bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ED05-02: Common drugs associated with reduced cancer risk
Authors: Rennert Gad 
Published: January 2011

Abstract
The list of commonly used medications thought possibly to be associated with a reduction in risk of cancer is constantly growing. Among these drugs are aspirin, NSAIDs, Cox-2 inhibitors, statins, bisphosphonates, HRT, levothyroxine, colchicin, allopurinol, and the antiglycemic drug metformin. Most of these medications show an association with risk reduction across different cancer sites; some are more specific to one type of cancer while others may reduce risk in one site and increase risk in another. Biological pathways of anticancer activity have been suggested for most of the abovementioned medications and relevant cancer biomarkers can support, but not prove, the suggested associations.
Most data on commonly used medications come from observational studies since most of these drugs have not been studied in randomized controlled trials (RCTs) with cancer as a predefined endpoint. Data from observational studies are prone to a variety of biases making their use problematic. Data from retrospective studies on medications used for a single clinical indication are also problematic as it is hard to separate the potential preventive effect of the drug from the possible association between the disease (for which the drug was given) and cancer. Most of these commonly used medications are off-patent and therefore there is no incentive for the pharmacological industry to test them in RCTs for anticancer effects. RCTs might also not be feasible for the study of widely used drugs, both because of the high risk of contamination of the control arm as well as the selectivity and nonrepresentativeness of the participants who are not already taking these medications. Well designed association studies combined with supporting biomarkers data might be the only source of evidence for decision making on this subject. Alternatively, whether such common drugs actually have cancer prevention effects might only be alluded to through a natural experiment where reduction in cancer incidence will occur concurrently with an increase in the use of these drugs.
The literature is full of conflicting reports on the association of medications with cancer risk. There are many factors that can contribute to this — differences in types of studies, in class of medication within a pharmacological group (for example simvastatin vs. atorvastatin), in dosage, length of use, mode of delivery (oral, IV, patch), or in type of population studied (genetic differences in drug metabolism). We the lack of RCT results, all of these elements need to be taken into account when trying to conduct a meta-analysis of the currently available data and to reach a conclusion regarding to the true cancer prevention qualities of the relevant medications.
While the current data are very promising, all of these pitfalls add to the difficulty in understanding the true association between commonly used medications and cancer risk and might delay their incorporation into routine clinical practice.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):ED05-02.
Abstract ED06-03: Colonic bacteria, inflammation, and colon cancer
Authors: Sears Cynthia L. 
Published: January 2011

Abstract
A clear intersection between the infectious diseases and oncology fields has emerged from our understanding that many cancers arise in the setting of chronic infection. Roughly one-third of cancers worldwide, particularly epithelial cancers, are associated with identified single microbial infections, leading to the conceptual paradigm that chronic infection with specific microbes cause these cancers independent of other components of the ambient microbial community. Among epithelial cancers, colon cancer is the second leading cancer killer of adults in the United States but specific microbial contributors have not yet been identified. Rather, we now understand that the colon is home to one of the most dense and diverse communities of bacteria in the body and that we are each remarkably unique in our bacterial makeup reinforcing the contrasting view that the microbial contribution to colon cancer pathogenesis may lie in the composition of the colon microbiome. This talk will explore the scientific data supporting differing paradigms for how the colonic flora may contribute to colon oncogenesis. Particular attention will be paid to specific, usually commensal, members of the colonic microbiome and the mechanisms by which they may initiate and/or promote colon tumors. A framework for utilizing this knowledge to better understand the pathogenesis of colon cancer and to develop new approaches to colon cancer prevention will be discussed.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):ED06-03.
Abstract PL01-06: Nicotine-dependence pharmacogenetics: Implications for personalized therapy
Authors: Schnoll Robert A. , Lerman Caryn 
Published: January 2011

