bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B90: Smoking prevalence among tobacco-related cancer survivors in the United States, BRFSS 2009
Authors: Underwood J. Michael , Fairley Temeika L. , Tai Eric
Published: January 2011

Introduction: Cancer survivors who continue to smoke are at increased risk for primary cancer recurrences or development of new malignancies. Risks may be even higher among Tobacco Related Cancer Survivors (TRCS). We provide a national report on smoking behavior among TRCS.

Methods: Tobacco-related cancers (lung/bronchial, pharyngeal, esophageal, stomach, pancreatic, kidney/renal, urinary bladder, cervical and leukemia) are defined according to the 2004 report of the Surgeon General on The Health Consequences of Smoking. Data from the 2009 Behavioral Risk Factor Surveillance System (BRFSS) were used to describe demographic characteristics and tobacco use behaviors reported by TRCS, other cancer survivors and the non cancer BRFSS cohort. Self reported prevalence percentages and confidence intervals were calculated using SAS version 9.2 (SAS Institute, Inc, Cary, North Carolina).

Results: Overall, 10% of BRFSS respondents reported being diagnosed with cancer. Approximately 17% of all cancer survivors were diagnosed with a tobacco related cancer. Survivors in this group were primarily white (85.4%) and female (71.9%). Approximately 8.8% of TRCS were Hispanic. TRCS report a substantially higher proportion of current and past tobacco use. Among TRCS, 68% (95%CI 66.0-69.0) reported a history of smoking and 27.1% (95%CI 25.4-28.9) reported currently smoking; among other cancer survivors, 45.7% (95%CI 45.4-45.9) reported a history of smoking and 27.6% (95%CI 27.3-27.9) reported currently smoking.

Conclusion: When compared to other cancer survivors, persons diagnosed with tobacco related cancers have higher past and current smoking rates. Smoking cessation interventions should target TRCS, and increased surveillance of smoking behaviors is needed in this population.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B90.
Abstract B95: Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort
Authors: Jacobs Eric J. , Newton Christina C. , Thun Michael J. , Gapstur Susan M.
Published: January 2011

Background: HMG-coA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Relatively little is known about the association between long-term statin use and incidence of most types of cancers.

Methods: We examined the association between use of cholesterol-lowering drugs, predominantly statins, and the incidence of 10 common cancers, as well as overall cancer incidence, among 133,255 participants (60,059 men and 73,196 women) in the Cancer Prevention Study II Nutrition Cohort during the period from 1997-2007. Multivariate Cox proportional hazards regression was used to estimate relative risks (RRs).

Results: Current use of cholesterol-lowering drugs for five or more years was not associated with overall cancer incidence (RR = 0.97, 95% CI = 0.92-1.03), or incidence of prostate, breast, colorectal, lung, bladder, renal cell, or pancreatic cancer, but was associated with lower risk of melanoma (RR = 0.81, 95% CI = 0.67-0.98), endometrial cancer (RR = 0.61, 95% CI = 0.42-0.90), and non-Hodgkin lymphoma (NHL) (RR = 0.73, 95% CI = 0.61-0.87).

Conclusion: These results suggest that long-term use of statins is unlikely to substantially increase or decrease overall cancer risk. However, associations between long-term statin use and risk of endometrial cancer, melanoma, and NHL deserve further investigation.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B95.
Abstract B98: Association between alcohol consumption and colorectal carcinogenesis: An ecologic study in Korea
Authors: Kim Jeongseon , Cho Young Ae
Published: January 2011

Background and Aim: The sharp increase in the incidence rate of colorectal cancer in Korea over the past decades may be partly attributed to the increase in alcohol consumption. An ecologic study was conducted in Korea to determine the association between alcohol consumption and the risk of colorectal cancer.

Methods: We obtained the colorectal cancer incidence rates (1999–2007) from the Korea National Statistics Office and data on national alcohol consumption (1998–2007) from the reports of the Korea National Health and Nutrition Examination Survey. Pearson's correlation coefficients were determined using the data of alcohol intakes and colorectal cancer incidence rate. People who consumed more than 45 g alcohol/day were defined as heavy drinkers.

