bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1634: Metabolomic profiling for early detection of colorectal neoplasia
Authors: Montrose David C. , Kopelovich Levy , Zhou Xi Kathy , Yantiss Rhonda , Subbaramaiah Kotha , Dannenberg Andrew 
Published: August 2012

Abstract
Introduction: Colorectal cancer (CRC) is the 3rd leading cause of cancer-related deaths in the world. Colonoscopy is widely used for early detection and removal of colorectal neoplasia to prevent CRC. However, it is both invasive and costly underscoring the need for new strategies to identify subjects for whom colonoscopy is most appropriate. Metabolomics is a high throughput method of detecting small molecules which provides a platform for identifying novel biomarkers of colorectal neoplasia. In this study, we investigated whether metabolic changes could be identified in the feces and plasma in a model of experimental CRC. Methods: Five week old male A/J mice were administered six weekly intraperitoneal injections of either azoxymethane (AOM) (10mg/kg) (n=40) or 0.9% saline (n=35). Following injections, feces, plasma and tumor tissue or normal colonic mucosa were collected and stored at −80oC for metabolomic analysis. Five mice from the AOM injected group were sacrificed at each of three time points (three, five and seven weeks after the last injection) to assess tumor burden. UPLC/MS/MS and GC/MS were used to quantify metabolite levels in feces, plasma and tissue. Results: Histological analysis of tumor burden in the colon showed a progressive increase as a function of time after AOM administration. Metabolomic analysis revealed a large number of significantly changed metabolite levels in both the feces and plasma during colon carcinogenesis. These included amino acids and peptides in feces as well as bile acids in the plasma. A select number of these metabolites were found to progressively change as a function of time in both feces and plasma in relation to increased tumor burden. Significantly, certain metabolites changed in the same direction in feces and tumor tissue, plasma and tumor tissue as well as across all three matrices, suggesting that these may be tumor-derived. For example, samples from AOM injected mice showed increased levels of sarcosine and 2-hydroxyglutarate, metabolites previously implicated in prostate cancer and gliomas/AML, respectively. Conclusions: This study demonstrates the potential utility of metabolomic analyses for the early detection of colorectal neoplasia. Additionally, the finding of increased levels of two onco-metabolites (sarcosine, 2-hydroxyglutarate) in colorectal neoplasia suggests their potential involvement in colon carcinogenesis. Future studies in humans will be required to determine the significance of these findings.
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 1634. doi:1538-7445.AM2012-1634
Abstract 1635: Effect of dietary fish oil on rat colonic prostaglandin (PG) E2 metabolism
Authors: Jiang Yan , Ren Jianwei , Waters Ian , Smith William L. , Brenner Dean E. 
Published: August 2012

Abstract
PGE2, an eicosanoid generated from arachidonic acid (AA) by the cyclooxygenase function of prostaglandin H synthases (PGHS)-1 and 2, has been linked to the risk of many cancers including colorectal carcinogenesis. Targeting colonic PGE2 homeostasis by utilizing nutritional products such as fish oil may reduce endogenous PGE2 that, in turn, may decrease subsequent inflammatory events that lead to carcinogenesis. Rats were fed high fat fish oil diets contained different ratios of eicosapentaenoic acid (EPA) and n-6 fatty acid. The colon was horizontally divided into three equal length transections, first (proximal end), second (transverse) and third (distal end). Enzymes involved in PGE2 metabolism (15-hydroxyprostaglandin dehydrogenase (15-PGDH) and PGE synthase (mPGES)) were measured using quantitative PCR and semi-quantitative Western Blotting. GC-MS analysis was performed to detect fatty acid levels in serum and colon. LC-MS/MS analysis was used to examine eicosanoid levels. Our results showed that the colonic epithelial mucosa contained less PGE2 per mg of protein than did the whole colon. Colonic PGE2 and several eicosanoids including 13-Hydroxyoctadecadienoic acid(13HODE), 5-Hydroxyeico-satetraenoic acid (5 HETE), 15-Hydroxyeicosatetraenoic acid (15 HETE) and 12-Hydroxyeicosatetraenoic acid (12 HETE) were distributed differentially in different part of the colon. Dietary fish oil intake increased tissue levels of EPA in the colon. PGHS-2 gene was affected the most by dietary fish oil among all the genes tested in normal colon. Fish oil dose-dependently decreased PGHS-2 mRNA expression in all three colon sections. mRNA expression of 15-PGDH was higher in the third colonic section than the first two sections; however it was not altered by dietary fish oil. In conclusion, different parts of the colon have different eicosanoid profiles. The decreases in PGE2 in normal colon observed with fish oil feeding do not appear to be related to expression of PGHS-1, mPGES and 15-PGDH but are most closely correlated with PGHS-2 despite that PGHS-2 levels are already low in the normal colon. These data support the concept of anatomic variability in colonic carcinogenesis.
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 1635. doi:1538-7445.AM2012-1635
Abstract 164: High throughput homogenous bioluminescent assays for monitoring the concentrations of AMP, ADP and ATP
Authors: Goueli Said A. , Hsiao Kevin , Zegzouti Hicham 
Published: August 2012

