bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2204: Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations reveals new susceptibility loci
Authors: Wu Chen , Wang Zhaoming , Song Xin , Feng Xiao-Shan , Abnet Christian C. , He Jie , Hu Nan , Zuo Xian-Bo , Tan Wen , Zhang Xue-Jun , Freedman Neal D. , Goldstein Alisa M. , Lin Dongxin , Taylor Philip R. , Wang Li-Dong , Chanock Stephen J. 
Published: May 2015

Abstract
We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% Confidence Interval (CI) = 0.82-0.88; P = 7.72x10-20) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10x10-13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (per-allele OR = 1.33, 95% CI = 1.22-1.46; P = 1.99x10-10). Our joint analysis revealed new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.
Citation Format: Chen Wu, Zhaoming Wang, Xin Song, Xiao-Shan Feng, Christian C. Abnet, Jie He, Nan Hu, Xian-Bo Zuo, Wen Tan, Xue-Jun Zhang, Neal D. Freedman, Alisa M. Goldstein, Dongxin Lin, Philip R. Taylor, Li-Dong Wang, Stephen J. Chanock. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations reveals new susceptibility loci. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2204. doi:10.1158/1538-7445.AM2014-2204
Abstract 2206: Genetic variants in selenoprotein genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population
Authors: Li Sharon , Hyland Paula L. , Freedman Neal D. , Hu Nan , Su Hua , Wang Lemin , Wang Chaoyu , Ding Ti , Wang Yuan , Fan Jin-Hu , Qiao You-Lin , Xiong Xiaoqin , Yu Kai , Goldstein Alisa M. , Dawsey Sanford M. , Taylor Philip R. , Abnet Christian C. , Lin Shih-Wen 
Published: May 2015

Abstract
PURPOSE: Several observational studies and multinutrient interventional trials suggest that selenium compounds have potential chemopreventive effects on esophageal and gastric carcinogenesis, presumably via their influence on selenoproteins. We aimed to investigate associations between genetic variants in selenoprotein genes and risk of esophageal squamous cell carcinoma (ESCC), gastric carcinoma (GC) and GC subsets: cardia (GCA) and non-cardia (GNCA) using data from a genome-wide association study in a Han Chinese population in which ESCC and GC are predominant cancers. METHODS: 1944 ESCC cases, 1758 GC cases (1126 GCA and 632 GNCA) and 2111 controls from the Shanxi Upper GI Cancer Genetics project and the Linxian Nutritional Intervential Trials were genotyped for 243 SNPs in 24 selenoprotein genes. Logistic regression models were applied to evaluate SNP-level associations. Pathway- and gene-level associations were determined using the resampling-based adaptive rank-truncated product approach. RESULTS: Selenoproteins as a whole pathway were not significantly associated with ESCC (p=0.398) or GC (p=0.608), but five significant (p&lt;0.05) gene-level associations were identified, including GPX2 (p=0.008) and GPX5 (p=0.006) with ESCC, DIO2 (p=0.026) with GC, and SEPP1 (p=0.007) and SEPW1 (p=0.004) with GCA. CONCLUSION: Our results show evidence for an association between specific selenoprotein genes and the risk of ESCC and GC, warranting further studies to validate these associations and investigate underlying mechanisms.
Citation Format: Sharon Li, Paula L. Hyland, Neal D. Freedman, Nan Hu, Hua Su, Lemin Wang, Chaoyu Wang, Ti Ding, Yuan Wang, Jin-Hu Fan, You-Lin Qiao, Xiaoqin Xiong, Kai Yu, Alisa M. Goldstein, Sanford M. Dawsey, Philip R. Taylor, Christian C. Abnet, Shih-Wen Lin. Genetic variants in selenoprotein genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2206. doi:10.1158/1538-7445.AM2014-2206
Abstract 2207: An analysis of circulating sex steroid hormones in relation to Barrett's esophagus
Authors: Cook Michael B. , Wood Shannon , Cash Brooks D. , Young Patrick , Acosta Ruben D. , Falk Roni T. , Pfeiffer Ruth , Hu Nan , Giffen Carol , Turcotte Veronique , Caron Patrick , Guillemette Chantal , Dawsey Sanford M. , Abnet Christian C. , Hyland Paula L. , Taylor Philip R. 
Published: May 2015

