UGI cancers in this population.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4713.
Abstract 4714: Oral human papillomavirus infection among HIV infected and uninfected men who have sex with men
Authors: Beachler Daniel C. , Jacobson Lisa P. , Margolick Joseph B. , Gillsion Maura L. , D'Souza Gypsyamber 
Published: February 2011

Abstract
Introduction: Human papillomavirus (HPV) causes a subset of oropharyngeal cancers but the prevalence and risk factors for oral HPV infection are not well understood. Initial studies suggest HIV-infected individuals have an increased incidence of HPV-related cancers including oropharyngeal cancer.
Methods: Oral exfoliated cells were collected using a swish and gargle with 10ml of Scope mouthwash in 149 HIV-infected and HIV-uninfected men who have sex with men (MSM) in the Baltimore center of the MACS. Samples were tested for 37 types of HPV DNA using PGMY09/11 consensus primers and line blot hybridization. Logistic regression was used to explore risk factors for infection.
Results: Prevalent oral HPV infection was common among the 62 HIV-infected and the 87 HIV-uninfected MSM (39% vs 28%, p=0.15). HPV16 was the most common HPV type detected and was found in an alarming 13% of MSM (8.2% of HIV-infected and 16% of HIV-uninfected MSM, p=0.15). The most common other oncogenic oral HPV infections detected were HPV 66, 68, 83 (2.0% prevalence each), and 45, 53, 58, 59, 73 (1.3% each). In this study 32% of men reported multiple oral sex partners in the past six months. Oral HPV16 prevalence was significantly associated with number of recent oral sexual partners among HIV uninfected (p-trend=0.04) but not HIV infected participants. The majority of HIV-infected participants were currently on HAART (74%), had CD4 cell count&gt;500 (65%) and HIV viral load &lt;500 copies/ml (78%). Oral HPV prevalence was similar among current HAART users (41%) compared to former or never HAART users (27% and 40% respectively) and prevalence increased non-significantly with low CD4 and high HIV viral load. In multivariate analysis of HIV infected but not HIV-uninfected MSM, current marijuana users were over ten times more likely (OR=11.5 95%CI=1.5-17) to have prevalent high risk HPV infection.
Conclusions: Oral HPV16 prevalence is high among both HIV uninfected and HIV infected MSM suggesting they may be at increased risk for HPV-associated oropharyngeal cancers. Oral HPV risk factor profiles differed by HIV status. Oral HPV prevalence was similar among HIV infected HAART users and non-users suggesting HAART may not improve oral HPV clearance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4714.
Abstract 4717: A search for overlapping HLA risk loci between NHL and autoimmune diseases
Authors: Conde Lucia , Bracci Paige M. , Smith Martin T. , Akers Nicholas K. , Riby Jacques , Agana Luz , Holly Elizabeth A. , Halperin Eran , Skibola Christine F. 
Published: February 2011

Abstract
Non-Hodgkin lymphoma (NHL) is a group of B- and T-cell neoplasms originating primarily from the lymph nodes, and represents the most common hematological malignancy in the United States. We recently conducted a genome-wide association study (GWAS) using DNA pools and identified a new risk locus for follicular lymphoma (FL) in the Class 1 human leukocyte antigen (HLA) region on chromosome 6. Currently, we are following up these results in a second GWAS using a subset of 757 NHL cases and 811 controls from a larger case-control study of NHL based in the San Francisco Bay Area using the Illumina HumanCNV370-Duo BeadChip. In the preliminary scan, we found additional evidence of Class 1 HLA loci that influence FL susceptibility, as well as loci in the Class 2 region, suggesting the importance of HLA genetic variation in FL risk. There is also clear evidence that HLA Class 1 and Class 2 loci confer genetic susceptibility to autoimmune diseases such as Crohn's disease (CD), type 1 diabetes (T1D), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Thus, because a history of autoimmune disease may increase risk of NHL, we explored whether HLA-region risk loci are common between these autoimmune diseases and NHL.
Using genetic data available from the Wellcome Trust Case-Control Consortium (WTCCC) for CD and the software package BEAGLE 3.0.3, we imputed SNPs to look for association signals in the HLA region. SNPs were imputed based on CD genotyped SNPs and haplotype information from unrelated CEU samples in the HapMap phase II data. A Cochran-Armitage test for an additive genetic effect implemented in PLINK v1.05 was subsequently performed to test the genotype-phenotype associations of genotyped and imputed SNPs. Our preliminary results suggest associations in the HLA Class 2 region near the HLA-DQA2 and HLA-DQB2 genes, providing evidence that overlapping risk loci may exist between FL and CD. We are currently expanding our analysis to include genetic data for other autoimmune diseases available from WTCCC such as T1D and RA. These analyses will contribute new data about genetic variation in plausible HLA region pathways and will help to identify potentially functional genetic factors that contribute to lymphoma susceptibility.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4717.
Abstract 4725: Interrogating region 4 of 8q24.13 for prostate cancer risk in African Americans
Authors: Hernandez Wenndy , Benn-Torres Jada , Hooker Stanley E. , Robbins Christiane , Carpten John , Kittles Rick A. 
Published: February 2011