Abstract
Adenine nucleotides are major determinants of the energy status of the cell and thus any modulation of their cellular concentration has significant consequences to cellular metabolism, cellular growth and cell death. ATP generating enzymes are usually involved in anabolic processes while ATP consuming enzymes are involved in catabolite processes. We have developed biochemical assays that monitor the concentrations of ATP, ADP and AMP in a biochemical reaction. For instance ATP depletion dependent assays and ADP generating assays monitor the activity of kinases and ATPases. These universal assays can measure the activity of various enzymes with no modification of the native substrate and the ability to use diverse substrates such as proteins, peptides, lipids, sugars, etc. The AMP generating reactions such as ubiquitin ligases, aa aminoacyl t-RNA synthetases, DNA ligases, cAMP-dependent phosphodiesterases, etc. can be also monitored with high sensitivity and reproducibility. We will show data using these various technologies in monitoring the various adenine nucleotide concentrations in biochemical reactions.
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 164. doi:1538-7445.AM2012-164
Abstract 1642: Rare missense variants in MAP3K14 and ARHGAP27 in men with hereditary prostate cancer
Authors: Ishak Miriam B. , Ray Anna M. , Robbins Christiane M. , Tembe Waibhav D. , Carpten John D. , Lange Ethan M. , Isaacs William B. , Cooney Kathleen A. 
Published: August 2012

Abstract
Background: Linkage studies have consistently identified the 17q21-22 chromosomal region to be important in hereditary prostate cancer, although no known causal variant has yet been identified. Three genes in this region are potential candidates based on known function as well as location in our region of interest. Mitogen-activated protein kinase kinase kinase 14 (MAP3k14) encodes a serine-threonine protein kinase that stimulates NF-κβ activity. The ARHGAP27 gene codes for a Rho-like small GTPase-activating protein and RND2 is part of the Rho GTPase family implicated in endosomal trafficking. Methods: All exons within the 17q21-22 chromosomal region were interrogated in 94 probands from hereditary prostate cancer families and linkage to the 17q21-22 region. Participants were from the University of Michigan Prostate Cancer Genetics Project and Johns Hopkins University. Enrichment was performed using the RainDance Technology following an emulsion PCR protocol. Sequencing was performed on the ABI SOLiD platform. Confirmation of mutation status among family members (both affected and unaffected) was performed using Sanger sequencing. Results: No deleterious truncating mutations were detected in the three candidate genes. Although missense variants were not observed in RND2, five missense variants were identified in the MAP3k14 and ARHGAP27 genes. Four of the five variants are novel (not described in dbSNP) and four out of the five variants are predicted to be damaging on protein function by SIFT and/or PolyPhen. Several of these variants demonstrated evidence of cosegregation within families based on sequencing of family members. Conclusions: We have identified five missense variants in MAP3k14 and ARHGAP27 in men with hereditary prostate cancer. Further research is ongoing in the laboratory to determine the frequency of these variants in a large prostate cancer case-control study.
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 1642. doi:1538-7445.AM2012-1642
Abstract 1645: Genome-wide association studies identify several new loci for human pigmentation traits
Authors: Zhang Mingfeng , Queshi Abrar , Zhang Jiangwen , Liang Liming , Han Jiali 
Published: August 2012

