Cancer Prevention Research

Our medical research library holds 7 studies published in Cancer Prevention Research (2008–2018). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 7 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: American Association for Cancer Research
• Published: 2008 to the present, United States
• Language: English
• ISSN: 1940-6207 (print), 1940-6215 (electronic)
• Its record in the NLM Catalog

2010s

• Methylation-derived Neutrophil-to-Lymphocyte Ratio and Lung Cancer Risk in Heavy Smokers. L. Grieshober, S. Graw, M.J. Barnett, et al. 2018;11(11):727-734. Randomized trial PubMed · Publisher · Free full text

  Abstract

  The neutrophil-to-lymphocyte ratio (NLR) is a biomarker that indicates systemic inflammation and can be estimated using array-based DNA methylation data as methylation-derived NLR (mdNLR). We assessed the relationship between prediagnosis mdNLR and lung cancer risk in a nested case-control study in the β-Carotene and Retinol Efficacy Trial (CARET) of individuals at high risk for lung cancer due to heavy smoking or substantial occupational asbestos exposure. We matched 319 incident lung cancer cases to controls based on age at blood draw, smoking, sex, race, asbestos, enrollment year, and time at risk. We computed mdNLR using the ratio of predicted granulocyte and lymphocyte proportions derived from DNA methylation signatures in whole blood collected prior to diagnosis (median 4.4 years in cases). Mean mdNLR was higher in cases than controls (2.06 vs. 1.86, P = 0.03). Conditional logistic regression models adjusted for potential confounders revealed a 21% increased risk of lung cancer per unit increase in mdNLR [OR 1.21; 95% confidence interval (CI) 1.01-1.45]. A 30% increased risk of non-small cell lung cancer (NSCLC) was observed for each unit increase in mdNLR (n = 240 pairs; OR 1.30, 95% CI, 1.03-1.63), and there was no statistically significant association between mdNLR and small-cell lung cancer risk. The mdNLR-NSCLC association was most pronounced in those with asbestos exposure (n = 42 male pairs; OR 3.39; 95% CI, 1.32-8.67). A better understanding of the role of mdNLR in lung cancer etiology may improve prevention and detection of lung cancer. Cancer Prev Res; 11(11); 727-34. ©2018 AACR.

  ©2018 American Association for Cancer Research.

• Inflammation-Related IL1β/IL1R Signaling Promotes the Development of Asbestos-Induced Malignant Mesothelioma. Y. Kadariya, C.W. Menges, J. Talarchek, et al. 2016;9(5):406-414. PubMed · Publisher · Free full text

  Abstract

  Exposure to asbestos is causally associated with the development of malignant mesothelioma, a cancer of cells lining the internal body cavities. Malignant mesothelioma is an aggressive cancer resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including malignant mesothelioma. The NALP3/NLRP3 inflammasome, including the component ASC, is thought to be an important mediator of inflammation in cells that sense extracellular insults, such as asbestos, and activate a signaling cascade resulting in release of mature IL1β and recruitment of inflammatory cells. To determine if inflammasome-mediated inflammation contributes to asbestos-induced malignant mesothelioma, we chronically exposed Asc-deficient mice and wild-type littermates to asbestos and evaluated differences in tumor incidence and latency. The Asc-deficient mice showed significantly delayed tumor onset and reduced malignant mesothelioma incidence compared with wild-type animals. We also tested whether inflammation-related release of IL1β contributes to tumor development in an accelerated mouse model of asbestos-induced malignant mesothelioma. Nf2(+/-);Cdkn2a(+/-) mice exposed to asbestos in the presence of anakinra, an IL1 receptor (IL1R) antagonist, showed a marked delay in the median time of malignant mesothelioma onset compared with similarly exposed mice given vehicle control (33.1 weeks vs. 22.6 weeks, respectively). Collectively, these studies provide evidence for a link between inflammation-related IL1β/IL1R signaling and the development of asbestos-induced malignant mesothelioma. Furthermore, these findings provide rationale for chemoprevention strategies targeting IL1β/IL1R signaling in high-risk, asbestos-exposed populations. Cancer Prev Res; 9(5); 406-14. ©2016 AACR.

  ©2016 American Association for Cancer Research.

• Targeting Inflammation in Cancer Prevention and Therapy. J. Todoric, L. Antonucci, M. Karin. 2016;9(12):895-905. Review PubMed · Publisher · Free full text

  Abstract

  Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immunosuppression, thereby providing a preferred background for tumor development. In clinical trials, lifestyle modifications including healthy diet, exercise, alcohol, and smoking cessation have proven effective in ameliorating inflammation and reducing the risk of cancer-related deaths. In addition, consumption of certain anti-inflammatory drugs, including aspirin, can significantly reduce cancer risk, suggesting that common nonsteroidal anti-inflammatory drugs (NSAID) and more specific COX2 inhibitors can be used in cancer prevention. In addition to being examined for their preventative potential, both NSAIDs and more potent anti-inflammatory antibody-based drugs need to be tested for their ability to augment the efficacy of more conventional therapeutic approaches on the basis of tumor resection, radiation, and cytotoxic chemicals. Cancer Prev Res; 9(12); 895-905. ©2016 AACR.

  ©2016 American Association for Cancer Research.