Results: A significant correlation between alcohol consumption and the risk of colorectal cancer was observed in men; Pearson's correlation coefficients were statistically significant for men (r = 0.99; P = 0.001), but not for women (r = 0.82; P = 0.180). In the <50-year age group, the age-specific incidence rate for men was comparable to that for women, but in the ≥50-year age group, it increased rapidly in men. The increase in alcohol consumption appears to be attributable to increase in the number of heavy drinkers among men aged 25–59 years, particularly among men aged 45–49 years.

Conclusion: Alcohol consumption may be positively related to the incidence of colorectal cancer. Our findings may aid in predicting future colorectal cancer incidence in Korea.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B98.
Abstract CN01-03: Immunotherapy of established lesions caused by high-risk HPV
Authors: Melief Cornelis J.M , Welters M. J.P. , Valentijn A. R.P.M. , Meer T. M.A. Berends-van der , Lowik M. J.G. , Vloon A. P.G. , Essahsah F. , Fathers L. M. , Offringa R. , Drifhout J. W. , Oostendorp J. , Fleuren G. J. , Burg S. H. van der , Kenter G. G.
Published: January 2011

Therapeutic vaccination with a synthetic long peptide (SLP@) vaccine mediated the eradication of established human papillomavirus type 16 (HPV16)-positive tumors in mice and controlled wart growth and latent virus infection in rabbits persistently infected with cottontail rabbit papillomavirus. Subsequent phase I/II studies with an HPV16 SLP@ vaccine, consisting of 13 long peptides covering the HPV16 E6 and E7 antigens, in patients with advanced HPV16-positive cervical cancer, revealed that this vaccine was safe and highly immunogenic. The purpose of the current study was to test the clinical efficacy of this HPV16 SLP@ vaccine in HPV16-induced high-grade vulvar intraepithelial neoplasia (VIN3), a premalignant epithelial disorder, spontaneous regression of which occurs in less than 2% of patients and in which recurrence after standard treatment is high.

In a phase 2 trial, 20 women with VIN3 were vaccinated three times sc in the limbs with a mix of the HPV16 E6 and E7 synthetic long peptides formulated in Montanide ISA-51. The endpoints were objective clinical responses, defined as reduction of at least 50% in lesion size (partial response) or complete regressions, and HPV16-specific T-cell responses, determined before and after vaccination.

The vaccine was safe, as no side effects exceeding CTC grade 2 were observed. At 3 and 12 months after the last vaccination an objective response was observed in 12/20 (60%) and 15/19 (79%) patients respectively. Nine of them showed a complete and durable regression of the lesions at 12 months and at 24 months. The strength of the vaccine-induced HPV16-specific T-cell response was significantly higher in the group of patients with a complete regression of their lesions as compared to nonresponders.

This study shows that in women with VIN3 objective clinical responses can be achieved by therapeutic vaccination with synthetic long peptides that is able to induce effective HVP16-specific T-cell responses.

Literature:

1. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Essahsah F, Fathers LM, Drijfhout JW, Offringa R,Wafelman AR, Oostendorp J, Fleuren GJ, Burg van der SH, Melief CJ. Vaccination against Human Papillomavirus 16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med. 2009 Nov 5;361(19):1838-47.

2. Melief CJ, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer. 2008 May;8(5):351-60.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN01-03.
Abstract CN01-04: HBV vaccination to prevent hepatocellular carcinoma
Authors: Chang Mei-Hwei
Published: January 2011

Chronic HBV infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCC is one of the five major cancers in the world population. Hepatitis B virus (HBV) is the most important etiologic agent of liver cancer in the world population, particularly in areas highly prevalent for liver cancer.

Taiwan has launched the world's first universal HBV vaccination program in July 1984. The prevalence of HBV infection in vaccinated birth cohorts have been reduced remarkably to approximately one-tenth of the original prevalence. Furthermore, reduction of the HCC incidence in the vaccinated birth cohorts aged 6-14 years have been demonstrated. Recently, we have further provided evidence that the effect of HCC prevention by HBV vaccination has been extended from childhood to adolescent and gradually into early adulthood. The incidence of HCC was significantly lower among children and adolescents aged 6-19 years in the vaccinated than unvaccinated birth cohorts, showing an age- and sex-adjusted relative risk of 0.31 for the population vaccinated since birth.

