bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1277: Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with obesity and lifestyle factors on postmenopausal breast cancer risk
Authors: Jung Su Yon , Ho Gloria , Rohan Thomas , Strickler Howard , Bea Jennifer , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng , Crandall Carolyn 
Published: July 2017

Abstract
Objectives: Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. Stratifying via obesity and lifestyle modifiers, we evaluated the effects of insulin-like growth factor-I (IGF-I)/insulin resistance (IR)–related traits on breast cancer risk as a mediator or influencing factor in this case-cohort study.
Method: Using 75 single-nucleotide polymorphisms (SNPs) in genes related to IGF-I/IR traits and signaling pathways, and data from 1,003 postmenopausal women in Women’s Health Initiative Observation ancillary studies, we assessed the effects of IGF-I/IR-traits (fasting total and free IGF-I, IGF binding protein-3, glucose, insulin, and homeostatic model assessment–insulin resistance) by proportional change estimation. Using traits as mediators of the IGF-I/IR–traits genetic variants-cancer relationship, we partitioned total effect of these genetic variants on cancer risk into two putative mechanisms: 1) indirect (mediated by traits) and 2) direct (through pathways other than traits). For the effects of IGF-I/IR traits on IGF-I/IR signaling pathways–relevant genetic variants–cancer risk, we used the same algorithm as that for mediator, but interpreted as an influential factor.
Results: Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E nonusers and users. The mediation effects of IGF-I/IR traits on these SNPs–cancer relationship differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by IGF-I/IR traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways–related genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP–cancer relationship explained by IGF-I/IR traits varied 45-50% between the strata.
Conclusions: Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits.
Citation Format: Su Yon Jung, Gloria Ho, Thomas Rohan, Howard Strickler, Jennifer Bea, Jeanette Papp, Eric Sobel, Zuo-Feng Zhang, Carolyn Crandall. Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with obesity and lifestyle factors on postmenopausal breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1277. doi:10.1158/1538-7445.AM2017-1277
Abstract 1279: A polymorphism of VEGF -2489C/T is associated with prostate cancer susceptibility in Mexicans
Authors: Martínez-Rizo Abril , Casillas-Rangel Xavi ,   Cuerpo Académico Investigación Bioquímica (UAN-CA-266), Andrade-Madrid Hilda , Benites-Godinez Veronica , Rodríguez-Ocampo Nallhely 
Published: July 2017

Abstract
Introduction: Prostate cancer (CaP) encompasses a range of malignant prostate tissue dysplasias that primarily affects men over 50 years, is the second leading cause of cancer mortality in males. VEGF expression is associated with tumor progression and metastasis in patients with CaP. The SNP -1154 G/A is associated with the severity of CaP populations in Tunisia and the United Kingdom while -634 G/C alone has been associated in Tunisian population. It is unknown whether these polymorphisms could serve as biomarkers in the Mexican population.
Aim: To associate VEGF polymorphisms -1154 G/A and - 634 G/C with the severity of prostate cancer in patients of western Mexico.
Materials and methods: The gDNA was analyzed a total of 525 men of whom 301 are presented HBP and 224 patients with clinical diagnosis of prostate cancer. For association with severity they were subclassified into high (≥7) and low grade (≤6) following the Gleason scale. Genotyping was performed by Real Time PCR using TaqMan probes system.
Results. When we compare the allelic frequencies in the control group, they are in Hardy-Weinberg equilibrium. However, no significant association of the disease with polymorphisms or severity or progression was found.
Conclusions: There is no association between prostate cancer and genetic polymorphisms at -634 and -1154 position of the promoter region of VEGF.
Note: This abstract was not presented at the meeting.
Citation Format: Abril Martínez-Rizo, Xavi Casillas-Rangel, Cuerpo Académico Investigación Bioquímica (UAN-CA-266), Hilda Andrade-Madrid, Veronica Benites-Godinez, Nallhely Rodríguez-Ocampo. A polymorphism of VEGF -2489C/T is associated with prostate cancer susceptibility in Mexicans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1279. doi:10.1158/1538-7445.AM2017-1279
Abstract 1293: ABO blood type and cancer risk: preliminary findings from a phenome analysis
Authors: Beeghly-Fadiel Alicia , Giri Ayush , Bastarache Lisa , Pulley Jill , Warner Jeremy , Denny Josh 
Published: July 2017