• Curcumin: a double hit on malignant mesothelioma. J.M. Miller, J.K. Thompson, M.B. MacPherson, et al. 2014;7(3):330-40. PubMed · Publisher · Free full text

  Abstract

  Inflammation is a key mediator in the development of malignant mesothelioma, which has a dismal prognosis and poor therapeutic strategies. Curcumin, a naturally occurring polyphenol in turmeric, has been shown to possess anticarcinogenic properties through its anti-inflammatory effects. Inflammasomes, a component of inflammation, control the activation of caspase-1 leading to pyroptosis and processing of proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the present study, we investigate the role of curcumin in pyroptotic cell death of malignant mesothelioma cells. Using in vitro models with mouse and human malignant mesothelioma cells, curcumin is shown to induce pyroptosis through activation of caspase-1 and increased release of high-mobility group box 1 (HMGB1) without processing of IL-1β and IL-18. Absence of IL-1β processing in response to curcumin-mediated caspase-1 activation is attributed to blockade of pro-IL-1β priming through inhibition of the NF-κB pathway. Furthermore, curcumin's cytotoxicity in malignant mesothelioma cells is demonstrated to be dependent on pyroptosis as inhibition of caspase-1 resulted in protection against curcumin-induced cell death. We also demonstrate that curcumin-mediated caspase-1 activation is oxidant dependent by using N-acetyl-L-cysteine (NAC) to inhibit pyroptosis. PCR array analysis using the human inflammasome template revealed that curcumin significantly downregulated levels of inflammasome-related gene expression involved in inflammation, e.g., NF-κB, toll-like receptors (TLR), and IL-1β. Our data indicate that curcumin has a double effect on malignant mesothelioma cells through induction of pyroptosis while subsequently protecting against inflammation.

• Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats. H. Nagai, Y. Okazaki, S.H. Chew, et al. 2013;6(11):1222-30. PubMed · Publisher

  Abstract

  Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction.

  ©2013 AACR.

• Intervening to reduce the future burden of occupational cancer in britain: what could work?. S. Hutchings, J.W. Cherrie, M. Van Tongeren, et al. 2012;5(10):1213-22. PubMed · Publisher

  Abstract

  In Britain, 14 carcinogenic agents and occupational circumstances currently account for 86% of estimated occupation attributable cancer. The future burden associated with these carcinogens has been forecast, using attributable fractions for forecast scenarios representing patterns of past and predicted future exposure, and exposure levels representing the introduction of new occupational exposure limits, increased levels of compliance with these limits and other reductions in worker exposure. Without intervention, occupational attributable cancers are forecast to remain at more than 10,000 by 2060. With modest intervention over 2,600, or with stricter interventions more than 8,200 cancers could be avoided by 2060 although because of long latency no impact will be seen until at least 10 years after intervention. Effective interventions assessed in this study include reducing workplace exposure limits and improving compliance with these limits. Cancers associated with asbestos, diesel engine exhaust, polycyclic aromatic hydrocarbons, work as a painter, radon, and solar radiation are forecast to continue, with construction remaining the prime industry of concern. Although exposure levels to the established carcinogens are falling, workers are remaining exposed at low levels at which there is still a cancer risk, although the aging population also contributes to rising cancer numbers, These forecasts can be used to assess the relative costs to society of different occupational carcinogenic agents, and the relative merits and savings associated with alternative intervention strategies. The methods are adaptable for different data circumstances, other types of interventions and could be extended to environmental carcinogens and other chronic diseases.

2000s

• Development and validation of a lung cancer risk prediction model for African-Americans. C.J. Etzel, S. Kachroo, M. Liu, et al. 2008;1(4):255-65. PubMed · Publisher · Free full text

  Abstract

  Because existing risk prediction models for lung cancer were developed in white populations, they may not be appropriate for predicting risk among African-Americans. Therefore, a need exists to construct and validate a risk prediction model for lung cancer that is specific to African-Americans. We analyzed data from 491 African-Americans with lung cancer and 497 matched African-American controls to identify specific risks and incorporate them into a multivariable risk model for lung cancer and estimate the 5-year absolute risk of lung cancer. We performed internal and external validations of the risk model using data on additional cases and controls from the same ongoing multiracial/ethnic lung cancer case-control study from which the model-building data were obtained as well as data from two different lung cancer studies in metropolitan Detroit, respectively. We also compared our African-American model with our previously developed risk prediction model for whites. The final risk model included smoking-related variables [smoking status, pack-years smoked, age at smoking cessation (former smokers), and number of years since smoking cessation (former smokers)], self-reported physician diagnoses of chronic obstructive pulmonary disease or hay fever, and exposures to asbestos or wood dusts. Our risk prediction model for African-Americans exhibited good discrimination [75% (95% confidence interval, 0.67-0.82)] for our internal data and moderate discrimination [63% (95% confidence interval, 0.57-0.69)] for the external data group, which is an improvement over the Spitz model for white subjects. Existing lung cancer prediction models may not be appropriate for predicting risk for African-Americans because (a) they were developed using white populations, (b) level of risk is different for risk factors that African-American share with whites, and (c) unique group-specific risk factors exist for African-Americans. This study developed and validated a risk prediction model for lung cancer that is specific to African-Americans and thus more precise in predicting their risks. These findings highlight the importance of conducting further ethnic-specific analyses of disease risk.

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