Abstract
Genome-wide association studies (GWASs) have been widely conducted and numerous new loci have been associated with various outcomes. Multiple GWASs have been completed in the Nurses’ Health Study and the Health Professionals Follow-up Study, and we have accrued more than 15,000 individuals with genome-wide genotype data. More recently, with the data released from the 1000 Genomes Project, we have imputed about 10 million SNPs based on the genotyped SNPs and haplotypes from the 1000 Genomes Project. Based on the knowledge that light human pigmentation is a host risk factor for skin cancer development, we conducted the GWASs on pigmentary traits in multiple GWAS datasets in the two cohorts using the newly imputed data. We systematically evaluated the traits of natural hair color (ordinal coding from blonde, light brown, dark brown to black, excluding red hair color), eye colors (blue, green and brown eye colors as co-dominant outcomes), tanning ability (ordinal coding from practically no tan, moderate tan to deep tan) and the number of sunburns (continuous variable). We adjusted for the four largest principal components of genetic variation in the regression model for each component dataset, and performed a meta-analysis to combine the results of all these datasets. No systematic deviation from the expected distribution was detected for any of these pigmentation GWASs. Using a multistage study design, we identified a new region on chromosome 13q22 associated with natural hair color that reached the GWAS significance level. The most significant SNP in this region reached a p-value of 2.4 ×10−14 (p = 5.4×10−9 in the discovery stage and p = 1.2×10−6 in the replication stage). We also newly identified and replicated the association of a SNP on 1q32.3 with brown eye color (p = 7.0×10−8 in the combined set), a SNP on 5p15 with green eye color (p = 9.1×10−7 in the combined set), and a SNP on 11q25 with the number of sunburns (p = 5.6×10−6 in the combined set). Of note, the SNP associated with the number of sunburns was also associated with the expression of a local gene based on the transcript expression profiling data of 87 HapMap CEU cell lines (NCBI GEO database, accession GSE7792). These novel pigmentation SNPs identified by our GWASs are strong candidates to evaluate skin cancer risk.
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 1645. doi:1538-7445.AM2012-1645
Abstract 1647: Evaluation of breast cancer susceptibility loci in Chinese women from Singapore
Authors: Chan Maurice , Ji Shen Mo , Liaw Chiew Suan , Yap Yoon Sim , Law Hai Yang , Yoon Chui Sheun , Wong Chow Yin , Ong Kong Wee , Madhukumar Preetha , Wong Nan Soon , Ng Raymond , Yong Wei Sean , Li Hui Hua , Tan Puay Hoon , Ho Gay Hui , Ang Peter , Lee Ann SG 
Published: August 2012

Abstract
Genome-wide association studies (GWAS) have identified several breast cancer susceptibility loci associated with European populations, some of which were also found to be associated with breast cancer among women in China. Women in Singapore are predominantly of Chinese ancestry with an urbanized lifestyle, with breast cancer rates approaching those of the West. To explore the role of these breast cancer susceptibility variants, a Taqman-based microfluidics strategy was established to carry out fast track replication of 22 SNPs for 1,146 cases and 1,534 controls to identify significant risk variants for breast cancer. Interestingly, the most significant SNP [rs2046210; odds ratio (OR), 1.4; 95% confidence interval, 1.2-1.6; P=7x10−6], residing in 6q25.1, had been initially identified in a Chinese population, suggesting a strong and consistent association of this SNP with Chinese ancestry. SNPs in FGFR2 (rs2981579, rs1219648, rs2981582, rs112000014), 8q24 (rs13281615), and MAP3K1 (rs16886165) showed significant associations similar to those observed in women of European ancestry, with ORs ranging from 1.1 to 1.7 (P=5x10−5 to 0.04). Ranking of the SNPs in terms of their ORs for Singaporean Chinese women was compared to that from Western and Chinese studies. The ranking for Singaporean Chinese women resembled, but was not identical to, that of women in China, reflecting the effect of ethnicity. Comprehensive annotation of the genotyping data with associated clinicopathological features enabled the identification of significant SNPs associated with tumour size, lymph node metastasis, and estrogen/progesterone receptor status. Findings from this study implicate 6q25.1 and FGFR2 as the most important susceptibility loci for Asian women of Chinese ancestry and may guide future fine-mapping studies to identify causal variants.
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 1647. doi:1538-7445.AM2012-1647
Abstract 1648: MICA variation and soluble MICA are possible prognostic biomarkers for HBV-induced hepatocellular carcinoma
Authors: Matsuda Koichi , Kumar Vinod , Nakamura Yusuke 
Published: August 2012

Abstract
Hepatitis B virus (HBV) infection still remains to be one of the dominant risk factor for hepatocellular carcinoma (HCC). Both genetic as well as environmental factors influence the progression of chronic hepatitis B (CHB) to HCC. MHC class I polypeptide-related chain A and B (MICA and MICB) molecules are induced in response to viral infection as well as various stresses. We have recently revealed that SNP in MICA promoter was significantly associated with HCV-induced HCC risk as well as lower sMICA level in serum. To investigate the possible involvement of MICA in hepatocellular carcinogenesis caused by HBV-infection, we analyzed MICA gene polymorphisms and the levels of soluble MICA (sMICA) in HBV-induced HCC patients. The genetic association analysis revealed a nominal association at rs2596542 in which G allele was associated with susceptibility to HBV-induced HCC (P=0.029 with odds ratio of 1.19). We also found a significant elevation of sMICA in HBV-induced HCC cases. Moreover, genotypes at SNP rs2596542 located in the upstream of MICA promoter, was significantly associated with sMICA levels (P = 0.009). Interestingly. HCC patients with high sMICA (&gt; 5 pg/ml) exhibited poor prognosis compared with patients with low sMICA (P = 0.008). Thus, our results highlight the importance of MICA genetic variations and sMICA as predictive biomarkers for HBV-induced HCC.
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 1648. doi:1538-7445.AM2012-1648
Abstract 1657: Genome-wide association study of lung cancer: Variation in TP63 gene confers the risk of lung adenocarcinoma
Authors: Daigo Yataro , Nakamura Yusuke 
Published: August 2012

