bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5261: Indices of diet quality and risk of lung cancer incidence and mortality in the Women's Health Initiative Observational Study
Authors: Myneni Ajay A. , Giovino Gary A. , Millen Amy E. , LaMonte Michael J. , Wactawski-Wende Jean , Neuhouser Marian L. , Zhao Jiwei , Shikany James M. , Mu Lina 
Published: August 2018

Abstract
Background: Prospective evidence on the association between diet patterns and lung cancer risk is limited, particularly in older women. We investigated whether commonly used diet quality indices - Healthy Eating Index 2010 (HEI), Alternate Healthy Eating Index 2010 (AHEI), alternate Mediterranean Diet (aMED) and Dietary Approaches to Stop Hypertension (DASH) - were associated with lung cancer incidence and mortality in the Women's Health Initiative Observational Study (WHI OS).
Methods: Self-reported diet intake (food frequency questionnaires) and relevant covariate information was obtained from 86,090 race-ethnically diverse postmenopausal women aged 50-79 years at baseline (1993-1998). During a median follow-up of approximately 17 years, 1,491 lung cancer cases and 1,393 lung cancer deaths were documented. We used cox proportional hazards regression models to estimate hazards risks and 95% confidence intervals [HR (95% CI)] after controlling for age, race/ethnicity, education, body mass index, smoking, physical activity and energy intake.
Results and conclusions: Diet quality indices were not associated with lung cancer incidence overall but all four dietary indices showed a protective association (highest versus lowest quintile) against squamous cell carcinoma cases (12.8% of total lung cancer cases) [HEI: 0.56 (0.33-0.96), AHEI: 0.42 (0.24-0.76), aMED: 0.65 (0.39-1.08), DASH: 0.56 (0.32-0.97)]. Diet quality indices were not associated with lung cancer mortality overall or when stratified by histological type, except for HEI with lung cancer mortality overall [fourth versus lowest quintile: 0.82 (0.69-0.99)]. Smoking status did not modify the association between diet quality indices and lung cancer incidence or mortality. Further studies in other populations may help elucidate the relationship between diet patterns and lung cancer, especially by histological type.
Citation Format: Ajay A. Myneni, Gary A. Giovino, Amy E. Millen, Michael J. LaMonte, Jean Wactawski-Wende, Marian L. Neuhouser, Jiwei Zhao, James M. Shikany, Lina Mu. Indices of diet quality and risk of lung cancer incidence and mortality in the Women's Health Initiative Observational Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5261.
Abstract 5279: Prevalence and correlates of perceived harmfulness and addictiveness to traditional and alternative tobacco products among US adults
Authors: Mohammed Kahee A. , Schoen Martin W. , Osazuwa-Peters Nosayaba , Al-Taee Ahmad M. , Khneizer Gebran W. , Arnold Lauren D. , Hinyard Leslie , Burroughs Thomas E. 
Published: August 2018

Abstract
Purpose: Beliefs about addictiveness and harmfulness of tobacco products are associated with intentions to use them. This study aimed to (1) evaluate perceived harmfulness and addictiveness patterns towards multiple tobacco products and (2) examine sociodemographic variables that influence those perceptions.
Methods: Weighted multivariate ordinal logistic regression analyses were performed on 5,474 US adults aged ≥18 years who participated in the 2015 and 2017 cycles of the Health Information National Trends Survey-FDA. The two primary outcomes were perceived harmfulness and addictiveness of traditional (cigarette, cigar, and pipe filled with tobacco) vs alternative tobacco (e-cigarette, hookah, and “roll your own” cigarettes). All models were adjusted for age, gender, race/ethnicity, education, household income, census region, and smoking status.
Results: Overall, 7.9% of adults in the U.S. perceived alternative tobacco as “not harmful at all” compared to 2.4% for the traditional products. Similarly, 16.2% of adults perceived alternative tobacco as “not addictive at all” compared to 13.6% for the traditional products. Beliefs about the harmfulness and addictiveness of traditional and alternative tobacco products differed by sociodemographic characteristics and smoking status: Those who believed traditional and alternative tobacco products are more harmful were more likely to be female, older (compared with those aged 18-34), Black (compared with White), former or never smokers (compared with current smokers), and adults living in West (compared with Northeast). Similarly, those who believed traditional and alternative tobacco products are more addictive were more likely to be female, older, Black, and adults living in West. However, no association between smoking status and perceived addictiveness was noted.
Conclusion: Adults in U.S. perceive tobacco harmfulness and addictiveness differently based on their sociodemographic characteristics and smoking status. These findings are potential areas for targeted behavioral interventions to increase individuals' perceived risk of harm and addiction to all forms of tobacco products in the United States.
Citation Format: Kahee A. Mohammed, Martin W. Schoen, Nosayaba Osazuwa-Peters, Ahmad M. Al-Taee, Gebran W. Khneizer, Lauren D. Arnold, Leslie Hinyard, Thomas E. Burroughs. Prevalence and correlates of perceived harmfulness and addictiveness to traditional and alternative tobacco products among US adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5279.
Abstract 5285: Evaluation of a postpartum human papillomavirus vaccination program
Authors: Berenson Abbey B. , Hirth Jacqueline M. , Kuo Yong-Fang , Rupp Richard E. 
Published: August 2018

