bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4146: Polymorphisms of GSTT1, APE1 and MUTYh gene and the risk of oral squamous cell carcinoma
Authors: Lai Chih-Hsiung , Chiu Li-Ling , Chien Huei-Tzu , Liou Saou-Hsing , Huang Shiang-Fu , Chen I-How , Liao Chun-Ta , Hsieh Ling-Ling 
Published: May 2015

Abstract
In Taiwan, oral cancer (including sub-sites in the oral cavity, oropharynx and hypopharynx) is the fourth most common cancer in men. According to the cancer registry report from the Ministry of Health and Welfare of the Executive Yuan, the annual age-adjusted incidence for oral cancer in males has shown a 1.55-fold increase in the past decade. Cigarette smoking, areca quid (AQ) chewing and alcohol drinking have been unveiled as the major risk factors. Previous studies have implicated that oxidative stress generated from cigarette smoking, AQ chewing and alcohol drinking contributed to oral cancer development. It is well known that GSTM1 and GSTT1 are involved in the detoxification of oxidative free radicals and nearly all oxidative DNA lesions are repaired via the DNA base excision repair (BER) pathway. To investigate the role of GSTM1, GSTT1 and BER genes (including OGG1, APE1, MUTYh, WRN and XRCC1) involved in OSCC risk in Taiwan, a comprehensive study on evaluation of polymorphisms of above genes was carried out in 1139 OSCC male cases and 1470 general males. A significant effect of AQ chewing or AQ chewing combined with cigarette smoking or alcohol drinking on the risk of OSCC was observed. GSTT1 null genotype was significantly associated with an increased risk of OSCC (odds ratio (OR), 2.10; 95% confidence interval (CI), 1.64-2.68, p = 0.000000003). After adjustment for cigarette smoking, AQ chewing and alcohol drinking, GSTT1 null-type variant was still significantly associated with an increased risk of OSCC (OR= 2.00; 95% CI, 1.42-2.81, p = 0.00007), while GSTM1 was not associated with OSCC risk. Polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu, APE1 T-656G, MUTYh Gln324His, WRN Cys1367Arg, and XRCC1 Arg399Gln were not associated with OSCC risk in general. However, stratification analysis indicated that polymorphisms of APE1 Asp148Glu and MUTYh Gln324His were associated with OSCC risk in individuals with cigarette smoking combined with AQ chewing. Furthermore, those individuals with either APE1 148 Asp/Asp or MUTYh 324 His/His genotype had an increased OSCC risks when compared to those with APE1 148 Glu and MUTYh 324 Gln allele (OR = 1.48; 95% CI, 1.13-1.95, p = 0.005). In conclusion, our results demonstrated that polymorphisms of genes involved in detoxification and BER of oxidative stress could influence the OSCC risk especially for those have history of cigarette smoking and AQ chewing.