Abstract
This summary outlines the evidence base for using a genetically informed biomarker to tailor smoking cessation treatment. This marker represents the rate of CYP2A6-mediated nicotine clearance, and is measured using the ratio of the nicotine metabolites derived from nicotine from smoking (3'hydroxycotinine [3HC]/cotinine), referred to as the nicotine metabolite ratio or NMR. The NMR has been associated retrospectively with the ability to quit smoking and differential response to nicotine dependence therapy in multiple independent clinical trials. We first examined the NMR in an open label trial of transdermal nicotine patch versus nicotine nasal spray. In the patch condition, slow metabolizers (the lowest quartile of the NMR) had significantly higher quit rates than normal metabolizers (2nd to 4th quartiles of the NMR) at the end of 8 weeks of treatment and at 6-month follow up, even after controlling for baseline cigarettes per day and level of nicotine dependence. No such relationship was observed among smokers who received nicotine nasal spray, presumably because they titrated their dose of treatment (and nicotine) based on their CYP2A6-mediated level of nicotine metabolism. Importantly, this relationship of pretreatment NMR (based on smoking) to quit rates with nicotine patch has been validated in an independent trial. Further, a double-blind trial of bupropion versus placebo established a significant NMR-by-treatment interaction; specifically, slow nicotine metabolizers had high quit rates on placebo, which were not enhanced further by the non-nicotine medication bupropion. In contrast, normal nicotine metabolizers performed poorly on placebo, but well on bupropion. Thus, convergent evidence across multiple independent clinical trials supports an association of the NMR with smoking cessation and response to treatments for nicotine dependence. These effects are significant beyond the effects of standard pretreatment clinical measures (e.g., baseline smoking rate, level of nicotine dependence). These data suggest that slow nicotine metabolizers respond well to placebo/behavioral counseling alone and benefit substantially from transdermal nicotine patch, whereas normal nicotine metabolizers achieve little benefit from behavioral counseling alone or nicotine patch, but respond well to non-nicotine medications. To translate these findings to clinical practice, we are initiating a large prospective stratified pharmacogenomic trial that will evaluate the use of the NMR to optimize treatments for nicotine dependence.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PL01-06.
Abstract PL03-07: Obesity and mTOR signaling
Authors: Thomas George 
Published: January 2011

Abstract
The recent epidemic in obesity is the chief cause of the dramatic increase in a number of associated pathologies including diabetes, hyperlipidemia, cardiovascular disease and, most recently, cancer. Moreover, it is the chief cause behind the explosion in healthcare costs and the disquieting observation that for the first time in decades, human lifespan is decreasing for North Americans. The role of diet in cancer is particularly pertinent in the United States, where more than 60% of adults have been diagnosed as either clinically overweight or obese. The generally accepted explanation for the striking increase in obesity is that, during evolution, the scarcity of food led to the development of dominant genetic traits that favor the securing and storage of calories, which are now accentuated by the increased availability, tastefulness, abundance, and relatively low cost of food. The link between obesity and cancer is not specific for any one cancer, but is applicable to a number of cancer types including breast, colon, and prostate. The specific role of diet in mediating these effects has been difficult to resolve through epidemiological studies because such data rely on estimations of food intake, food sources, and the appropriate time periods to include in the study. In addition, endpoints in epidemiological studies are limited to factors such as tumor incidence and mortality, and little can be learned about the underlying biochemical and cellular mechanisms. Such studies are best dissected at the cellular level, then integrated with mouse models to determine the impact of specific phenomenon on human cancer. Validation for such an approach has come from studies on caloric restriction, which has been noted for some time to blunt cancer progression. Initially it was thought that the effects of caloric restriction on tumor progression were a secondary response to decreased cell growth; however, it is now recognized that this process actually impinges on key intracellular signaling pathways, particularly that of the mammalian target of rapamycin complex-1 (mTORC1). In turn this pathway is opposed by a large tumor suppressor genes including phosphatase and tensin homolog (PTEN), tuberous sclerosis complex (TSC1/2), neurofibromin (NF1), LKB1, initiation factor 4E-binding protein (4E-BP1) and programmed cell death protein 4 (PDCD4). In our laboratory we have been particularly interested in the role of two key downstream effectors of mTORC1 in obesity and cancer: 4E-BP1 and 40S ribosomal protein S6 kinase 1 (S6K1). In this talk we will particularly focus on the role of these signaling components in mediating the effects of nutrient overload in obesity and cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PL03-07.
Abstract PL05-05: The Australian skin cancer prevention experience: Lessons learned and global challenges ahead
Authors: Sinclair Craig 
Published: January 2011

Abstract
Australia has one of the highest skin cancer incidence and mortality rates in the world. The reason for these high rates is due in part to the high ambient UV radiation levels, combined with a predominantly susceptible fair-skinned population.
To address this problem, since 1980, Australians have been exposed to social marketing campaigns like SunSmart to raise awareness of skin cancer prevention. These campaigns have used advocacy to influence legislative reforms and mass media alongside interventions in schools, workplaces, and in the community to motivate sun protective behavior.
As a result of these interventions it can be demonstrated that social marketing campaigns can be a very effective method to not only motivate behavior change, reduce sunburn, and increase awareness but more importantly, reduce melanoma rates. In addition to this, we have been able to demonstrate that for every $1 the government invests in skin cancer prevention over a 20-year period, it will yield a $2.30 return. This makes skin cancer control a remarkably good investment in public health. However, long-term investment in this area is required otherwise any population gains in behavior are very likely to be quickly eroded.
In more recent years, skin cancer prevention programs worldwide have faced significant challenges in particular from the sunbed industry as well as increased awareness by the general population of vitamin D and its potential positive health benefits.
To address these issues, Australia now has a comprehensive approach to manage sunbed operations that include legislative requirements to restrict under 18 access, ban people with skin type 1, and the licensing of operators. Due to these intervention and increased awareness, there has been a decrease of up to 50% in the number of sunbed operators in Australian cities, a downturn not seen anywhere else in the world.
In addition to this, considerable effort has gone into managing the issues associated with vitamin D to the point now where the SunSmart program is an authoritative voice to advise people when they should use sun protection, but also when they should not.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PL05-05.
Abstract PL05-06: Policy and environmental approaches to cancer prevention: The New York City experience
Authors: Farley Thomas A. 
Published: January 2011