Abstract
In the USA, African American (AA) men are at higher risk of developing and dying from prostate cancer (Pca). Strong and replicable associations between prostate cancer risk and regions 1, 2, and 3 of 8q24 among cohorts of European ancestry have been found but few for those of African ancestry. Recently, we discovered in a study of AAs, a fourth region of Pca risk at 126 Mb of 8q24.13 surrounding SNP rs7008482. Region 4 is 2 Mb upstream of the other three regions on 8q24 and contains two interesting candidate genes for Pca risk. To further interrogate region 4, we performed fine-mapping within a 500-Kb region (126.1Mb-126.6Mb). SNPs were selected for fine-mapping of the region based on the following characteristics: tagging SNPs from Yoruba HAPMAP data and non-synonymous or potential regulatory SNPs. We genotyped 250 SNPs in 263 AA Pca cases and 562 AA healthy controls. A structured-association analysis taking into account African ancestry, (local 8q24 ancestry and genomic ancestry) revealed that several SNPs within two genes KIAA0196 and NSMCE2 were significantly associated with Pca risk. The majority of the associated SNPs were common and exhibited low to moderate risk which may contribute to high population attributable risk in African Americans. Among these, rs16900305, located in an intronic region of KIAA0196, exhibited the strongest association (P=0.0003). KIAA0196 has been shown to be over-expressed in clinical prostate carcinomas and in approximately 30% of hormone-refractory tumors. Our findings strongly support region 4 in 8q24.13 as a candidate locus influencing prostate cancer risk among African Americans. Given the two interesting genes in this region and strong associations in a high risk group for Pca, further attention to this region is warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4725.
Abstract 4726: Prostate cancer risk profiles based on 24 single nucleotide polymorphisms, age, and family history
Authors: Kraft Peter , Lindstrom Sara ,   Breast and Prostate Cancer Cohort Consortium
Published: February 2011

Abstract
Genome-wide association studies (GWAS) have identified over two dozen loci associated with risk of prostate cancer in men of European ancestry. Although much work remains to be done to identify the causal alleles at these loci and understand their function, the current set of GWAS-identified marker alleles could be used to predict individualized risks of prostate cancer diagnosis, which might then be used to inform individuals’ screening and treatment choices. However, despite initial optimism about their clinical utility, genetic risk profiles for prostate cancer have had low discriminatory and predictive power.
We evaluated the performance of various risk models based on an expanded set of 24 SNPs known to alter prostate cancer risk in 9,109 prostate cancer cases and 9,045 matched controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). As we found no evidence of pairwise gene-gene interactions, we considered two models for the log odds of disease which assume additivity across loci: a simple sum of risk alleles carried and a step function by deciles of the weighted allele sum.
Using the allele sum model, the area under the ROC curve (AUC) was 0.598. Adding information about family history increased this estimate to 0.612. We observed no difference in AUC estimates when stratifying for age of onset (AUCs: ≤60 years: 0.603, 60-70 years: 0.604, 70-80 years: 0.593, &gt;80 years: 0.552).
Per-allele increases in the odds of diagnosis with stage C or D cancer were similar to those for stages A and B (p=0.96), but the multiplicative increase in odds for high grade cancer (Gleason &gt; 7) for each risk allele was attenuated by a factor of 0.97 relative to low grade cancer (p=0.03). We observed no interaction between family history of prostate cancer and number of risk alleles carried (P=0.83)
Compared to the 10th percentile, men in the highest 90th percentile are at a 3.6-fold risk (95% CI: 3.2-4.2) of developing prostate cancer assuming an allele sum model and at a 3.8-fold risk (95% CI: 3.3-4.3) assuming a weighted allele sum model.
These scores can be used to estimate absolute risks of prostate cancer. For example, the risk that a 40-year old European-ancestry man in the highest decile of genetic risk and a family history of prostate cancer will be diagnosed with prostate cancer by age 50 0.67%, or about 2.5 times the average. These risks could be used by individual men when weighing the benefits and risks of prostate cancer screening, although we caution that our predicted risks require external calibration.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4726.
Abstract 4728: Genome-wide analysis of genetic alterations in seminoma using high resolution single Nucleotide polymorphism (SNP) arrays
Authors: LeBron Cynthia , Pal Prodipto , Brait Mariana , Dasgupta Santanu , Looijenga Leendert HJ , Netto George , Sidransky David , Hoque Mohammad 
Published: February 2011