Abstract
Lung cancer is the most common cause of death from cancer worldwide, and its incidence is increasing in East Asian and Western countries. Lung cancer comprises various types of histology that are often divided into two main types, non-small cell lung cancer and small cell lung cancer. Each type has different pathophysiological and clinical features, suggesting that their mechanisms of carcinogenesis differ. Adencarcinoma accounts for about 50% of all histological types of lung cancer, and its incidence is increasing in East Asian and Western countries. Because most of the current genome-wide association studies (GWAS) on lung cancer have been conducted in European populations with a full range of different histological types of lung cancer, GWAS that focus on individual histological groups with archived clinicopathological features are required. To identify genetic factors that modify the risk of lung adenocarcinoma, we conducted a genome-wide association study in a Japanese cohort, with replication in two independent studies in Japanese and Korean individuals, in a total of 2,098 lung adenocarcinoma cases and 11,048 controls. The combined analyses identified two susceptibility loci for lung adenocarcinoma: TERT (rs2736100, combined P = 2.91 × 10(-11), odds ratio (OR) = 1.27) and TP63 (rs10937405, combined P = 7.26 × 10(-12), OR = 1.31). When we analyzed the combinational combined effect of TP63 and TERT, we found that these two susceptibility genes showed a synergistic effect on the risk of lung adenocarcinoma (OR = 4.26). Fine mapping and re-sequencing of the region containing TP63 showed that a SNP (rs4488809) in intron 1 of TP63 showed the most significant association. Our results suggest that genetic variation in TP63 may influence susceptibility to lung adenocarcinoma in East Asian populations. Further functional studies are necessary to clarify the mechanisms by which TP63 influences susceptibility to lung adenocarcinoma. We will also report additional studies of TP63 on other ethnic populations as well as other histological types of lung cancer that will provide detailed information on the genetic etiology and heterogeneity of lung 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 1657. doi:1538-7445.AM2012-1657
Abstract 1658: Post-GWAS genetic and functional studies for bladder cancer: An uncommon protective synonymous coding variant within the UGT1A6 gene explains the GWAS signal and affects cellular detoxification
Authors: Tang Wei , Fu Yi-Ping , Figueroa Jonine D. , Malats Nuria , Garcia-Closas Montserrat , Chatterjee Nilanjan , Kogevinas Manolis , Chanock Stephen J. , Silverman Debra T. , Rothman Nathaniel , Prokunina-Olsson Ludmila 
Published: August 2012

Abstract
Background: A recent genome-wide association study (GWAS) of bladder cancer identified a single nucleotide polymorphism (SNP), rs11892031, within the UGT1A gene cluster on chromosome 2q37.1, as a novel risk factor. UGT1A locus encodes nine UGT proteins that belong to phase II cellular detoxification system. UGTs are functionally important for detoxification of aromatic amines, which are known risk factors for bladder cancer found in industrial chemicals and tobacco smoke. UGTs are composed of shared exons 2-5 and individual alternative first exons that define enzymatic activity and substrate specificity. Materials and results: We sequenced all nine highly similar alternative first exons of UGT genes in more than 2,000 individuals and identified 27 non-synonymous and 19 synonymous known coding variants, but no novel variants. Imputation based on the GWAS dataset, a combined reference panel of HapMap 3 and 1000 Genomes Projects, and a subset of GWAS samples genotyped for all the identified coding variants, generated data for 1,170 SNPs within the whole UGT region. Of these markers, the strongest association was detected for an uncommon (MAF&lt;0.03) protective genetic variant rs17863783 (OR=0.55, 95%CI=0.44-0.69, p=3.3x10-7 in 4,035 cases and 5, 284 controls; D’=0.96, r2=0.23 with rs11892031). No residual association in this region was detected after adjustment for rs17863783. Rs17863783 is a synonymous coding variant Val209Val within the functional UGT1A6.1 splicing form, strongly expressed in the liver, kidney and bladder. We found the protective T allele of rs17863783 to be associated with increased mRNA expression of UGT1A6.1 in in-vitro exontrap assays and in human liver tissue samples. We suggest rs17863783 may protect from bladder cancer by increasing the removal of carcinogens from bladder epithelium by the UGT1A6.1 protein. Conclusions: Our study shows an example of genetic and functional role of an uncommon protective genetic variant in a complex human disease such as bladder 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 1658. doi:1538-7445.AM2012-1658