Failure to prevent HCC results mostly from unsuccessful control of HBV infection by highly infectious mothers. The risk of developing HCC for vaccinated cohorts was statistically significantly associated with prenatal maternal HBsAg and HBeAg seropositivity; lack of administration of hepatitis B immunoglobulin at birth, and incomplete HBV vaccination. Future strategies to interrupt mother-to-infant transmission and to increase the global coverage rate of HBV immunization may enhance the cancer prevention effect of HBV immunization.

In conclusion, prevention of chronic HBV infection can successfully reduce the incidence of liver cancer. This is the first example of cancer preventive vaccine in human, which proves that prevention of the infection of an infectious agent can prevent its related cancer. This example has been extended to the prevention of cervical cancers, and hopefully into other infection-related cancers in the near future.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN01-04.
Abstract CN02-06: Phase IIB study to evaluate the safety and efficacy of topical difluoromethylornithine and topical diclofenac in the treatment of sun-damaged skin
Authors: Jeter Joanne M. , Stratton Steven , Einspahr Janine , Curiel Clara , Warneke James , Hu Chengcheng , Bartels Peter , Alberts David
Published: January 2011

Difluoromethylornithine (DFMO) and nonsteroidal anti-inflammatory drugs have been shown to have a synergistic protective effect against colon cancer. As single agents, both DFMO and diclofenac have demonstrated efficacy in the treatment of actinic keratoses, the cutaneous precursors to cutaneous squamous cell carcinomas. We designed a study investigating the effects of these two medications, alone and in combination, on sun-damaged skin of the forearm. The primary objective is to determine whether a three-month course of combination therapy increases the efficacy over either agent used alone in the treatment of moderately sun-damaged skin. The primary endpoint is the change in karyometric values from skin biopsies before and after treatment. A total of 156 subjects were enrolled in the study and randomized to A: topical DFMO applied BID × 90 days; B: topical diclofenac applied QD × 90 days; or C: topical DFMO applied BID and topical diclofenac applied QD × 90 days. Planned sample size was 138 evaluable subjects to provide 80% power to detect the difference in response rate as measured by karyometric average nuclear abnormality (ANA) between the single-agent DFMO arm and the combination treatment arm at the 2.5% significance level. The results for efficacy and safety will be presented at the AACR Frontiers in Cancer Prevention meeting. Secondary biomarker and clinical endpoints will also be summarized. These findings will provide insight into the potential use of the combination of these medications as skin cancer chemopreventive agents.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN02-06.
Abstract CN08-03: Breast cancer prevention: Predictors and outcomes of patient decision making
Authors: O'Neill Suzanne
Published: January 2011

Several options exist for breast cancer risk-reduction in women at moderate to high risk for the disease. However, cancer risk management decisions can be difficult. This is partially due to the competing risks, benefits and limitations of each management option, as well as related cognitive and emotional factors. This presentation draws on behavioral and decision-making research to detail risk management decision outcomes in the literature to date, examining reasons women may choose certain management options over others and why some options, such as uptake of chemoprevention, have not have taken hold in this population at rates previously expected. Data demonstrating the decisions made by women who receive BRCA1/2 test results and other women at moderate to high risk of the disease, including risk-reducing surgeries, screening, chemoprevention, and diet and physical activity will be presented. Potential cognitive and emotional variables related to decision outcomes will be reviewed. The talk will conclude with discussion of future research needs regarding decision support for current risk management options, as well as consideration of cognitive and emotional factors that may impact new risk management options currently on the horizon.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN08-03.
Abstract CN12-04: The role of inflammation and stromal cells in gastrointestinal cancers
Authors: Wang Timothy C. , Worthley Daniel , Tu Shuiping Tu , Quante Michael
Published: January 2011

