bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4837: Joint effect of arsenic exposure and vascular endothelial growth factor polymorphisms on urothelial carcinoma risk.
Authors: Wang Yuan-Hung , Wu Chia-Chang , Chen Kuan-Chou , Chen Hsin-An , Huang Ming-Te , Wu Chih-Hsiung , Chiou Hung-Yi 
Published: August 2014

Abstract
Arsenic exposure is a major environmental risk factor for Urothelial carcinoma (UC) which includes cancers of bladder, renal pelvis and ureter (upper urinary tract). Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis which plays a critical role in various malignancies including UC. The aim of this study is to investigate the joint effect of arsenic exposure and VEGF polymorphisms on UC risk. A hospital-based case-control study consisted of 730 histologically confirmed UC cases and 850 age-matched cancer-free controls were recruited from September 1998 to December 2009. Polymorphisms in VEGF gene was determined by polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression. Subjects with high arsenic exposure had significantly increased risks of 2.4 and 2.5 for bladder cancer and upper urinary tract UC (UUTUC), respectively. A significantly higher UUTUC risk of 1.7 was found in those with one or more risk genotypes of VEGF gene. Individuals with high arsenic exposure who carried one or more risk genotypes of VEGF gene had significantly increased risks of 2.9 (95% CI=1.8-4.7) and 4.2 (95% CI=2.3-7.7) for bladder cancer and UUTUC, respectively. The UUTUC cases with high arsenic exposure carrying one or more risk genotypes of VEGF gene had a higher risk of advanced tumor stage. Our findings suggest that the joint effect of arsenic exposure and risk genotypes of VEGF gene is relatively predominant in UUTUC than in bladder cancer. Keywords: Arsenic, Bladder cancer, Upper urinary tract, Urothelial carcinoma, Vascular endothelial growth factor
Citation Format: Yuan-Hung Wang, Chia-Chang Wu, Kuan-Chou Chen, Hsin-An Chen, Ming-Te Huang, Chih-Hsiung Wu, Hung-Yi Chiou. Joint effect of arsenic exposure and vascular endothelial growth factor polymorphisms on urothelial carcinoma risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4837. doi:10.1158/1538-7445.AM2013-4837
Abstract 4838: Exploration of genome-wide two-locus SNP-SNP interactions relate to nasopharyngeal carcinoma susceptibility.
Authors: Su Wen-Hui , Chang Kai-Ping , Shugart Yin Yao , Chang Yu-Sun 
Published: August 2014

Abstract
Most of the genome-wide association studies (GWAS) are concentrated on the detection main effects and can only explain only a small fraction of the genetic risk. One possible explanation might be the existence of interactions between loci. This effect might be missed in traditional GWAS analysis. Testing for SNP-SNP interaction within a single GWAS study can identify the stronger results that are revealed when genes interact. Here, we have completed the genome-wide two-locus SNP-SNP interaction analysis in nasopharyngeal carcinoma (NPC). We started with the NPC GWAS dataset as our Discovery dataset, then we performed an exhaustive genome-wide two-locus search by pairing each SNP sets according to chromosome positions for PLINK epistasis analysis. The analysises were also performed within each SNP sets to ensure every SNP has performed epistasis analysis with all the other SNPs in the dataset. In total, there were 4,244,943 unique interactions after the genome-wide two-locus epistasis analysis. The top 10,000 interaction pairs from the Discovery dataset were selected for validation test in a subset of independent samples. Finally, 67 SNP pairs remain significant in Validation and Combined analysis and can successfully passed permutation tests for 10,000 times. The 67 significant interaction pairs can be clustered into 39 interaction groups which 12 (32%) of the 39 clusters were with at least two nearby SNPs from one of the interaction chromosome. This study represents one of the first attempts to explore the high-dimensional genetic architecture of NPC on a genome-wide scale.
Citation Format: Wen-Hui Su, Kai-Ping Chang, Yin Yao Shugart, Yu-Sun Chang. Exploration of genome-wide two-locus SNP-SNP interactions relate to nasopharyngeal carcinoma susceptibility. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4838. doi:10.1158/1538-7445.AM2013-4838
Abstract 4842: Hazard ratio for colorectal cancer risk in Lynch syndrome is inversely associated with age.
Authors: Jenkins Mark A. , Win Aung Ko , Dowty James G. , Mathews John D. , Hopper John L. 
Published: August 2014