Citation Format: Chih-Hsiung Lai, Li-Ling Chiu, Huei-Tzu Chien, Saou-Hsing Liou, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Ling-Ling Hsieh. Polymorphisms of GSTT1, APE1 and MUTYh gene and the risk of oral 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 4146. doi:10.1158/1538-7445.AM2014-4146
Abstract 4150: Nicotine dependence impacts the relationship between genetic variants and risk of lung adenocarcinoma
Authors: Tseng Tung-Sung , Park Jong Y. , Zabaleta Jovanny , Moody-Thomas Sarah , Sothern Melinda S. , Chen Ted , Lin Hui-Yi 
Published: May 2015

Abstract
Lung cancer, the leading cause of cancer death, accounted for 27% of cancer deaths for Americans in 2013. Despite its negative impact on public health, effective early detection tools for lung cancer are still under development. Several genetic variations associated with lung cancer risk and smoking behavior have been identified in some genome-wide association studies. It is unclear, however, if the gene variants affect lung cancer risk directly or indirectly through nicotine dependence. In an attempt to elucidate the relationships between lung cancer, genetic variants and smoking, we applied mediation analysis to quantify the impact of nicotine dependence. We evaluated 37 single nucleotide polymorphisms (SNPs) in nine candidate genes (TERT, CLPTM1L, CHRNB3, CHRNA6, CHRNA5/A3/B4, CYP1A1, and TP53), previously reported to be associated with lung cancer risk or with smoking behavior. A total of 661 lung adenocarcinoma (ADC) cases and 1,347 controls with a smoking history obtained from the Environment and Genetics in Lung Cancer Etiology (EAGLE) case-control study were included in the study. Results show that nicotine dependence is a mediator of the association between lung ADC and gene variations of CHRNA3 and CHRNB4 and accounts for approximately 20% of this relationship. The association between two CHRNA3 SNPs (rs1051730 and rs12914385) and risk for lung ADC reached a genome-wide significance (p-value=1.9x10-10 and 1.1x10-10, respectively). Also, these two SNPs had the most significant indirect effect on lung ADC risk through nicotine dependence (p=7x10-5 and 3x10-4). Gene variations rs2736100 and rs2853676 in TERT and rs401681 and rs31489 in CLPTM1L had a significant direct association on lung ADC without an indirect effect through nicotine dependence. In addition, rs6474414 in CHRNB3 and rs4646421 in CYP1A1, were associated with nicotine dependence but not directly with lung ADC risk. Our findings provide valuable information for understanding the pathogenesis and for developing potentially effective screening tools for lung ADC. These identified SNPs may improve prediction accuracy of lung ADC at earlier stages, which is essential to enhancing survival rates. Translating these findings into public health practice may lead to tailored and customized smoking cessation interventions for Individuals with genetic variants, which have both direct and indirect effect through nicotine dependence on lung ADC.
Citation Format: Tung-Sung Tseng, Jong Y. Park, Jovanny Zabaleta, Sarah Moody-Thomas, Melinda S. Sothern, Ted Chen, Hui-Yi Lin. Nicotine dependence impacts the relationship between genetic variants and risk of lung adenocarcinoma. [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 4150. doi:10.1158/1538-7445.AM2014-4150
Abstract 4153: Global African ancestry is not associated with lung cancer survival
Authors: Iverson Carissa C. , Fletcher Sarah , Blume Jeffery , Dilks Holli , Chen Heidi , Deppen Stephen A. , Bush William S. , Crawford Dana C. , Blot William J. , Grogan Eric L. , Aldrich Melinda C. 
Published: May 2015

Abstract
Lung cancer is the leading cause of cancer-related mortality among men and women in the United States, accounting for 27% of all cancer-related deaths. Blacks experience poorer 5-year survival compared to whites. We hypothesized that individuals with higher global African ancestry have poorer survival compared to individuals with lower global African ancestry. We identified incident non-small cell lung cancer cases in the Southern Community Cohort Study (SCCS), a prospective study of low-income adults recruited from across the Southeast region of the United States. Individuals who donated a biospecimen were genotyped using the Illumina Human Exome BeadChip, which contains a panel of ancestry informative markers (AIMs). After standard quality control, 398 individuals (262 self-reported black and 134 self-reported white) remained for analysis. Global ancestry was estimated from 2,604 AIMs using the software program ADMIXTURE. Self-reported blacks had a median global African ancestry of 88.12%, while the median global African ancestry in self-reported whites was less than 0.01%. We estimated hazard ratios and 95% confidence intervals using Cox proportional hazard models adjusted for age, sex, body mass index (BMI), cigarettes per day, disease stage, treatment, insurance coverage, family history of lung cancer and recruitment site. BMI, age, cigarettes per day and global African ancestry were modeled using restricted cubic splines. We estimated time dependent area under the curve (AUC) for our main effects model and a main effects model with interactions, both with and without genetic ancestry. We found that the main effects model had an average AUC of 0.81. When global African ancestry was excluded, the AUC was minimally reduced to 0.80. When interactions were added to the main effects model, the AUC increased to 0.88. Removal of global ancestry from the interactions model reduced the AUC to 0.84. In the main effects model, the two most predictive variables were stage and treatment with X2 values of 36.13 (degrees of freedom, df=2) and 15.47 (df=4), respectively. While we conclude that global African ancestry has little effect on overall survival, a relationship between global African ancestry and stage or treatment remains to be investigated.