Abstract
Introduction: ABO blood type has long been implicated in disease susceptibility, including cancer. However, evidence for associations with many malignancies is mixed. We applied a novel phenome approach to test to cancer codes from electronic medical records (EMR) in relation to ABO blood type in a large predominantly Caucasian study population.
Approach: Among adults aged 18-100, cancer case and control status were assigned using 58 general neoplasm related phenome codes to de-identified EMR at the Vanderbilt University Medical Center. Blood type from serologic assays was ascertained from EMR-linked laboratory reports. Associations between blood type and cancer phenomes were quantified with Odds Ratios (OR) and corresponding 95% Confidence Intervals (CI) from logistic regression in models adjusted for sex and stratified by race/ethnicity. Only analyses with at least 100 cases per strata were conducted.
Results: Among 221,015 Non-Hispanic Caucasians, 37,841 Blacks, 7,714 Hispanic Caucasians, and 3,616 Asian subjects with ABO blood type available in linked EMR, we evaluated 56, 37, 4, and 3 general cancer phenome codes, respectively. After employing Bonferroni corrections, ABO blood type was significantly associated with cancers of the pancreas, ovary, cervix, skin, and hematopoietic system. Caucasians with blood type O were less likely to have ovarian cancer (OR: 0.82, 95% CI 0.73-0.91) and pancreatic cancer (OR: 0.83, 95% CI: 0.74-0.92), and more likely to have squamous cell or other skin cancer (OR: 1.08, 95% CI: 1.04-1.13) and myeloid leukemia (OR: 1.15, 95% CI: 1.06-1.25) than those with other blood types (A, B, or AB). Hispanic Caucasians with blood type O were less likely to have cervical cancer (OR: 0.56, 95% CI: 0.38-0.82) than those with other blood types. No associations surpassed correction for multiple comparisons among Blacks or Asians.
Conclusions: Our phenome approach confirmed known associations between blood type and risk of pancreatic and ovarian cancer, and adds to accumulating evidence supporting associations with skin cancer and leukemia. Our novel cervical cancer association among Hispanic Caucasians and other nominally significant findings, especially in understudied non-Caucasians, should be further evaluated in large and diverse populations. In addition, research to determine how ABO blood type may influence cancer development and progression, and if such associations can be exploited for risk prediction or cancer prevention is warranted.
Citation Format: Alicia Beeghly-Fadiel, Ayush Giri, Lisa Bastarache, Jill Pulley, Jeremy Warner, Josh Denny. ABO blood type and cancer risk: preliminary findings from a phenome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1293. doi:10.1158/1538-7445.AM2017-1293
Abstract 131: Chemotherapeutic effects of naturally occurring colossolactones against solid tumor cells in-vitro
Authors: Baghdadi Mohammed A. , Al-Abbasi Fahad A. , El-Halawany Ali M. , Al-Abd Ahmed M. 
Published: July 2017

Abstract
Colossolactones were isolated previously from the Vietnamese mushroom ganoderma colossum, such triterpenoids. The different colossolactone compounds (schisanalactonoe a, colossolactone I, ergosterol, colossolactone III, colossolactone II, colossolactone IV, colossolactone E) characterized by the presence of a six-membered lactone ring (ring D) with or without a seven-membered lactone rings (ring A) were isolated. In the current study, using DPPH free radical scavenging assay, all colossolactone compounds showed weak antioxidant activity with EC50’s of 99.46, 220.32, 219.65, 100.81, 238.54, 116.57 and 131.94 µM, respectively. Isolated compounds were examined for their potential anticancer activity against breast (MCF-7), cervix (HeLa), colorectal (HCT-116) and liver (HepG2) cancer cells. Cytotoxicity of the isolated compounds was assessed in the aforementioned cell lines using SRB assay after 72 h of exposure and fitted using Emax model. Amongst colossolactones, schisanalactonoe-A and colossolactone-IV showed the best cytotoxic profile in all cell lines under investigation with IC50’s ranged from 4.9 to 64.2 µM; and R-fraction less than 47.5%. Further mechanistic studies for the detailed mechanism of cytotoxicity of schisanalactonoe-A and colossolactone-IV are currently carried out.
Citation Format: Mohammed A. Baghdadi, Fahad A. Al-Abbasi, Ali M. El-Halawany, Ahmed M. Al-Abd. Chemotherapeutic effects of naturally occurring colossolactones against solid tumor cells in-vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 131. doi:10.1158/1538-7445.AM2017-131
Abstract 1311: Germline variation at 8q24 and prostate cancer risk
Authors: Wang Kan , Olama Ali Amin Al , Eeles Rosalind , Conti David , Kote-Jarai Zsofia , Haiman Christopher A. 
Published: July 2017

