Abstract CN10-03: Childhood obesity and leukemia: Opportunities for intervention
Obesity is a major contributor to cancer mortality, and is responsible for ~90,000 cancer deaths per year in the U.S. Part of this association can be attributed to the effect of obesity to increase cancer incidence, while obesity has been shown to worsen the outcome from a number of types of cancer. Retrospective studies have shown that obese children diagnosed with the high-risk form of the most common childhood cancer, acute lymphoblastic leukemia (HR-ALL) have a substantially higher risk of relapse than lean children.We have investigated these associations, generating laboratory models to investigate how obesity might i...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Mittelman, S. D. Tags: Diet and Cancer: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN10-02: Rare disorders informing cancer biology: Lessons learned from dyskeratosis congenita
This study includes comprehensive family history and individual history questionnaires, detailed medical record review, biospecimen collection, and evaluation at the NIH Clinical Center. In addition to the development of the diagnostic test, detailed clinical characterization of patients with DC and their families has led to improved understanding of the clinical consequences and management of DC and the spectrum of related telomere biology disorders. Through the use of genetic approaches ranging from linkage scans to whole exome sequencing, we have discovered three of the genetic causes of DC (TINF2, WRAP53, and RTEL1). A...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Savage, S. A. Tags: Other Topics in Cell, Molecular, and Tumor Biology: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN10-01: Tumor surveillance strategies in pediatric hereditary cancer predisposition syndromes
Cancer is the most common cause of disease-related death in children beyond the neonatal period. Primary prevention has not been commonly considered in the management of childhood cancers as ‘environmental’ agents have not generally been associated with cancer risk. Evidence from genetic and genomic studies supports a rapidly increasing role for inherited or de novo genetic alterations in the etiology of many childhood cancers. Diverse phenotypes have been associated with many of these gene alterations, and genotype:phenotype correlations continue to be defined. Some cancer predisposition syndromes are associat...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Malkin, D., Villani, A., Wasserman, J. Tags: Pediatric Malignancies: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN08-03: How does air pollution cause cancer?
In October 2013, the International Agency for Research on Cancer (IARC) evaluated outdoor air pollution and associated particulate matter (PM) as group 1 (known) human carcinogens for the lung and probable carcinogens for the bladder. Although the IARC monograph on outdoor air (Vol. 109) will not be published until late 2014, this talk reviews some of the main mechanistic data that supported this evaluation. The IARC working group consisted of four sub-groups: epidemiology, animal cancer, exposure, and mechanistic data. Six people comprised the mechanistic sub-group, and this talk is an overview of their review of the lite...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: DeMarini, D. M. Tags: Other Risk Factors: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN08-01: Air pollution and cancer: Implications of IARC's causal classification
This presentation will identify the main lessons learned from the extensive analysis and discussion of the carcinogenicity of outdoor air and describe potential areas for future research. The IARC classification of "outdoor air pollution" and "particulate matter air pollution" as carcinogenic to humans are based on a broad research foundation, but nonetheless there are important gaps to be addressed. For example, research is needed to understand more specifically the components of the air pollution mixture that drive cancer risk, in part to develop useful indicators for control and tracking. Further information is needed o...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Samet, J. M. Tags: Other Risk Factors: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN07-02: Obesity, inflammation, and breast cancer
Obesity is a risk factor for the development of several malignancies including hormone receptor–positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. Chronic inflammation increases the risk of multiple tumor types. A link between obesity, breast inflammation and hormone receptor-positive breast cancer was previously unknown. Obesity causes subclinical inflammation in visceral and subcutaneous white adipose tissue, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catal...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Dannenberg, A. J. Tags: Obesity, Metabolism, and Cancer: Oral Presentations - Invited Abstracts Source Type: research
Abstract PL06-03: Role of the circadian clock in skin cancer prevention and sunburn erythema
Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn apoptosis and erythema as a result of exposure to excessive UV light and damage to DNA confers an increased risk for melanoma and non-melanoma skin cancer. The early inflammatory response to UV exposure, sunburn, follows molecular and cellular responses including DNA repair and apoptosis. Previous reports have shown that nucleotide excision repair, the sole pathway for removing UV-induced DNA damage, as well as DNA replication, are regulated by the circadian clock in mouse skin. Furthermore, more skin carcinogenesis was observ...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Gaddameedhi, S., Sancar, A. Tags: Other Risk Factors: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN06-03: Disease dynamics: Cancers evolving fast and slow or not at all
This study found that BE that progressed to EA was characterized by punctuated chromosome instability with gains or losses of whole chromosomes or large regions of chromosomes that became significant 48 months before EA diagnosis followed by catastrophic genome doublings in the 24 months before cancer. In contrast, BE that did not progress to EA was largely characterized by somatic genomic "stasis" at the level of 1M SNP arrays for prolonged periods up to more than two decades. These results suggest a four year "window of opportunity" for early detection although future research may expand this window. These findings are s...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Reid, B. J. Tags: Other Topics in Biomarkers and Early Detection Research: Oral Presentations - Invited Abstracts Source Type: research