Citation Format: Carissa C. Iverson, Sarah Fletcher, Jeffery Blume, Holli Dilks, Heidi Chen, Stephen A. Deppen, William S. Bush, Dana C. Crawford, William J. Blot, Eric L. Grogan, Melinda C. Aldrich. Global African ancestry is not associated with lung cancer survival. [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 4153. doi:10.1158/1538-7445.AM2014-4153
Abstract 4155: Genome-wide association study of survival in early stage non-small cell lung cancer
Authors: Ma Hongxia , Jin Guangfu , Hu Zhibin , Shen Hongbing 
Published: May 2015

Abstract
Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths all over the world. Studies have indicated that molecular biomarkers including genetic variants may provide additional values for the targeted treatments and clinical outcomes of NSCLC patients. In this study, we evaluated the associations between genome-wide genetic variants and the survival of NSCLC in a cohort of 365 early-stage NSCLC patients with surgery, and replicated sixteen promising loci in another independent cohort with 327 early-stage NSCLC patients in Chinese population. The results showed that rs10023113 in CAMK2D was consistently associated with survival of early-stage NSCLC in the GWAS scan and the replication cohort [GWAS scan: hazard ratio (HR) = 2.84; 95% confidence interval (CI) = 1.90-4.23, P = 1.29×10-6; replication cohort: HR = 2.19, 95% CI = 1.15-4.21, P = 1.80×10-2]. When combining all the patients, the results showed that the variant allele of rs10023113 was significantly associated with poor prognosis of NSCLC with P value reaching 3.40×10-7 (HR = 2.30, 95% CI = 1.67-3.17). These findings suggest that CAMK2D rs10023113 may be a potentially prognostic marker for overall survival of early-stage NSCLC patients in Chinese population.
Citation Format: Hongxia Ma, Guangfu Jin, Zhibin Hu, Hongbing Shen. Genome-wide association study of survival in early stage non-small cell lung 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 4155. doi:10.1158/1538-7445.AM2014-4155
Abstract 4163: Chemokine and cytokine levels among lung cancer cases responsive to HPV antigen stimulation
Authors: Scheurer Michael E. , Amirian E Susan , Porter Paul , Corry David B. 
Published: May 2015

Abstract
Purpose: Human papillomavirus (HPV), the causative agent for anogenital and certain head and neck cancers, has been detected in lung tumors, but its role as an etiologic agent for lung cancer remains controversial. The lung is often subjected to exogenous inflammatory insults, and patients with chronic lung inflammation have an increased risk for cancer. In addition to the genomic instability that can be caused by HPV oncoproteins, the immunomodulatory impacts of HPV infection may foster a pro-inflammatory state that increases lung cancer risk. We sought to identify such immunomodulatory effects by examining the differences in lymphocyte and cytokine/chemokine profiles between lung cancer cases and HPV-vaccinated healthy controls.
Methods: Peripheral blood mononuclear cells were isolated from 22 newly diagnosed lung cancer cases and 11 healthy controls who had prior exposure to HPV antigens (immunized with Gardasil). Cells were enumerated via a hemacytometer, and were exposed to media alone or to 3 doses of Gardasil for 20 hours as an HPV challenge. Interleukin (IL-) 4, IFN-γ, and IL-17A secreting cells were then quantified using enzyme linked immunocell spot (ELISpot) analysis. Individuals were categorized as HPV-responsive if the HPV challenge resulted in an increase in at least 2 types of secreting cells, compared to media-exposed cells. The Milliplex human cytokine detection kit was used to assess circulating levels of 38 key cytokines in the plasma of cases and controls. Cytokine levels among HPV-responsive and HPV-non-responsive cases were compared. Survival analysis was also conducted.