Abstract
The 8q24 region harbors multiple risk variants for distinct cancers including 7 for prostate cancer, the majority of which lie in separate linkage disequilbrium blocks. It is not known whether a common biological mechanism underlies the association of genetic variation with cancer risk at 8q24, or whether there are site-specific functions of regulatory elements that are affected in this region. Given the proximity, the MYC oncogene is a likely candidate as are multiple long non-coding RNAs in the region. To further understand the contribution of germline variation to prostate cancer risk we performed a comprehensive fine-mapping analysis of the region in men of European ancestry from the PRACTICAL/ELLIPSE Consortium. More specifically, we tested 1,731 genotype tag SNPs and 12,221 imputed variants spanning the risk region (127.3-129.0Mb) in 56,363 prostate cancer cases and 37,386 controls of European ancestry that were genotyped with the Illumina OncoArray. We performed stepwise logistic regression and identified 13 variants with risk allele frequencies between 0.006 and 0.998 that surpassed genome-wide statistical significance (p-values between 3.2x10-8 and 8.0 x10-78) and with per allele odds ratios ranging from 1.11(rs5013678) to 2.68(rs183373024). Ongoing analyses that will be presented include incorporating existing GWAS and fine-mapping data (iCOGs) for men of European and African ancestry (35,000 cases and 35,000 controls) using JAM, a Bayesian approach that investigates multi-SNP models using marginal meta-analysis statistics. Leveraging the power from the overall multiethnic meta-analysis (&gt;93,000 cases and &gt;72,000 controls) will provide further insight into the number of independent signals in the region and their contribution to prostate cancer risk in these populations.
Citation Format: Kan Wang, Ali Amin Al Olama, Rosalind Eeles, David Conti, Zsofia Kote-Jarai, Christopher A. Haiman. Germline variation at 8q24 and prostate cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1311. doi:10.1158/1538-7445.AM2017-1311
Abstract 1317: Simultaneous identification of candidate melanoma risk variants using massively parallel reporter assay
Authors: Choi Jiyeon , Zhang Tongwu , Kovacs Michael , Xu Mai , Lam Nghi , Colli Leandro , Brown Kevin 
Published: July 2017