Abstract
Introduction: Carriers of germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) have a high risk of colorectal and other cancers (Lynch syndrome). Between 30% and 70% of carriers will be develop colorectal cancer by age 70 if they are not screened for the disease. What is not well understood is how the effect of mutations, in absolute and relative terms, varies by age.
Methods: We conducted a literature review to identify studies of colorectal cancer that estimated age-specific hazard ratios for colorectal cancer for carriers of a mutation in MLH1 or MSH2 compared with the general population. Studies were excluded if they did not adjust correctly for ascertainment. We conducted a random effects meta-analysis to estimate the average age-specific hazard ratio. Annual risk (incidence) by multiplying the population incidence by the age-specific hazard ratio estimated by the meta-analysis.
Results: We identified six studies comprising 673 families (282 MLH1, 391 MSH2). All studies observed that the hazard ratio for colorectal cancer was highest at young ages and decreased with age. This pattern was observed for both males and females and for both MLH1 and MSH2 mutation carriers. Overall, the hazard ratio dropped 6-8 fold over three decades (Table). Incidence of colorectal cancer for carriers increased until age 40 years for males and 50 years for females, and then plateaued (Table).
Conclusion: At younger ages, in multiplicative terms, the magnitude of the increased risk conferred by the mutations is substantially greater than at older ages. The reason for this age-dependency is not known. It is, however, consistent with a multi-stage model of carcinogenesis for Lynch syndrome. These findings add to the complement of factors that complicate risk estimation for Lynch syndrome including: polygenic effects, non-genetic risk modifiers, and the possibility of a parent-of-origin effect. There is still much to learn about the clinical implications and carcinogenesis of Lynch syndrome.
Meta-analysis estimates of hazard ratios and incidences for colorectal cancer by age group. 30-39 year olds 40-49 year olds 50-59 year olds 60-69 year olds Hazard ratio (95%CI): Risk of colorectal cancer in carriers/risk for the general population. Males 120 (60-243) 95 (39-226) 33 (14-78) 14 (4.2-51) Females 80 (42-154) 70 (35-139) 28 (19-41) 14 (7.4-26) Incidence: Proportion of carriers diagnosed with colorectal cancer per year. Males 1 in 146 1 in 50 1 in 39 1 in 38 Females 1 in 490 1 in 135 1 in 69 1 in 61
Citation Format: Mark A. Jenkins, Aung Ko Win, James G. Dowty, John D. Mathews, John L. Hopper. Hazard ratio for colorectal cancer risk in Lynch syndrome is inversely associated with age. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4842. doi:10.1158/1538-7445.AM2013-4842
Abstract 4844: Polymorphisms in regulatory T cell related genes and ovarian cancer survival.
Authors: Charbonneau Bridget , Knutson Keith , Vierkant Robert A. , Cunningham Julie M. , Fogarty Zachary C. , Kalli Kimberly R. , Maurer Matthew J. , Oberg Ann L. , Fridley Brooke L. , Preston Claudia C. , Pharoah Paul D.P. , Ramus Susan J. , Phelan Catherine M. , Odunsi Kunle , Moysich Kirsten , Goode Ellen L. 
Published: August 2014

Abstract
Tumor infiltrating regulatory T cells (Tregs) appear to play a role in survival in a number of solid tumors, including ovarian cancer. We assessed genetic variation via tag SNPs (N=749) in 25 Treg associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. SNPs were selected based on r2 ≥ 0.8, MAF ≥ 0.05, 5 kb upstream and downstream from the gene. We had SNP and outcome data for ovarian cancer from 10,084 combined ovarian cancer cases, including 5,248 high grade serous, 1,452 endometrioid, 661 mucinous, and 795 clear cell cases of European descent across multiple studies from the Ovarian Cancer Association Consortium (OCAC). Cox proportional hazards regression modeling was used to estimate per-allele hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with overall survival, adjusting for age at diagnosis, population substructure PCs, study site, histology (for the all case analysis), tumor stage, tumor grade and oral contraceptive use. The strongest associations were found for endometrioid histologic subtype and IL2RA SNPs (maximum r2=0.67) rs11256497 [HR=1.42, 95% CI: 1.22-1.64; p=5.7 x 10−6], rs791587 [HR=1.36, 95% CI: 1.17-1.57; p=6.2 x 10−5], rs2476491 [HR=1.40, 95% CI: 1.19-1.64; p=5.6 x 10−5], and rs10795763 [HR=1.35, 95% CI: 1.17-1.57; p=7.9 x 10−5], as well as clear cell ovarian cancer and CTLA4 SNP rs231775 [HR=0.67, 95% CI: 0.54-0.82; p=9.3 x 10−5]. No other associations were observed at p&lt;1 x 10−4. Overall, this study provided evidence that variation in genes related to Tregs, particularly IL2RA and CTLA4, influence ovarian cancer survival.
Citation Format: Bridget Charbonneau, Keith Knutson, Robert A. Vierkant, Julie M. Cunningham, Zachary C. Fogarty, Kimberly R. Kalli, Matthew J. Maurer, Ann L. Oberg, Brooke L. Fridley, Claudia C. Preston, Paul D.P. Pharoah, Susan J. Ramus, Catherine M. Phelan, Kunle Odunsi, Kirsten Moysich, Ellen L. Goode. Polymorphisms in regulatory T cell related genes and ovarian cancer survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4844. doi:10.1158/1538-7445.AM2013-4844
Abstract 4846: Genetic variants in the Wnt/beta-catenin signaling pathway as indicators of ovarian cancer risk and survival.
Authors: Pierzynski Jeanne A. , Hildebrandt Michelle AT , Wu Xifeng , Lu Karen H. , Liang Dong 
Published: August 2014