Most gastrointestinal cancers arise in the setting of chronic inflammation, but which leads to the recruitment of additional stromal cells, but the nature of these cells have not been well-defined. Carcinoma-associated fibroblasts (CAFs) that express alpha-smooth-muscle-actin (αSMA+) are thought to contribute to cancer progression but their precise origin has not been established. We have employed IL-1β transgenic mice and Helicobacter felis-infected mice that develop gastric dysplasia and cancer to investigate the origins and contributions of CAFs. These studies suggest that chronic inflammation of the GI tract, along with other carcinogenic stimuli, results in remodeling of the bone marrow and recruitment of bone marrow-derived cells to the incipient cancer site. At least 20% of CAFs originate from BM cells, and BM-derived CAFs promote tumor growth in organotypic and xenograft models. Thus, BM-derived fibroblastic cells create a new cancer niche that contributes to the progression of cancer, and as such represent a potential target for cancer prevention therapy.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN12-04.
Abstract CN14-02: Motivating individual behavior change through theory-driven community engagement
Authors: Logan Henrietta L.
Published: January 2011

Community-based interventions built on a strong theoretical framework are relatively rare in oral health disparity research. It is assumed that community-based research should engage the community but less frequently is it expected that the interventions are designed to expose and test the mechanisms through which behavior changes. A first step in such a paradigm is a thorough understanding of the target behavior and the associated physical and social environment and the interaction thereof. This presentation will discuss the use of the Theory of Planned Behavior and the Elaboration Likelihood Model to design and test community-based interventions aimed at changing behavior associated with late stage diagnosis of head and neck cancer. Consideration will be given to elucidating the pathways through which behavior change occurs.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN14-02.
Abstract CN14-04: Identifying the premalignant lesion at high risk for progression to cancer
Authors: Mao Li
Published: January 2011

Oral tumorigenesis is a multistep process requiring the accumulation of multiple molecular alterations such as mutations, genomic deletions and amplifications, as well as epigenetic modifications in oral epithelial cells. These alterations allow the affected cells gaining growth advantages over other cells and other malignant phenotypes.

In the past two decades, extensive studies have been conducted to understand molecular abnormalities in oral cancers and oral premalignant lesions (OPLs). Although promising, none of these has translated into a clinical test which can improve patient classification or cancer risk assessment. OPLs can exhibit a variety of histological features from hyperkeratosis, hyperplasia, and mild dysplasia to severe dysplasia. Together with other clinical features, our current practice has limited capability to accurately stratify cancer risk of patients with OPL. Such stratification is critical in our effort to develop surveillance measures for early cancer diagnosis and interventions to prevent or delay cancer development. In this presentation, I will focus on a series of biomarker discovery studies based on patients with OPL and enrolled in a prospective chemoprevention trial to illustrate some of the current efforts in oral cancer risk assessment based underlying molecular abnormalities in OPLs.

The chemoprevention trial randomized 167 patients with biopsies obtained at the time of enrollment and certain time points during follow-up. One hundred and sixty-two patients had oral cancer-free survival data with the median time of follow-up about 7.5 years. During the follow-up period, 38 patients developed oral cancer but no statistically significant difference was observed in any of the treatment arms. We examined podoplanin expression, deltaNp63 expression, EGFR expression, EFGR copy numbers, global gene expression, and histopathologic features in OPLs from the patients obtained at either baseline or at 3 months follow-up. Potential roles of these factors in progression of OPLs and oral cancer risk were evaluated. Results suggest that these alterations may outperform previously reported biomarkers and clinicopathologic parameters in stratifying oral cancer risk of patients with OPLs.