Abstract
Recent melanoma Genome-Wide Association Study (GWAS) has identified 20 common susceptibility loci via meta-analysis of ~15,000 cutaneous malignant melanoma cases. While GWAS is extremely powerful in identifying genomic regions contributing to melanoma risk, teasing out functional variants and unraveling molecular mechanisms by which the risk is conferred presents a tremendous challenge due to limited resolution of genetic structure and lack of high-throughput assay system. To simultaneously identify functional risk variants from multiple GWAS loci, we employed recently developed Massively-Parallel Reporter Assays (MPRA). Based on the hypothesis that many GWAS functional variants regulate gene expression through transcriptional mechanism, we systematically examined allele-specific transcriptional activities of genetically indistinguishable candidate variants. Out of ~2,800 melanoma-associated variants (r2&gt;0.4, EUR) from 16 melanoma loci for which transcriptional mechanism could be applied, 835 variants were prioritized based on their relevance as melanocyte-/melanoma-specific cis-element represented by ENCODE annotation as open chromatin or putative promoter/enhancer histone marks in melanocytes and melanoma cell lines. Pooled oligoes of 145bp encompassing each variant with either melanoma risk or protective allele coupled with 10 different unique sequence tags were cloned into luciferase vectors and transfected to melanoma cell lines. Resulting expressed tag counts were subsequently determined using massively parallel sequencing. We were able to identify ~200 potentially functional variants displaying allelic transcriptional activity by combining transfections in a melanoma cell line and HEK293FT cell line. Top functional SNPs from melanoma GWAS loci were also shown as significant eQTL SNPs in human melanocytes including MX2 on chromosome 21. Overlaying MPRA functional SNPs with melanocyte eQTL SNPs further enabled isolation of a functional risk variant among several highly linked MX2 eQTL SNPs. The results from this analysis will greatly accelerate the identification of functional melanoma risk variants and further shed light on molecular mechanisms of genetic susceptibility of melanoma in population.
Citation Format: Jiyeon Choi, Tongwu Zhang, Michael Kovacs, Mai Xu, Nghi Lam, Leandro Colli, Kevin Brown. Simultaneous identification of candidate melanoma risk variants using massively parallel reporter assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1317. doi:10.1158/1538-7445.AM2017-1317
Abstract 132: African polyherbal formulation alleviates benzene-induced leukemia in Wistar rats
Authors: Akanni Olufemi E. , Faremi Ayodeji , Agboola Aminat O. , Akanni Adekemi R. , Bamisaye Oluseyi E. 
Published: July 2017

Abstract
Background: Chemotherapy and radiotherapy are effective cancer treatment options but they are accompanied by serious side effects. Therefore, more effective therapies are sorely needed. This study investigated the chemotherapeutic effects of a polyherbal formulation on benzene induced leukemia in Wistar rats. The polyherbal formulation is composed of fruits such as Orange, Lime, Lemon, Pineapple, Grape and Vegetables like; Pumpkin leave, Garden egg in honey medium.
Method: Leukemia was induced by injecting 0.2 ml of benzene solution intravenously through the tail at 48 h intervals for four weeks. Leukemia developed in 92% of rats within 2 to 4 weeks after the last benzene injection and further observed for leukemia development in appropriate rat groups. Leukemia burden was assessed using indicator parameters such as total leukocyte, red blood cell count, hematocrit, and hemoglobin concentration. Immunophenotyping enumeration of CD 19 expression also corroborated the leukemia assessment by providing specific cellular marker for differentiation of the developed leukemia type. Exactly 0.48 ml of the polyherbal formulation was administered orally by gavage using oral cannular once daily post leukemia induction for four weeks.
Results: Leukemia induction reflected in significant reduction in hematocrit, hemoglobin concentration, red cell count and a marked and a significant increase in leukocyte count and CD 19 expression over the control (p &lt; 0.05). There is significant difference between the leukemia group treated with polyherbal formulation and the leukemia positive control group untreated.
Conclusion: This study reveals profound chemotherapeutic activity of the polyherbal formulation against experimentally developed leukemia by reversing the induced leukemia in the positive control rat group, hence the ability of the polyherbal formulation in alleviating the cancer symptoms.
Table 1.Hematological parameters in polyherbal formulation treated leukemia bearing Wistar rats.Estimated parametersNegative control rats (Mean±SD)Leukemia Positive rats. (Mean±SD)Polyherbal formulation treated leukemic rats (Mean±SD)CD 19 (X 109/L)47.59±1.3989.41±1.7262.32 + 1.42*Total Leukocyte count (X 109/L)6.84 + 0.3011.08 + 0.317.45 + 0.65*Red blood cells(X 1012/L)6.30 + 0.383.5 + 0.385.10 + 0.03*Hematocrit (L/L)0.43 + 0.170.26. + 0.200.37 + 0.08*Hemoglobin (g/dl)13.62 + 0.696.63 + 0.9611.80 + 2.96*Platelets (X 109/L)554.80 + 92.23389.50 + 146.10425.10 + 60.8**Significance at p&lt;0.05
Citation Format: Olufemi E. Akanni, Ayodeji Faremi, Aminat O. Agboola, Adekemi R. Akanni, Oluseyi E. Bamisaye. African polyherbal formulation alleviates benzene-induced leukemia in Wistar rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 132. doi:10.1158/1538-7445.AM2017-132
Abstract 1321: Transcriptome-wide association study of prostate cancer risk
Authors: Chen Maxine , Gusev Alexander ,   The PRACTICAL Consortium, Loda Massimo , Mucci Lorelei A. , Stampfer Meir J. , Kraft Peter , Penney Kathryn L. 
Published: July 2017