Abstract
Evaluation of a postpartum human papillomavirus vaccination program
Berenson AB, Hirth JM, Kuo YF, Rupp RE
Purpose: To evaluate the effectiveness of a large vaccination program which offers the human papillomavirus (HPV) vaccine to women during their postpartum hospitalization.
Methods: Based on the success of a pilot which offered the HPV vaccine to a select group of women, a postpartum HPV vaccination program was expanded in 2016 to include all eligible mothers who gave birth in a large Texas hospital serving low income women. Women from 23 different counties were included. With funding from the Cancer Prevention Research Institute of Texas (CPRIT), patient navigators were hired to identify and personally counsel all eligible women who met catch-up recommendation guidelines prior to their hospital discharge. Women were informed about the need and availability of the HPV vaccine during their hospitalization and offered it free of charge. Follow-up doses are coordinated with postpartum visits as well as well-baby visits in collaboration with the Department of Pediatrics. With Institutional Review Board approval, records of women who were approached during the first 11 months of the expanded program were reviewed to determine the number who chose to participate.
Results: Baseline HPV vaccination rates were low. A total of 1,782 postpartum women were counseled about the HPV vaccine of which 168 (9.4%) were already vaccinated and 5 others were ineligible. Of the remaining 1,609 women, 71.2% received a dose of the HPV vaccine during their hospitalization. The refusal rate among eligible women was 24%. Another 4.3% (n-76) agreed to get vaccinated, but were released from the hospital before the injection was given. Of these, 48 (63.2%) received the dose at a later clinic visit.
Conclusions: Offering the HPV vaccine as part of postpartum care can increase catch-up vaccination of young women who did not have the opportunity to be vaccinated at a younger age.
Citation Format: Abbey B. Berenson, Jacqueline M. Hirth, Yong-Fang Kuo, Richard E. Rupp. Evaluation of a postpartum human papillomavirus vaccination program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5285.
Abstract 5292: Visceral adiposity-stimulated genotoxicity and malignant transformation of epithelial cells
Authors: Chakraborty Debrup , Jdanov Vladislav , Benham Vanessa , Bullard Blair , Bernard Jamie J. 
Published: August 2018