Abstract
Introduction: Barrett's esophagus (BE) is the precursor lesion of esophageal adenocarcinoma (EA). The male-to-female incidence rate ratio of BE is ∼2 while EA is ∼6 for reasons that remain unknown. We assessed whether sex steroid hormones were associated with BE in a male population. Methods: The Barrett's Esophagus Early Detection Case Control Study (BEEDS) was based at the National Naval Medical Center (NMMC). We quantitated 13 sex steroid hormones, using mass spectrometry, and sex hormone binding globulin (SHBG), using ELISA, in 173 male BE patients and 213 endoscopy-negative controls. We also calculated free estradiol and free testosterone using formulas known to accurately estimate such. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for smoking status, alcohol consumption, body mass index (BMI; kg/m2), heartburn, regurgitation, and gastroesophageal symptom score (excluding heartburn and regurgitation). Results: Free testosterone was positively associated with BE risk, peaking in the highest quartile with an OR of 4.42 (95%CI: 1.91, 10.24, p=0.0005). Estrone-sulphate was inversely associated with BE risk (OR 4th quartile=0.23, 95%CI:0.10, 0.53, p=0.0006). No other hormone was associated with BE risk. Relationships were not modified by age or BMI. Conclusion: High testosterone may delay re-epithelization of esophageal lesions leading to increased risk of metaplastic growth.
Citation Format: Michael B. Cook, Shannon Wood, Brooks D. Cash, Patrick Young, Ruben D. Acosta, Roni T. Falk, Ruth Pfeiffer, Nan Hu, Carol Giffen, Veronique Turcotte, Patrick Caron, Chantal Guillemette, Sanford M. Dawsey, Christian C. Abnet, Paula L. Hyland, Philip R. Taylor. An analysis of circulating sex steroid hormones in relation to Barrett's esophagus. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2207. doi:10.1158/1538-7445.AM2014-2207
Abstract 2212: Urinary biomarkers of catechins in relation to risk of hepatocellular carcinoma in the Shanghai Cohort Study
Authors: Huang Joyce Y. , Butler Lesley M. , Wang Renwei , Yang Chung S. , Yuan Jian-Min , Gao Yu-Tang 
Published: May 2015

Abstract
Background: Catechins from tea and non-tea sources are potential anti-carcinogenic compounds with potent antioxidant properties. Data supporting an effect of specific catechins on the risk of hepatocellular carcinoma (HCC) in humans are sparse. We examined the association between urinary biomarkers of catechins and their metabolites and risk of HCC. Methods: A nested case-control study of HCC (221 cases and 1072 matched controls) was conducted within the Shanghai Cohort Study, a cohort of 18,244 men who were enrolled in 1986-1989. Specific catechins and their metabolites including epicatechin (EC), epigallocatechin (EGC), 4′-O-methyl-epigallocatechin (4′-MeEGC), (-)-5-(3′, 4′, 5′-trihydroxyphenyl)-gamma-valerolactone (M4), and (-)-5-(3′, 4′-dihydroxyphenyl)-gamma-valerolactone (M6) were quantified in urine samples collected from study subjects at enrollment. Logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) with adjustment for established risk factors for HCC, including hepatitis B surface antigen (HBsAg) serology status, self-reported physician-diagnosed cirrhosis, cigarette smoking, and alcohol drinking. Results: Compared with men who had no detectable EC, men with detectable levels of urinary EC had a statistically significant lower risk of HCC (OR=0.64; 95% CI: 0.45, 0.92). The inverse association between EC and HCC risk was not modified by smoking, alcohol intake or HBsAg/cirrhosis status. This inverse EC-HCC association strengthened in analyses restricted to cases that were diagnosed 10 or more years after specimen collection (OR=0.40; 95% CI: 0.22, 0.71). There was no association between urinary levels of EGC or other catechin metabolites and HCC risk. Conclusion: In our study population green tea is the sole source of dietary EGC while the major sources of EC include green tea, as well as apples, black grapes, soybeans, and broad beans. Thus, the findings of the present study support the notion that consumption of fruits and legumes may have a beneficial effect on HCC risk. Experimental studies are warranted to elucidate the biologic mechanisms of EC in hepatocarcinogenesis.
Citation Format: Joyce Y. Huang, Lesley M. Butler, Renwei Wang, Chung S. Yang, Jian-Min Yuan, Yu-Tang Gao. Urinary biomarkers of catechins in relation to risk of hepatocellular carcinoma in the Shanghai Cohort Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2212. doi:10.1158/1538-7445.AM2014-2212
Abstract 2216: 6q15 deletion impede development of ERG fusion in prostate cancer
Authors: Kluth Martina , Tsourlakis Maria Christina , Meyer David , Krohn Antje , Freudenthaler Fabian , Bauer Melanie , Salomon Georg , Heinzer Hans , Michl Uwe , Steurer Stefan , Simon Ronald , Sauter Guido , Schlomm Thorsten , Minner Sarah Jane Pauline 
Published: May 2015