Abstract
Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer death in 2012. Much is known about the correlation between BRCA mutations and ovarian cancer, but less is known about the impact of common, germline genetic variants on ovarian cancer risk and clinical outcomes. The Wnt/beta-catenin pathway has major roles in regulation of stem cells and other cellular pathways and has been shown to be involved in the development of several different cancers. Therefore, we examined 434 Single Nucleotide Polymorphisms (SNPs) in the Wnt/beta-catenin pathway in 339 ovarian cancer cases and 349 controls. These variants were then assessed for association with risk and clinical outcomes of ovarian cancer. Sixteen polymorphisms had a statistically significant association with ovarian cancer risk with the most significant association being for rs11668593 in APC2 under the dominant model [odds ratio (OR)=0.61; 95% confidence interval (CI), 0.44-0.83]. Unfavorable analysis showed a highly significant cumulative effect of these 16 SNPs on risk (P for trend = 4.22x10−15). In the clinical outcomes analysis, there were eight SNPs that showed an association with ovarian cancer survival. The most significant association with survival was seen for rs11054760 in LRP6 [OR=2.16; 95% CI, 1.33-3.50] which resulted in a poorer survival in patients carrying the heterozygous or homozygous variant genotypes compared to those with the homozygous common genotype. Individuals with the common genotype for rs11054760 had a longer median survival time of 52.7 months compared to only 25.9 months for those with variant containing genotypes (Plog-rank = 3.54x10−4). A gene-dosage effect with a decrease in survival as the number of unfavorable genotypes increased was evident (P for trend = 4.57x10−9). These results implicate genetic variation in the Wnt/beta-catenin signaling pathway as having an impact on risk and clinical outcomes of ovarian cancer.
Citation Format: Jeanne A. Pierzynski, Michelle AT Hildebrandt, Xifeng Wu, Karen H. Lu, Dong Liang. Genetic variants in the Wnt/beta-catenin signaling pathway as indicators of ovarian cancer risk and survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4846. doi:10.1158/1538-7445.AM2013-4846
Abstract 4853: Comparison of automated and a semi-automated methods for assessing Ki-67 staining.
Authors: Ondracek Rochelle P. , Marshall James , Kasza Karin , Morrison Christopher , Ghajar Simoya , Morrison Carl , Mehedint Diana , Mohler James L. 
Published: August 2014

Abstract
Human evaluation of immuno-staining is limited by the subjectivity of the human evaluator, is time-consuming and is expensive. Semi-automated means of tissue evaluation have been proposed, but most of these have large subjective components. This study assesses semi-automated and newly-developed fully automated methods of evaluating Ki-67 staining of benign and malignant tissue from radical prostatectomy specimens. A research tissue microarray was constructed from 68 prostatectomy specimens and contained 3 core samples of benign and 3 of malignant tissue from each research subject. Tissue microarray sections were immune-stained for Ki-67. Two technicians (SG & CM) evaluated each TMA core and labeled the nuclei positive for Ki-67 with a green dot, and negative with a red dot. Images were collected and Image-Pro software was used to count the number of green and red dots. In a separate procedure, Image-Pro (IP) software was used to identify nuclei, and grade each nucleus as positive or negative, and the percentage of positive nuclei was calculated.
The semi-automated results correlated with each other (0.58, P&lt;0.001). The semi-automated and fully automated results also correlated (0.8, P&lt;0.001, CM vs. IP and 0.59, P&lt;0.001, SG vs. IP). When stratified by tissue type (benign vs. malignant), the semi-automated results and the fully-automated results also correlated (benign tissue: 0.68, P&lt;0.001, CM vs. IP, and 0.80, P&lt;0.001, SG vs. IP; tumor tissue: 0.89, P&lt;0.001, CM vs. IP and 0.47, P&lt;0.001, SG vs. IP).
These results suggest that semi-automated and automated analysis of Ki-67 staining of prostate tissue produces comparable results, and automated analysis can be used for prostate cancer research.
Citation Format: Rochelle P. Ondracek, James Marshall, Karin Kasza, Christopher Morrison, Simoya Ghajar, Carl Morrison, Diana Mehedint, James L. Mohler. Comparison of automated and a semi-automated methods for assessing Ki-67 staining. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4853. doi:10.1158/1538-7445.AM2013-4853
Abstract 4860: Chemopreventive effects of α-santalol on ultraviolet B induced skin tumorigenesis by modulating cell cycle regulators.
Authors: Santha Sreevidya , Dwivedi Chandradhar 
Published: August 2014