Results: All 11 HPV-vaccinated controls demonstrated an increase in cells secreting IFN-γ and IL-4. Of the 22 cases, 13 (59%) were classified as HPV-responsive, with 2 cases displaying an increase in IFN-γ and IL-4 secreting cells upon HPV challenge. Levels of TGF-α, IL-10, IL-3, IL-5, and IL-7 were significantly higher among HPV-responsive compared to non-responsive cases. Significant survival differences were also observed by HPV-responsiveness and cytokine levels.
Conclusions: HPV clearly has substantial effects on the host's systemic immune response. Our study may explain whether and how the pathogenic process differs between HPV-infected and -uninfected lung tumors.
Citation Format: Michael E. Scheurer, E Susan Amirian, Paul Porter, David B. Corry. Chemokine and cytokine levels among lung cancer cases responsive to HPV antigen stimulation. [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 4163. doi:10.1158/1538-7445.AM2014-4163
Abstract 417: DNA methylation changes in Lynch syndrome and FAP-associated colorectal tumorigenesis
Authors: Valo Satu , Kaur Sippy , Ristimäki Ari , Renkonen-Sinisalo Laura , Järvinen Heikki , Mecklin Jukka-Pekka , Nyström Minna , Peltomäki Päivi 
Published: May 2015

Abstract
Colorectal cancer (CRC) develops via multiple steps which involve genetic changes, such as mutations in growth-regulatory genes, and epigenetic alterations, such as CpG island hypermethylation. These changes accumulate over time in the normal tissue, for example due to many environmental factors such as diet, and may result in pre-cancerous field defects. Genes having high level of methylation in peritumoral tissues could be used as biomarkers for colorectal carcinogenesis.
The most common familial cancer susceptibility syndromes are familial adenomatous polyposis (FAP), caused by inherited mutations in the APC tumor suppressor gene, and Lynch syndrome (LS), associated with inherited defects of the DNA mismatch repair (MMR) genes which together with other genetic and epigenetic changes are known to accelerate tumorigenesis. This investigation was designed to define how CpG island methylation of CRC risk genes varies in pre-cancerous and cancerous lesions, adjacent normal mucosa and distinct normal mucosa from genetically predisposed individuals.
Colonic mucosa biopsies from different colorectal regions were gathered from 40 Finnish LS mutation carriers and 23 FAP patients during regular surveillance. In addition with normal mucosa biopsies, all adenoma and carcinoma findings from these individuals together with matching normals were gathered and analyzed. Patient information was obtained from the nation-wide registry. CpG island methylation was studied with the methylation-specific multiplex ligation-dependent probe amplification test (MS-MLPA) which detects CpG methylation of selected genes. Immunohistochemistry was used to detect MMR protein expression in neoplastic lesions.
Of 16 CRC risk genes tested so far 9 show increased methylation in polyps/adenomas/carcinomas. Mean methylation values increase along with age in both syndromes, with polyps from LS showing the highest proportional increase relative to normal tissues. The results offer new insights to the molecular mechanisms through which DNA methylation can affect colorectal carcinogenesis in LS and FAP mutation carriers.
Citation Format: Satu Valo, Sippy Kaur, Ari Ristimäki, Laura Renkonen-Sinisalo, Heikki Järvinen, Jukka-Pekka Mecklin, Minna Nyström, Päivi Peltomäki. DNA methylation changes in Lynch syndrome and FAP-associated colorectal tumorigenesis. [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 417. doi:10.1158/1538-7445.AM2014-417
Abstract 4174: An integrative genomic analysis for clinically relevant cancer genetic aberration and targeted therapeutic prediction
Authors: Lee HoJoon , Ji Hanlee P. 