Abstract
Deletions at chromosome 6q15 belong one to the most frequent alterations in pros-tate cancer, and are linked to poor prognosis. Furthermore, there is a marked inverse relationship between 6q15 deletions and TMPRSS2:ERG fusions in prostate cancer. While heterogeneity may limit the applicability of diagnostic molecular markers, it is important to estimate in vivo heterogeneity and the sequel of appearance of potential prognostic markers. In case of one alteration developing after the other, we would expect a small area of cancer having both alterations within a larger area having only one (the first appearing) of these changes.
In this study, we used our heterogeneity tissue microarray approach as a surrogate method to determine in vivo heterogeneity of 6q15 deletions and TMPRSS2:ERG fusions. We constructed a heterogeneity TMA containing samples taken from 10 dif-ferent tumor containing tissue blocks of 189 prostate cancers. Each prostate con-tained 1 to 6 individual cancer foci allowing the molecular analysis of more than 350 tumor foci. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG expression by immunohistochemistry.
Only 6.6% of 334 ERG positive but 28.4% of 440 ERG negative TMA spots showed 6q15 deletions (p&lt;0.0001). A breakdown of these data to the level of tumor foci re-vealed 6q deletions in 34 tumor foci that were large enough to have at least 3 ana-lyzable TMA spots. The cohort included 42 tumor foci with a homogeneous ERG pos-itivity and 15 with a homogeneous 6q deletion. Remarkably, six of 42 homogeneously ERG positive tumor foci (14.3%) were focal 6q15-deleted, but none of 16 homogene-ous 6q15-deleted foci showed focal ERG positivity in the same tumor area (p=0.022).
In conclusion of our study, the complete absence of ERG positive tumor foci in 6q15-deleted cancers suggests that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions. However, the development of 6q15 deletions is independent of the ERG status.
Citation Format: Martina Kluth, Maria Christina Tsourlakis, David Meyer, Antje Krohn, Fabian Freudenthaler, Melanie Bauer, Georg Salomon, Hans Heinzer, Uwe Michl, Stefan Steurer, Ronald Simon, Guido Sauter, Thorsten Schlomm, Sarah Jane Pauline Minner. 6q15 deletion impede development of ERG fusion in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2014-2216
Abstract 2218: Genomic characterisation of 1015 cancer cell-lines
Authors: Bignell Graham R. , Iorio Francesco , Futreal Andrew , Stratton Michael R. , Campbell Peter , McDermott Ultan 
Published: May 2015

Abstract
Over the last twenty years there has been a paradigm shift in cancer treatment, moving away from the cytotoxic effects of chemicals targeting all cells going through cell division to a more targeted approach aimed at inactivating specific cellular components upon which the cancers rely to drive cell growth, a process termed oncogene addiction. The ‘poster child’ for such therapies is ‘imatinib' a small molecule inhibitor of ABL kinase activity targeting the BCR-ABL fusion protein in CML.
We present the genomic characterisation of 1015 cancer cell lines currently being used as reagents in a high-throughput screen of anti-cancer agents. Future analysis combining these genomic and drug resistance data will aid in identifying the underlying genetics of drug sensitivity and allow for identification of biomarkers with which to stratify patients, identifying those most likely to respond to specific cancer therapies. To characterise the cell lines we performed exome sequencing and copy number analysis. Since most cell lines are unmatched we screened out germline variants by comparison to ∼8000 normal exomes, giving a set of ∼500,000 putative somatic non-synonymous variants. To reduce the ‘genetic space’ for the subsequent downstream correlation to drug response data we further filtered the variants to identify those most likely to have a functional effect or contribute to carcinogenesis. Two such filters were applied, the ‘Functional Analysis through Hidden Markov Models’ (FATHMM) algorithm and a series of checks identifying recurrence of variants in the ‘systematic screening data' held in the COSMIC database. Application of these filters reduced the number of variants to be taken forward to ∼115,000 and 30,000 respectively. The variant data for the cancer cell lines is available via the COSMIC web portal.
Citation Format: Graham R. Bignell, Francesco Iorio, Andrew Futreal, Michael R. Stratton, Peter Campbell, Ultan McDermott. Genomic characterisation of 1015 cancer cell-lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2218. doi:10.1158/1538-7445.AM2014-2218
Abstract 2222: Synergistic effects of NAT2 and GSTT1 null polymorphism in lung cancer: a study from North India
Authors: Shukla Rajni Kant , Kant Surya , Bhattacharya Sandeep , Mittal Balraj K. 
Published: May 2015