Abstract
Obesity is a global epidemic with a predicted rate of 42% in the U.S.A by 2050. Epidemiologic studies show that obesity is a risk factor for developing cancer; however, the molecular mechanism has not been fully elucidated. Our published data demonstrate that fibroblast growth factor-2 (FGF2) released from fat cells (adipocytes) in the visceral adipose tissue (VAT) induces transformation/tumorigenicity in the skin and mammary epithelial cells. Specifically, FGF2 released from VAT stimulates epithelial cell growth in soft agar by inducing the proto-oncogene c-Myc. Growth in soft agar is a measure of transformation/tumorigenicity; neither transformation nor c-Myc induction in epithelial cells was reversible. c-Myc overexpression can initiate a process of genetic instability linked to tumor initiation. Our discovery of this novel direct path of VAT-stimulated tumorigenesis adds mechanistic insight to our earlier discovery that VAT secretions promote UVR-induced nonmelamoma skin cancer. The objective of our current study was to determine the mechanism by which FGF2 stimulates malignant transformation. We hypothesized that FGF2 from VAT induces c-Myc and subsequent genomic instability in epithelial cells, leading to increased carcinogenesis. To test hypothesis we generated a filtered conditioned-medium from the human VAT treated MCF-10A (mammary epithelial) and JB6 P+ (skin epithelial) cells and measured several downstream mediators of FGF2 and activation of FGFR-1 (FGF2 receptor). Following VAT treatment, epithelial cells demonstrated induced c-Myc protein expression along with ROS accumulation, elevated γ-H2AX foci, and increased micronucleus (MN) formation. We found that inhibition of c-Myc attenuated VAT-induced neoplastic transformation of MCF-10A and JB6 P+ cells, while constitutive activation of the c-Myc-induced spontaneous neoplastic transformation of JB6 P+ cells. Collectively, our data suggested FGF2 released from VAT interacts with FGFR-1 and activates c-Myc. The role of c-Myc in the formation of MN and DNA damage is under investigation. Determining the impact of excess VAT on cancer will lead to strategies to help prevent adiposity-associated cancers and identify individuals at risk for disease or individuals who may be susceptible to compounded genotoxicity due to DNA-damaging environmental exposures.
Citation Format: Debrup Chakraborty, Vladislav Jdanov, Vanessa Benham, Blair Bullard, Jamie J. Bernard. Visceral adiposity-stimulated genotoxicity and malignant transformation of epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5292.
Abstract 5307: Inferring parsimonious migration histories for metastatic cancers
Authors: El-Kebir Mohammed , Satas Gryte , Raphael Benjamin J. 
Published: August 2018

Abstract
Recent studies have attempted to infer the pattern of cellular migrations between a primary tumor and distant metastases using phylogenetic trees constructed from somatic mutations. Several of these studies have challenged the conventional view of monoclonal seeding of a metastasis, and reported complex patterns of migration between primary tumors and metastases, including polyclonal seeding and reseeding.
Most current analyses that attempt to infer migration patterns from somatic mutations rely on two key assumptions, sample homogeneity and mutation-migration concordance, that do not typically hold for cancer sequencing datasets. Consequently, standard phylogenetic analysis of mutations may result in incorrect or misleading patterns of metastasis.
We introduce a computational model to evaluate migration patterns in a rigorous manner. We use this model as a basis for Metastatic And Clonal History INtegrative Analysis (MACHINA), an algorithm that jointly infers parsimonious clone trees and migration histories of metastatic cancers from DNA sequencing data. We show that MACHINA accurately recovers clone trees and migration histories on simulated data. We apply MACHINA to sequencing data from metastatic ovarian, breast, prostate and skin cancer samples. In several cases, we find simpler migration histories than previously reported, and these alter conclusions regarding metastasis-to-metastasis spread, the anatomical site of the primary tumor, or the occurrence of polyclonal seeding and reseeding in individual patients. MACHINA enables researchers to rigorously assess the validity of different migration patterns in individual patients with metastatic disease and evaluate the prevalence of different migration patterns across large cohorts of patients and tumor types.
Citation Format: Mohammed El-Kebir, Gryte Satas, Benjamin J. Raphael. Inferring parsimonious migration histories for metastatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5307.
Abstract 5338: Comprehensive pan-cancer genomic analysis reveals link between 3'UTR DNA methylation and increased gene expression
Authors: McGuire Michael H. 
Published: August 2018