Abstract
Though more than 150 single nucleotide polymorphisms (SNPs) associated with prostate cancer have been identified through GWAS, we still do not understand the functional consequences of common genetic variation in this disease. Genetic variants may influence complex diseases like prostate cancer through gene expression. However, very large studies evaluating gene expression in prostate cancer are currently infeasible due to the limited availability of prostate cancer tissue and expense of collecting expression data. Alternative approaches have been developed to identify expression-trait associations in study populations without directly measured expression data. One such approach (Gusev et al. Nat Genet. 2016) uses a set of reference individuals with both gene expression and SNP data to develop genetic prediction models of gene expression values. These models are then used to impute cis genetic components of gene expression for a much a larger set of individuals with only genotype and phenotype information. We used Affymetrix gene expression microarray data from normal prostate and prostate tumor tissue and genotype data from prostate cancer patients in the Health Professionals’ Follow-up Study and the Physicians’ Health Study (N=187) as a reference panel for creating the predicted models of the genetic components of expression. We imputed gene expression values into Oncoarray GWAS summary statistics from the PRACTICAL consortium (N ~ 75,000) to assess the association between predicted expression and prostate cancer risk. We present the results of our transcriptome-wide association study in normal prostate and prostate tumor tissue, identifying genes significantly associated with prostate cancer risk after correcting for multiple testing. These genes may provide insight into how genetic variants influence prostate cancer through their effect on gene expression.
Citation Format: Maxine Chen, Alexander Gusev, The PRACTICAL Consortium, Massimo Loda, Lorelei A. Mucci, Meir J. Stampfer, Peter Kraft, Kathryn L. Penney. Transcriptome-wide association study of prostate cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1321. doi:10.1158/1538-7445.AM2017-1321
Abstract 1328: Mechanism of transcriptional regulation of metabotropic glutamate recepter-5 induced by the CXCR4 signaling pathway
Authors: Kuribayashi Nobuyuki , Uchida Daisuke , Kinouchi Makoto , Izumi Sayaka , Kuribayashi Kyoko , Kawamata Hitoshi 
Published: July 2017

Abstract
We have previously demonstrated that stromal cell-derived factor (SDF)-1/CXCR4 system enhances the metastases of oral cancer cells via induction of mGluR5. In this study, we examined the transcriptional regulation of mGluR5 induced by the SDF-1/CXCR4 system, using oral cancer cells, B88, which express functional CXCR4 and have highly metastatic potentials. mGluR5 was markedly induced both by the exogenous SDF-1 addition and overexpression of SDF-1 in B88 cells. These induction was completely inhibited by a MEK inhibitor, U0126, and partially inhibited by a PI3K inhibitor, wortmannin. Furthermore, these inhibitors significantly inhibited the SDF-1/CXCR4 dependent cell-migration in the presence or absence of mGluR5 agonist, DHPG. Recently, several investigators demonstrated that activation of the ERK1/2 pathway is responsible for the transcription of several cancer-associated microRNAs (miRNAs). Thus, we performed miRNA microarray in SDF-1 stimulated B88 cells. we isolated miR-30 family which has predictive binding sites in 3'-UTR of mGluR5 mRNA in silico analysis. We now analyze the regulation of these miRNA by MEK/ERK1/2 and PI3K/Akt pathway.
Citation Format: Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Sayaka Izumi, Kyoko Kuribayashi, Hitoshi Kawamata. Mechanism of transcriptional regulation of metabotropic glutamate recepter-5 induced by the CXCR4 signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1328. doi:10.1158/1538-7445.AM2017-1328