Abstract
Purpose: Polymorphism in carcinogen detoxification enzymes, NAT2 and GSTT1, has been suggested as susceptibility factor for DNA damage and lung cancer. However, little information is available on DNA adduct burden in lung tissue and polymorphisms in NAT2 and GSTs gene. We investigated the independent and combined effect of metabolic gene polymorphisms NAT2 and GSTs in lung cancer north India patients.
Aim: Present study was conducted to examine: 1) whether GSTT1 Null and NAT2 genotypes have combined risk factors for Lung cancer, 2) To study possible association of tobacco smoking with NAT2 and GSTT1 null genotype of these patients.
Materials and Methods: This case control study was undertaken over a period of 19 months and included 100 Lung cancer patients and 145 controls. The GSTT1 Null and NAT2 genotypes were identified by PCR-RFLP method in peripheral blood DNA samples. Genotypes frequencies and the association of the genotypes among patients and controls group were assessed by X2 test and Binary Logistic regression.
Results: The NAT2 slow acetylator genotype frequency of slow or fast acetylator genotypes was not significant in lung cancer patients alone (OR = 1.18, 95% CI: 0.69 - 2.03, p value = 0.583).when we combined GSTT1Null/NAT2 slow, then we found no significant association (OR = 0.85, 95% CI: 0.47 - 1.54, p value = 0.610) between case and controls. While on comparing data with smoker as well non-smoker NAT2 polymorphism have no association but GSTT1 null have significant association (P=0.004) in smoker patients.
Conclusion: These data demonstrate that there have no combined affect GSTT1 Null NAT2 slow acetylator genotype did not associated with the risk of developing lung cancer in North Indian population when compared with controls.
Note: This abstract was not presented at the meeting.
Citation Format: Rajni Kant Shukla, Surya Kant, Sandeep Bhattacharya, Balraj K. Mittal. Synergistic effects of NAT2 and GSTT1 null polymorphism in lung cancer: a study from North India. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2222. doi:10.1158/1538-7445.AM2014-2222
Abstract 2223: Genome-wide analysis of copy number alterations and gene mutations in testicular germ cell cancer
Authors: Sato Yusuke , Sato-Otsubo Aiko , Nagata Yasunobu , Yoshida Kenichi , Shiraishi Yuichi , Suzuki Hiromichi , Sanada Masashi , Kume Haruki , Miyano Satoru , Homma Yukio , Ogawa Seishi 
Published: May 2015