Abstract
Much of the focus on cancer prevention has been on early detection and treatment, but much of the actual progress in reducing cancer mortality has resulted from primary prevention of unhealthy behaviors. Tobacco use, unhealthy diet, and physical inactivity are responsible for a large proportion of cancers in the United States. The New York City Department of Health and Mental Hygiene takes a population-based approach to cancer control, focusing on promoting healthy behaviors by changing the social and built environment.
This session will present examples of New York City's environmental approaches to cancer control and data on their effectiveness in a large, diverse urban population. The presenter will discuss the city's use of legislation and counter-advertising to reduce the number of adult and youth smokers, and will describe initiatives to decrease consumption of sugar-sweetened beverages and encourage physical activity.
Based on New York City's experience, public health agencies should expect industry opposition to initiatives that may have an impact on consumer behavior. To succeed, cancer prevention programs based on social and environmental change require involvement of state and local governments and benefit from strong public-private partnerships. Researchers interested in cancer prevention should conduct studies of the impact of policies and other population-based approaches to modifying behaviors that increase the risk of cancers.
Learning objectives: 1. Identify two environmental approaches to tobacco control. 2. Describe population-based methods to reduce consumption of sugar-sweetened beverages and increase physical activity. 3. Describe research questions relevant to policy approaches to primary prevention of cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PL05-06.
Abstract PR-02: STAT2 contributes to promotion of colorectal and skin carcinogenesis
Authors: Gamero Ana M. , Young Matthew R. , Mentor-Marcel Roycelynn , Bobe Gerd , Scarzello Anthony J. , Wise Jennifer , Colburn Nancy H. 
Published: January 2011

Abstract
STAT2 is an essential transcription factor in the type I interferon (IFN-α/β) signal transduction pathway and well described for its role in mediating antiviral immunity and cell growth inhibition. Unlike other members of the STAT family, STAT2 is unique as IFNs are the only cytokines known to date to induce its activation. Given the inflammatory and antiproliferative dual nature of IFNs, our initial hypothesis was that STAT2 prevents inflammation-induced colorectal and skin carcinogenesis by altering the inflammatory microenvironment. In contradiction to our hypothesis, deletion of STAT2 inhibited rather than promoted AOM/DSS-induced colorectal carcinogenesis as measured by prolonged survival, lower adenoma incidence, smaller polyps, and less chronic inflammation. This protective effect was not restricted to the colon as deletion of STAT2 also inhibited DMBA/TPA-induced skin carcinogenesis as indicated by reduced papilloma multiplicity. A potential mechanism by which STAT2 promotes carcinogenesis is through activation of proinflammatory mediators. Deletion of STAT2 decreased AOM/DSS-induced expression and release of proinflammatory mediators such as interleukin 6 and CCL2 and decreased interleukin-6 release from skin carcinoma cells, which in turn decreased STAT3 activation. Therefore, our findings identify STAT2 as a novel contributor to colorectal and skin carcinogenesis that may act to increase the gene expression and secretion of proinflammatory mediators, which then activate the oncogenic STAT3 signaling pathway.
This talk is also presented as Poster A27.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-02.
Abstract PR-04: Interactions between plasma levels of 25-hydroxyvitamin D and insulin-like growth factor (IGF)-1, IGF-binding proteins and C-peptide with risk of colorectal cancer
Authors: Wu Kana , Feskanich Diane , Fuchs Charles , Chan Andrew , Willett Walter , Hollis Bruce , Pollak Michael , Giovannucci Edward 
Published: January 2011