Development of oral cancer risk assessment strategies faces a number of challenges. Etiologies of OPLs and oral cancer may change over time, such as the emerging evidence of HPV infection in orapharyngeal cancers. Populations tested in many of our studies may be biased and not representative of the general population. Therefore, results may be difficult to validate in independent populations. We lack of systematic research networks at the national level to facilitate oral cancer risk assessment, early detection, and prevention. Efforts are lacking to integrate oral cancer risk assessment and chemoprevention programs. Some progresses and thoughts towards these limitations will be discussed.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN14-04.
Abstract ED03-03: The clinical and biological impact of aberrant DNA methylation patterning in human cancer
Authors: Melnick Ari M.
Published: January 2011

Heritable gene regulatory information can be imparted through cytosine methylation of DNA and posttranslational modifications of histones and other chromatin proteins. These epigenetic instructions play a fundamental role in determining the phenotype of normal cells during tissue differentiation. Disruption of normal epigenetic programming plays an equally fundamental role in determining the phenotype of tumor cells in concert with genetic lesions, and is a hallmark of cancer. Aberrant distribution of cytosine methylation occurs in specific biologically and clinically relevant patterns in acute myeloblastic and lymphoblastic leukemias, and is particularly widespread in advanced stages of myelodysplasia. Both aberrant hypomethylation and hypermethylation appear to contribute to these abnormal patterns. Genomic analysis of aberrantly methylated genes provides clues towards which transcription factors direct gene expression in epigenetically defined leukemia subtypes. One difference between epigenetic and genetic lesions is that the former can be therapeutically erased or reprogrammed. Along these lines efforts to identify epigenetic biomarkers to guide epigenetic therapy has become of great interest, as has the development of novel drugs that target the various chromatin-modifying complexes. This presentation will explore state of the art data from various sources and discuss the biological and clinical significance, as well as therapeutic targeting of aberrant epigenetic programming in these diseases.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):ED03-03.
Abstract ED05-02: Common drugs associated with reduced cancer risk
Authors: Rennert Gad
Published: January 2011

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

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

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

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

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

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

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

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

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 >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 >90%). Analysis of the samples after randomly assigning them into testing and training sets also performed well (AUROC >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

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 <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.
Abstract PR-11: HPV vaccine adherence in urban youth
Authors: Tracy J. Kathleen , Terplan Mishka , Lydecker Alison D. , Schluterman Nicholas
Published: January 2011

Background: Human papillomavirus (HPV) is the most common sexually transmitted disease among adolescent females in the United States, with 29.5% of sexually active 14-19 year olds infected at any given time. Persistent infection with cancer causing types of HPV is also a necessary step in the cervical cancer carcinogenesis process. HPV vaccines have been licensed in the United States since 2006; however, relatively modest proportions of the vaccine-eligible population have elected to receive the HPV vaccine. Further, among those who initiate HPV vaccination, a majority fail to complete the three-dose regimen needed for maximum protection.

Methods: Data from the clinical data repository at the University of Maryland Medical Center was queried to identify women that initiated HPV vaccination between August 2006 (when UMMC began offering the HPV vaccine) and August 2010. Statistical analyses were conducted to assess vaccine adherence in the study population. The association of age and race with vaccination adherence was also assessed.

Results: During the time period of interest, 9,658 women potentially eligible women between 9-26 years were seen at the UMMC outpatient practices. Of those, 2,641 women (27.3% of the target group) initiated HPV vaccination. African-American women comprised 2/3 of those who initiated vaccination. Among those women that initiated vaccination, 39.1% completed a single dose, 30.1% completed 2 doses, and 30.78 completed the recommended 3-dose regimen. Age was related to vaccine adherence, with women 18 and older being least likely to complete more than a single dose (p=0.001). African-American women were less likely than Caucasian women to complete the three-dose regimen (p<0.001).

Conclusions: Despite strong efficacy data for the HPV vaccines, relatively small proportions of eligible women have elected to uptake the vaccine as primary prevention for cervical cancer. Further, of those who initiate vaccination, significant proportions fail to complete the recommended three-dose regimen. Young adult women are the least likely to complete the three-dose regimen as are women in minority groups. The public health consequence of this is that significant numbers of women remain unprotected or underprotected. Evidence-based interventions are needed to foster both vaccine uptake and adherence for optimal prevention cervical cancer. Interventions that address barriers for minority women and young adult women are needed. Technological innovations such as text messaging may offer an effective method to address these issues.

This talk is also presented as Poster B103.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-11.