Abstract
Testicular germ cell tumors (TGCT's) represent the most common malignancy among young males between the ages 15-40 years. Many genomic alterations have been observed in testicular cancer, however very few of these alterations have been associated with deregulation of gene function. The impact of CNVs on cancer susceptibility and tumor progression is only recently been explored in different cancer types. To our knowledge no comprehensive studies of testicular cancer using high-resolution SNP array have been performed, partially due to the rarity of this disease and low resolution of previous cytogenetic techniques. To identify new genomic alterations we performed a genome-wide analysis of copy-number changes and loss of heterozygosity (LOH) in 24 seminomas and validated our findings by a complementary approach. We have also confirmed the several previously reported genomic alterations in seminoma and discovered eight novel genomic alterations including amplifications and homozygous deletions. Moreover, a comparison of genomic alterations of early stage and late stage identified CNV that correlate with progression which included deletions in chromosome 4q, 5p, 9q, 13q and 20p and amplifications in chromosomes 9q and 13q. CNV aberrations for candidate genes within selected regions these regions were further validated using quantitative PCR (QPCR). 40-75% correlation was observed between CNV by SNP analysis and QPCR. In conclusion, SNP microarrays are a valuable tool to measure and identify genomic alterations in seminoma, and we identified several genomic alterations, which may help pinpoint cancer causing genes and strengthen our understanding the biology of seminoma.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4728.
Abstract 4732: Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex-hormone binding globulin
Authors: Chu Lisa W. , Meyer Tamra E. , Li Qizhai , Menashe Idan , Yu Kai , Rosenberg Philip S. , Huang Wen-Yi , Quraishi Sabah , Kaaks Rudolf , Weiss Jocelyn M. , Hayes Richard B. , Chanock Stephen J. , Hsing Ann W. 
Published: February 2011

Abstract
Multiple genome-wide association studies have identified several independent non-coding regions in chromosome 8q24 associated with risk for cancers of the prostate, breast, colon, and bladder. To explore their biological basis, we investigated the possible association between 164 single nucleotide polymorphism (SNPs) in the 8q24 risk regions, spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, and 3αdiol G) and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Age-adjusted linear regression using SNPs in an additive genetic model showed that three adjacent SNPs centromeric to prostate cancer risk region 2 (rs12334903, rs1456310, and rs980171) were associated with measured total testosterone (P&lt;1.1×10−3) and calculated bioavailable testosterone (P&lt;6.3×10−4). Suggestive associations were seen for a cluster of 9 SNPs in prostate cancer risk region 1 and androstenedione (P&lt;0.05). These preliminary findings, although in need of confirmation in larger studies, suggest that genetic variations in the 8q24 cancer risk regions may correlate with androgen levels, which in turn may provide some clues for the strong link between 8q24 and prostate cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4732.
Abstract 4736: Pleiotropic effect of 5p and 8q chromosome regions: Analyses on the TURIN EPIC cohort
Authors: Ricceri Fulvio , Guarrera Simonetta , Sacerdote Carlotta , Polidoro Silvia , Allione Alessandra , Rosa Fabio , Veldhoven Karin Van , Vineis Paolo , Matullo Giuseppe 
Published: February 2011

Abstract
BACKGROUND
Common sequence variants in 8q24 and 5p15 chromosomal regions have recently been associated with several cancer types and other pathologies. Notably, for most of them a strong environmental risk component has been described.
The aim of this study is to investigate for the first time in a cohort study the association among SNPs in those regions and several diseases.
METHODS
We conducted the study on Turin EPIC (European Perspective Investigation in Cancer and Nutrition) cohort: 10,604 volunteers recruited from 1993 to 1998, aged 35 to 64 years old. Each subject compiled a detailed questionnaire on life style and diet, provided a blood sample and was followed-up for life status, cancer, cardiovascular and diabetes incidence.
We selected from literature two SNPs in 5p15 region (rs401681, rs2736098) and five SNPs in 8q24 region (rs672888, rs1447295, rs9642880, rs16901979, rs6983267) which proved to be associated with several diseases in previous studies.
We calculated Hazard Ratios for each cancer site and cause of mortality under different genetic models, and incident diabetes Odd Ratios.
RESULTS
We observed 830 incident cancers (737 excluding skin carcinomas) and 342 overall death in the cohort since 1993.
Considering all cancers together, we observed a statistically significant increase in risk when the variant allele in SNP rs6983267 was present (HR 1.19, p&lt;0.01, per allele model); this increase is higher in men (HR 1.35, p&lt;0.001, per allele model).
We also found statistically significant associations among SNPs in 8q24 region and cancers of head and neck, colon-rectum, liver, lung, prostate, bladder, brain, thyroid, lymphomas, all cancers together and diabetes. We also observed statistically significant results for 5p15 region and melanoma.
CONCLUSIONS
Our analyses confirm for the first time in a cohort study the hypothesis of a pleiotropic effect on several disease susceptibility of 8q24 and 5p15 regions. We are also investigating if those associations are mediated by individual risk factors (diet, body mass index, smoking and blood pressure).
Further functional analyses are needed to better elucidate the mechanisms underlying the risk increase conferred by genetic variation in 8q24 and 5p15 regions.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4736.