Abstract
Investigations into the function of non-promoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional regions (e.g. promoter, gene body, enhancer); however, the relationship between DNA methylation outside of the promoter region and gene expression in cancer requires further exploration. Through integrated analysis of gene expression and DNA methylation profiles (&gt;3,000 samples across multiple cancer types and corresponding normal tissues), we uncovered an enrichment of DNA methylation sites within the 3'UTR in which DNA methylation is strongly positively correlated with gene expression. In 5 of 10 tumor types examined, DNA methylation of the 3'UTR is associated with patient survival in a significant number of genes. Filtering for genes in which 3'UTR DNA methylation, relative to gene body DNA methylation, is more strongly correlated with gene expression yields a list of genes enriched for functions involving T cell activation. The immune checkpoint gene HAVCR2 (TIM-3) shows a substantial increase in 3'UTR DNA methylation, but not adjacent exonic/intronic, or promoter DNA methylation, upon T cell stimulation and upregulation of gene expression. Furthermore, this increase in HAVCR2 gene expression can be abrogated by treatment with demethylating agents. These findings implicate the 3'UTR as a functionally relevant DNA methylation site, particularly in regard to T cell activity. Additionally, they reveal a novel mechanism by which HAVCR2 is upregulated in T cells, providing a new means of targeting immune checkpoint blockade. Finally, these data offer a selective marker for choosing patients that could respond to the combination therapy of PD-1/PD-L1 inhibition and demethylating agents.
Citation Format: Michael H. McGuire. Comprehensive pan-cancer genomic analysis reveals link between 3'UTR DNA methylation and increased gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5338.
Abstract 5350: Single cell RNA-seq reveals transcriptionally distinct subpopulations within patient-derived pancreatic cancer organoids
Authors: Ray Mohana , Nandi Rajib K. , Calvo Isabel Romero , Kirby Kori , Weber Christopher , Kindler Hedy L. , Buschmann Mary , Roggin Kevin , White Kevin P. 
Published: August 2018

Abstract
Advances in 3D cell culture over the last decade have enabled the establishment of organoid models from a multitude of organs in varying stages of development and disease. Organoids recapitulate the tissue-specific cell types and exhibit similar morphology and spatial organization as the organ it is derived from. However, to the best of our knowledge, tumor organoids have never been profiled at a single cell level.
In this study, we applied Drop-seq, a high throughput single cell RNA-seq platform, to characterize the different cell types present in pancreatic cancer organoids. We sequenced the transcriptomes of 5494 single cells from organoids derived from a patient undergoing a Whipple procedure for pancreatic ductal adenocarcinoma (PDAC). We then developed a novel clustering approach based on a class of probabilistic generative models called topic models, leading to the identification of two subpopulations of cells. One subgroup expressed marker genes known to play important roles in PDAC biology, such as MUC1, CLDN4 and GAS5. Interestingly, this subgroup also bore markers for cancer stem cells (HES1 and SQSTM1) that have been found by multiple studies to mediate chemoresistance in PDAC. The other subpopulation differentially expressed AGR2 and TMBIM6, which are associated with endoplasmic reticulum (ER) stress and correlates with invasiveness of PDAC cell lines. Functional studies are underway to determine the exact role of these subgroups, but our preliminary findings are suggestive of a subpopulation of cells that maybe involved in resistance to chemotherapy. This is consistent with the clinical progression of this patient's cancer, suggesting that rapid, inexpensive single cell transcriptomics might provide more precise molecular information to personalized medicine programs than traditional RNA-seq alone.
Citation Format: Mohana Ray, Rajib K. Nandi, Isabel Romero Calvo, Kori Kirby, Christopher Weber, Hedy L. Kindler, Mary Buschmann, Kevin Roggin, Kevin P. White. Single cell RNA-seq reveals transcriptionally distinct subpopulations within patient-derived pancreatic cancer organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5350.
Abstract 5357: Mutational and transcriptomic profiling identify distinct angiogenic and inflammatory subtypes of angiosarcoma
Authors: Kim Jong Hyuk , Megquier Kate , Sarver Aaron L. , Thomas Rachael , Wang Chao , Elvers Ingegerd , Karlsson Elinor , Breen Matthew , Lindblad-Toh Kerstin , Modiano Jaime F. 
Published: August 2018