Abstract
Introduction and Objective
Testicular germ cell cancer (TGCC) is the most common solid malignancy among young adult males. Cure could be obtained by intensive chemotherapy combined with retroperitoneal lymph node dissection, but often with substantially compromised quality of life. As for the common genetic lesions, somatic mutations and amplifications of KIT are found in about 20%-30% of cases with TGCCs. However, the molecular pathogenesis of TGCC is still poorly understood. In this study, to obtain a better understanding of the genetic basis of TGCC and to identify druggable molecular targets, we performed whole exome sequencing as well as SNP array-based copy number analysis in TGCC.
Methods
All cases underwent high orchiectomy and were histologically diagnosed as TGCC. Genomic DNA was extracted from fresh frozen specimens of TGCC. Whole exome sequencing was performed for paired tumor/normal DNA from 10 TGCC patients, in which target exomes were captured using SureSelect Human All Exon V5 (Agilent Technologies) and subjected to massively parallel sequencing on the Illumina platform (HiSeq2000). Copy number variants were also interrogated in 40 TGCCs (25 seminomas and 15 non-seminomas) using Affymetrix 250K NspI array.
Results
TGCC genome was triploid in most cases with high level amplification in12p. Loss of heterozygosity (LOH) of chromosome 4 was frequently observed in both seminoma and non-seminoma, whereas 11q deletion was found predominantly in cases with seminoma. In addition, we identified recurrent focal amplifications involving 4q12 and 22q11, from which KIT and MAPK1 were identified, respectively. In whole exome sequencing, 15 somatic mutations were detected per sample on average, which was relatively lower than other solid malignancies. When combined the results of copy number analysis with those of whole-exome sequencing, genes involved in RAS signaling pathway and chromatin modification were frequently altered in TGCC.
Conclusions
Our comprehensive analyses revealed genomic aberrations of TGCC in terms of copy number alterations and gene mutations. Mutated/amplified KIT and MAPK1 and other RAS pathway gene could be potential targets of small molecule inhibitors for therapeutics.
Citation Format: Yusuke Sato, Aiko Sato-Otsubo, Yasunobu Nagata, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Masashi Sanada, Haruki Kume, Satoru Miyano, Yukio Homma, Seishi Ogawa. Genome-wide analysis of copy number alterations and gene mutations in testicular germ cell cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2223. doi:10.1158/1538-7445.AM2014-2223
Abstract 2225: Comprehensive molecular characterization of esophageal squamous cell carcinoma
Authors: Lin Dechen , Meng Xuan , Xu Liang , Ding Lingwen , Garg Manoj , Yang Henry , Liu Lizhen , Hao Jiajie , Wang Mingrong , Nagata Yasunobu , Sato Yusuke , Okuno Yusuke , Ogawa Seishi , Koeffler Phillip 
Published: May 2015

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is a world-wide prevalent cancer, which is particularly common in certain regions of Asia. However, the genetic alterations of this disease have not been fully described.
Methods
We determined the mutational landscape of ESCC through whole-exome or targeted deep sequencing of 139 tumor/germline pairs. The somatic copy number variations (SCNV) of over 180 ESCC tumors were analyzed by SNP-array or array-CGH. Candidate driver mutations were mathematically calculated by the most updated algorithm MutSigCV, and the protein expression of which were thoroughly evaluated by immunohistochemistry. Finally, biological effects of candidate drivers were examined through functional studies in vitro and in vivo.
Results
Deep sequencing and computational analysis identified frequent and novel driver mutations affecting genes such as FAT1 (11.5%), ZNF750 (7.2%), EP300 (7.9%) and MLL2 (18.0%). FAT1 and ZNF750 genes were homozygouly deleted in 3.5% and 3.4% ESCCs, respectively, and their RNA transcripts and proteins were expressed at much lower levels in primary tumors compared to adjacent normal esophageal epithelial. Importantly, silencing of wild-type FAT1 or ZNF750 expression with siRNA/shRNAs significantly promoted cell proliferation and decreased cell differentiation, whereas ectopic expression of these genes resulted in opposite biological consequences. These genetic alterations and biological evidence strongly suggest that FAT1 and ZNF750 likely encode tumor suppressors which are frequently disrupted in ESCC. Furthermore, by integrating the landscape of somatic mutation, SCNV and protein dysregulation, we proposed that RTK-PI3K-MAPK pathways, cell cycle and epigenetic regulation are frequently altered by multiple molecular mechanisms in esophageal tumors. Finally, our systematic approaches uncovered many novel druggable candidates in this disease, such as FGFR1, ALK and XPO1.
Conclusions
By demonstrating the genomic landscape of over 180 ESCC cases, our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
Citation Format: Dechen Lin, Xuan Meng, Liang Xu, Lingwen Ding, Manoj Garg, Henry Yang, Lizhen Liu, Jiajie Hao, Mingrong Wang, Yasunobu Nagata, Yusuke Sato, Yusuke Okuno, Seishi Ogawa, Phillip Koeffler. Comprehensive molecular characterization of esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2225. doi:10.1158/1538-7445.AM2014-2225