Abstract
Previous studies from our laboratory have shown chemopreventive effects of 5% α-santalol, a sequiterpene isolated from the sandalwood oil in ultraviolet-B induced skin tumor multiplicity in SKH-1 hairless mice. However, this dosage did not have significant effect on tumor incidence. The objective of this study was to investigate the effects of α-santalol (10%, w/v in acetone) on UVB-induced skin tumor incidence in SKH-1 hairless mouse model and to identify the molecular targets in α-santalol mediated protection. Tumor initiation and promotion were carried out by UVB radiation (30 mJ/cm2/day for 5 days a week up to 30 week) that is in the range of human exposure to sunlight that can cause skin cancer. Topical treatment of mice with α-santalol causes a significant reduction in tumor multiplicity, tumor volume and tumor incidence, and also delayed tumor development. Histopathological analysis of hematoxylin-eosin stained skin sections showed that α-santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and total thickness of the epidermis. The proliferation potential of skin and tumor tissue sections from UVB-induced carcinogenesis protocol was evaluated by immunohistochemical expression of proliferation marker PCNA. Both intensity of brown staining as well as the number of positively stained nuclei were reduced in skin tumors and adjacent skin tissues from α-santalol treated group when compared to control group. Western blot analysis of skin lysates showed that α-santalol decreases the level of different cyclin-dependent kinases and associated cyclins, Cdc25 phosphatases (Cdc25B and Cdc25C) together with an up-regulation of CDK inhibitor Cip1/p21. However, the level of Kip1/p27 and p53 did not show a significant difference. Our data suggested that α-santalol (10%, topical) is a safer and promising skin cancer chemopreventive agent through targeting different cell cycle regulators. (This work is supported by a Translational Cancer Center Research Grant, funded by the State of South Dakota).
Citation Format: Sreevidya Santha, Chandradhar Dwivedi. Chemopreventive effects of α-santalol on ultraviolet B induced skin tumorigenesis by modulating cell cycle regulators. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4860. doi:10.1158/1538-7445.AM2013-4860
Abstract 4862: Cancer chemopreventive potential of grape seeds and skin in mice inoculated with Ehrlich ascites carcinoma cells.
Authors: Badr El-Din Nariman K. , Ali Doaa A. , Abou-El-Magd Rania F. , Soliman Nahed A. 
Published: August 2014

Abstract
Chemoprevention by dietary constituents holds great promise to control cancer. Grape seeds(GSE) and skin (GSK) contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. This study was undertaken to investigate the chemopreventive effects of GSE and GSK efficacies and associated mechanisms on tumor growth in mice. GSE & GSK were separated from the pulp of grape Vitis vinifera, dried and ground to powder. Equal amounts of GSE & GSK were mixed uniformly with the standard diet powder at concentrations of 10% (w/w). The supplemented diet was started two weeks before tumor cells inoculation and continued until the end of the experiment. Female Swiss albino mice were inoculated subcutaneously with 2.5x106
Ehrlich ascites carcinoma (EAC) cells. Tumor growth was monitored for 30 days.Cell cycle progression was measured and the apoptotic effect of GSE and GSK on tumor cells were evaluated by flow cytometric analysis, histopathology and transmission electron microscopy examination. GSE & GSK intake prevented tumor development in 47% of the animals.
Tumor volume and tumor weight measured at the termination of the experiment were reduced by 93.9 %& 86.3 %, p&lt; 0.001) respectively as compared to the untreated tumor- bearing mice. GSE& GSK induced a marked increase in the percentage of apoptotic tumor cells as determined by flow cytometric analysis and confirmed by histopathological and electron microscopy examination. These changes were associated with significant
G1-phase cell cycle arrest, decrease in the expression of Bcl-2, increase of the expression of p53 and induced caspase-3 activation in the tumor cells. Our data demonstrated that grape seeds& skin intake resulted in profound cell growth inhibition by a mechanism involved G1-phase cell cycle arrest, and apoptosis. Therefore, dietary grape seeds and grape skin possess cancer chemopreventive potential and provide support for their use in human cancer chemoprevention.
Citation Format: Nariman K. Badr El-Din, Doaa A. Ali, Rania F. Abou-El-Magd, Nahed A. Soliman. Cancer chemopreventive potential of grape seeds and skin in mice inoculated with Ehrlich ascites carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4862. doi:10.1158/1538-7445.AM2013-4862