Published: May 2015

Abstract
While the genomic and genetic basis of many cancers has been partly elucidated, less is known about the identity of specific cancer genes that are associated with clinical parameters such as clinical stage, metastasis, and survival. To address this question, we compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data for twelve different cancers in the Cancer Genome Atlas Project. We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical parameters in each cancer type. To facilitate the identification of clinically actionable genetic aberrations from this cancer genomic data, we utilized genomic and drug response data from the Cancer Cell Line Encyclopedia (CCLE). These expansive data sets of hundreds of cancer cell lines include three genomic data types (mutations, copy number alterations, gene expression) and drug response data. To demonstrate the performance and validity of this approach, we demonstrated that our bioinformatics pipeline successfully identified i) synthetic genes that have their CNVs perfectly associated with stages from a simulated data ii) mutations of TGFBR2, methylation of MLH1 and other driver genes that have genetic changes associated with colorectal cancer (CRC) that demonstrate microsatellite instability CRC from TCGA data, and iii) IDH1 that obtained mutations associated with survival according to glioblastoma (GBM) data. We identify the top ranked genes that delineate key clinical features such as survival analysis or clinical stages for 13 cancers. A fit of the elastic-net regularized regression to more than 200 samples/cancer type and integrative analysis of integrative genomic platforms identified the set of top gene predictors of clinical parameters (TCGA data) and drug response (CCLE data). There are several genes ranked top in multiple cancer types while most of them are unique to a cancer type. These results provide us with new insights into the underlying genetic similarities and differences among 13 cancers; namely, common genetic characteristics that have implications for clinical phenotype. Finally, we are identifying the core set of gene aberrations that are both clinically relevant and drug responsible.
Citation Format: HoJoon Lee, Hanlee P. Ji. An integrative genomic analysis for clinically relevant cancer genetic aberration and targeted therapeutic prediction. [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 4174. doi:10.1158/1538-7445.AM2014-4174
Abstract 4178: Global assessment of the protein tyrosine phosphatome in cancer
Authors: Tonks Nicholas , Lucito Robert 
Published: May 2015

Abstract
Receptor tyrosine kinases and non-receptor tyrosine kinases are an important class of molecules controlling a large number of processes from growth to metabolic regulation. These tyrosine kinases have been well studied and scrutinized for their role in these normal processes as well as abnormal processes, such as cancer. Parallel to these kinases are more that 100 tyrosine phosphatases, which also fall into either receptor or non receptor classifications. While some of these phosphatases antagonize the tyrosine kinases others including many of the receptor bound phosphatases are critical in their own right in signaling processes such as pro survival, proliferation, etc. Although tyrosine kinases have been well studied, the study of tyrosine phosphatases has lagged. Numerous tyrosine phosphatases have been identified that are misregulated and important for cancer growth including PTPRD in breast cancer, and PTPRZ1 in small cell lung cancer as well as many others. However there has been no comprehensive study of all PTPs or the protein tyrosine phosphatome (PTPome), to identify which have a role in cancer. We as a cancer community are fortunate to have access to such a wide array of data types from a number of data sources such as TCGA, where we can determine if the PTPs are mis regulated in more than 20 types of cancers. We used TCGA data for all tumor types and subsetted the data to analyze the PTPome for all data types including expression, methylation, copy number and sequence data where available. Thus far we have identified known PTPs involved in a number of cancers, including PTPRD and PTPRZ1, but have also identified a number of PTPs altered in cancers that were less characterized such as the alteration of PTPRD in melanoma which is predominantly by mutations with much fewer deletions. While many of these mutations are missense and are difficult to characterize there are also a number of non-sense mutations, which would severely alter function as well as a number of splice site mutation of which some severely alter function and others are likely to alter function. The identification of this PTP is but one example to demonstrate the richness of this dataset. This analysis has been extremely useful to identify the PTPs that are altered in cancer and these results will be useful to many in the research community that are interested in PTP involvement in cancer but will also be of even greater use to those researchers who have not appreciated the vast importance of these under studied proteins.
Citation Format: Nicholas Tonks, Robert Lucito. Global assessment of the protein tyrosine phosphatome in 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 4178. doi:10.1158/1538-7445.AM2014-4178