Abstract PL06-02: The clock in the cell
The circadian clock is an endogenous, cell-based timing mechanism. It has apparently evolved as a response to the highly predictable and metabolically challenging light/dark cycle. Circadian clocks are characterized as having a free running, circa 24h rhythm in constant conditions, an entrainment mechanism whereby those rhythms become exactly 24h, robustness, precision and compensation towards environmental variability such as temperature. While most of our knowledge concerning molecular mechanisms of the daily clock comes from the free running state, the clock is always found in the entrained state in nature. It is this p...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Merrow, M. Tags: Other Risk Factors: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN05-03: Cooperation between a rexinoid and EGFR-TKI for lung cancer prevention via Cyclin D1 destabilization
We previously reported that both nuclear retinoic acid receptor (RAR, retinoid) and retinoid X receptor (RXR, rexinoid) agonists can trigger proteasomal degradation of cyclins. This confers check point arrest and repair of carcinogenic DNA damage in bronchial epithelial cells. Mechanisms responsible for this induced degradation were discovered. These included ubiquitin-dependent as well as ISG15-dependent programs that independently destabilized expression of cyclin D1 and other G1 cyclin proteins. The critical receptor that confers this cyclin destabilization was RARβ. Yet, silencing of RARβ; and specifically of...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Dragnev, K. H., Memoli, V., Freemantle, S. J., Waxman, S., Dmitrovsky, E. Tags: Combinatorial Approaches to Chemoprevention: Oral Presentations - Invited Abstracts Source Type: research
Abstract PL05-02: Current therapies for diabetes - will they reduce cancer risk?
Type 2 diabetes has been associated with an increase in the incidence and mortality from many cancers. Understanding the mechanisms underlying Type 2 diabetes, has contributed to the discovery of the potential anti-cancer effects of diabetes treatments. Insulin resistance and hyperinsulinemia precede the development of hyperglycemia and Type 2 diabetes, and may be key factors contributing to the increased cancer risk. Other factors including hyperglycemia, steroid hormonal bioavailability (estrogen and testosterone), insulin-like growth factors, adipokines (leptin and adiponectin) and cytokines may also contribute to cance...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Gallagher, E. J. Tags: Metformin Prevention and Treatment Trials: Oral Presentations - Invited Abstracts Source Type: research
Abstract CN05-02: Exploiting aspirin's mechanism of action for combination chemoprevention
In human populations, aspirin has emerged as the agent with the most consistently observed chemopreventive effect on cancer, particularly of the colorectum. Remarkably consistent data demonstrating aspirin's efficacy have accumulated from prospective studies and randomized controlled trials conducted for the prevention of polyp recurrence, hereditary colorectal cancer, cardiovascular disease, and overall cancer. In addition, there are now convincing data supporting an association between aspirin use and lower risk of metastases and improved survival among colorectal cancer patients. This substantial evidence base has stimu...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Chan, A. T. Tags: Combinatorial Approaches to Chemoprevention: Oral Presentations - Invited Abstracts Source Type: research
Abstract PL05-01: Obesity, IGF-1 and cancer prevention: Mechanistic insights from transdisciplinary studies
The prevalence of obesity, an established risk and progression factor for many cancers, has more than doubled over the past three decades in the US, with ~36% of adults currently obese. The mechanisms underlying the obesity and cancer connection are becoming increasingly clear and reveal several potential targets and strategies for breaking the obesity-cancer link. We have established in multiple genetically engineered mouse models (GEMMs) of mammary, pancreatic and other epithelial cancers that diet-induced obesity (DIO) increases serum levels of bioavailable insulin-like growth factor (IGF)-1, induces insulin resistance,...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Hursting, S. D. Tags: Obesity, Metabolism, and Cancer: Oral Presentations - Invited Abstracts Source Type: research
Abstract PL04-03: Evidence for increased muscle breakdown associated with early pancreatic cancer
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression had not been studied. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from pancreatic cancer cases and matched controls from four prospective cohort studies. We found that elevated plasma levels of branched chain amino acids (BCAAs) are associated with a greater than 2–...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Heiden, M. G. V. Tags: Obesity, Metabolism, and Cancer: Oral Presentations - Invited Abstracts Source Type: research
Abstract PL04-02: ATM: Bridging DNA damage responses and metabolic regulation
Much of our understanding of the mechanisms involved in cellular DNA damage response pathways have come from studies of human cancer susceptibility syndromes. ATM, the gene mutated in the cancer-prone, radiosensitive disorder, Ataxia-telangiectasia (A-T), is a protein kinase that is a central mediator of responses to DNA double strand breaks in cells. Once activated, ATM phosphorylates numerous substrates in the cell that modulate the cell's response to the DNA damage. p53, one of the many targets of the ATM kinase, is a critical mediator of cell cycle changes and cell death signaling following DNA damage and other stresse...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Kastan, M. B., Valentin-Vega, Y., Brown, A., Scarbrough, P., Fleenor, D. Tags: Other Topics in Cell, Molecular, and Tumor Biology: Oral Presentations - Invited Abstracts Source Type: research