Abstract
Angiosarcoma is an aggressive, albeit rare cancer in humans. The cause of the vast majority of sporadic angiosarcomas is unknown, mortality is high, and no therapeutic targets have been identified to improve outcomes. Hemangiosarcoma (HSA) is a common cancer of dogs, and it shares histopathologic features with human angiosarcoma. In our previous work, canine HSAs were classified into angiogenic, inflammatory, and adipogenic subtypes based on transcriptional profiles. However, the genetic and molecular events that regulate transcriptional subtypes in angiosarcoma are not currently understood. Our goal was to use a comparative genomics approach to apply knowledge from appropriately powered canine studies to inform our research into human sarcomas. In this study, we identified recurrent mutations in RNASeq data from 93 HSAs and 16 nonmalignant controls, based on mutations first identified in exomes from 42 paired tumor and normal samples. In addition to identifying recurrent somatic mutations we also identified translocation fusions, allowing elucidation of oncogenic mechanisms for vascular endothelial growth factor receptors (VEGFR), phosphoinositide-3 kinase (PIK3) signaling pathways, and the p53 DNA damage repair pathway in canine HSA. Significantly, mutational signatures were associated with distinct molecular subtypes of canine hemangiosarcomas, and both the angiogenic and the inflammatory subtypes were apparent in RNASeq data from human angiosarcomas (n=14), suggesting that comparable etiologic mechanisms are operative in the canine and human disease. Our ongoing work seeks to understand how the molecular mechanisms give rise to molecular subtypes of angiosarcoma by defining the association between driver mutations, signaling pathway alterations and transcriptional patterns, which should allow us to identify rational therapeutic targets.
Citation Format: Jong Hyuk Kim, Kate Megquier, Aaron L. Sarver, Rachael Thomas, Chao Wang, Ingegerd Elvers, Elinor Karlsson, Matthew Breen, Kerstin Lindblad-Toh, Jaime F. Modiano. Mutational and transcriptomic profiling identify distinct angiogenic and inflammatory subtypes of angiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5357.
Abstract 5364: Somatic mutations in African American and non-Hispanic White young-onset colorectal cancers
Authors: Rozek Laura S. , Qin Tingting , Koeppe Erika , Ulintz Peter , Greenson Joel K. , Cote Michele L. , Stoffel Elean M. 
Published: August 2018

Abstract
The proportion of colorectal cancers (CRCs) diagnosed at age &lt;50 years is two-fold higher among African-Americans (AAs) compared to non-Hispanic Whites (NHW). Additionally, despite the rising incidence of young-onset CRC, little is known about the molecular characteristics of these as only 23 young-onset tumors were profiled in the TCGA cohort. Studies of CRC diagnosed in older individuals (age &gt;50) demonstrate that CRC tumors in AAs are more often right-sided and MMR proficient, with higher prevalence of KRAS mutations. Risk of death from CRC among AAs with MMR proficient tumors is 73% higher than for NHW, after adjusting for treatment and known prognostic factors. We analyzed archival FFPE CRC tumors diagnosed in individuals age &lt;50 (NHW enrolled in the UM Cancer Genetics Registry N=38 and African American subjects ascertained through the Wayne State University EpiCore N=13) for somatic mutations. Mutation profiling of tumor DNA from 51 CRCs diagnosed age &lt;50 was performed using NGS sequencing with multigene panels in 2 sets (Qiagen GeneRead Cancer panel of 124 genes [N=36 tumors], Qiagen Qiaseq Comprehensive Cancer Panel of 275 genes [15 tumors]). We observed differences in CRC somatic mutations by race and by age. There was marked heterogeneity among tumors with regard to numbers of somatic mutations, with an average of 659 (range 39-10,267) variants detected per tumor, with 19/51 (37%) tumors classified as hypermutated. Among the most frequently mutated genes in young CRC tumors were APC (98% of tumors), PIK3CA (92% of tumors), NOTCH2 (86% of tumors), PTCH1 (82%), BRCA2 (67%), BRCA1 (84%), HNF1A (100%), RAD50 (29%), POLE (27%), MSH6 (39%), and FGFR3 (39%). These mutation profiles differ markedly from those of TCGA older-onset, nonhypermutated tumors. We identified differences in somatic mutations by race, including mutations in PTEN (NHW: 21% vs. AA: 8%), TGFBR2 (NHW: 32% vs. AA: 15%), FBXW7 (NHW: 47% vs. AA: 8%), and KRAS (NHW: 45% vs. AA: 31%). The relatively high prevalence of hypermutated tumors in this racially diverse cohort highlights the critical gaps in knowledge about pathways involved in pathogenesis of young-onset CRCs and how genomic information could guide precision therapies.
Citation Format: Laura S. Rozek, Tingting Qin, Erika Koeppe, Peter Ulintz, Joel K. Greenson, Michele L. Cote, Elean M. Stoffel. Somatic mutations in African American and non-Hispanic White young-onset colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5364.