Abstract
Background: Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide (a marker of insulin exposure) have been implicated in colorectal carcinogenesis. However, IGF-1 is not an easily modifiable risk factor. Laboratory studies have suggested that 1,25-dihydroxyvitamin D3, the biologically active form of vitamin D may play a role in the regulation of IGFBP3, the major binding protein for IGF-1, suggesting that some of the cancer promoting effects of IGF-1 may be modified by vitamin D.
Methods: We examined additive and multiplicative interactions between plasma 25-hydroxyvitamin D (25(OH)D) levels and components of the IGF axis (IGF-1, IGFBP3, IGFBP1) as well as C-peptide levels combining data from two large U.S. cohorts, the Health Professionals Follow up Study (HPFS) and the Nurses’ Health Study cohort (NHS). 365 cases (NHS: 191 cases diagnosed between 1990-2000; HPFS: 174 cases diagnosed between 1993-2002) were matched to 727 controls by age, fasting status (NHS only) and month and year of blood donation. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.
Results: Individuals with high IGF-1/IGFBP-3 molar ratio, C-peptide levels, or low 25(OH)D levels were at elevated risk for colorectal cancer. Compared to participants with high plasma 25(OH)D levels and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF/IGFBP-3 ratio had an odds ratio (OR) of 1.38 (95% CI: 0.90 to 2.12) for colorectal cancer when 25(OH)D levels were high and an OR of 2.65 (95% CI: 1.74 to 4.04) when 25(OH)D levels were low (p(interaction): additive = 0.02, multiplicative = 0.25). Also, for colon cancer, among individuals with high C-peptide levels, risk was elevated when 25(OH)D levels were low (OR = 2.15, 95% CI: 1.26 to 3.65) but not when 25(OH)D levels were high (OR=1.08, 95% CI=0.63 to 1.85) (p(interaction); additive = 0.04; multiplicative = 0.18).
Conclusion: The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP3 ratio or C-peptide levels.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-04.
Abstract PR-06: Identification of age-dependent biomarkers for early detection of breast cancer using metabolite profiling: A multisite study
Authors: Asiago Vincent M. , Shanaiah Narasimhamurthy , Gowda Nagana G. , Owusu-Sarfo Kwadwo , Alvarado leiddy , Liu Lingyang , Heiligstedt Heather , Raftery Daniel 
Published: January 2011

Abstract
We report on our progress towards developing a test for early breast cancer detection using metabolite profiling methods. Using a combination of nuclear magnetic resonance (NMR) and multivariate statistical methods principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal signal correction-partial least squares-discriminant analysis (O-PLS-DA) to analyzed the metabolite profiles of 142 breast cancer patients and 272 healthy control from four different sites. PCA and PLS-DA analysis was able to distinguish cancer patients from controls. From the analysis of the corresponding loading plots, 17 metabolites that were altered in concentration between cancer and controls were identified and tested individually and collectively using all samples. From a variable selection analysis, nine metabolite markers were shortlisted from analysis of samples from two of the locations using 10-fold cross validation. A PLS-DA model built using these markers with leave one out cross validation provided a sensitivity of 84% and a specificity of 98% (AUROC &gt;0.95). Strikingly, when this model was used to test samples from the other two locations we achieved a sensitivity of 82% and specificity of 93% (AUROC &gt;90%). Analysis of the samples after randomly assigning them into testing and training sets also performed well (AUROC &gt;0.90). While additional work needs to be carried out on a broader range of normals and cancer patients, to the best of our knowledge, this is the first multisite study to identify and prevalidate a prediction model for early detection of breast cancer based on a metabolic profile. In particular, the combination of NMR and advanced multivariate analysis is a powerful approach for the early detection of breast cancer. This talk is also presented as Poster B20.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-06.
Abstract PR-09: Low-fat diet reduces NF-κB regulated inflammatory cytokines and angiogenic factors in plasma of men with prostate cancer
Authors: Heymach John V. , Shackleford Terry J. , Tran Hai T. , Yoo Suk-Young , Do Kim-Anh , Wergin Melanie , Saintigny Pierre , Vollmer Robin T. , Polascik Thomas J. , Snyder Denise C. , Ruffin Mack T. , Yan Shaoyu , Dewhirst Mark , Kunnamakara Ajai B. , Aggarwal Bharat B. , Demark-Wahnefried Wendy 
Published: January 2011

Abstract
Purpose: Diet and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain.
Procedure: We examined changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30 days. While two CAFS changed significantly in the FS arm (eotaxin and IL-16), 11 CAFs, including proangiogenic factors (vascular endothelial growth factor [VEGF], stromal-cell derived-1α) and myeloid factors (granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage-colony-stimulating factor) changed significantly in the LF arm compared to controls with virtually all of these factors decreasing.
Results: Significant decreases in body mass index occurred in the LF arms and correlated with VEGF decreases (P &lt;0.001). Most CAFs that changed in the LF arm are known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes. A trend toward reduced NF-κB, VEGF, carbonic anhydrase-IX, and cyclooxygenase-2 immunoreactivity was observed in resected prostate cancer specimens from the LF arm compared to controls.
Conclusions: Low-fat diets may reduce levels of specific inflammatory cytokines and angiogenic factors via the NF-κB mediated pathway.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-09.