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Cancer Risk Assessment (cancer + risk_assessment)
Selected AbstractsBacterial and mammalian-cell genotoxicity of mixtures of chlorohydroxyfuranones, by-products of water chlorinationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2004Jorma Mäki-Paakkanen Abstract The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the genotoxicity of the individual compounds. Genotoxicity was evaluated in the Salmonella reversion assay (Ames test), the in vitro Chinese hamster ovary (CHO) cell Hprt mutation assay, and in the CHO chromosome aberration test. When tested individually, the concentrations of the chemicals that were chosen for the mixtures induced no or only a modest increase in the genotoxic effects, and caused little or no cytotoxicity. In the Ames test, the genotoxic responses caused by the mixtures of CHFs did not follow simple additivity. Synergism was observed with strains TA97 and TA98, and antagonism with strain TA100. In the CHO/Hprt mutation assay, the mutagenic response of the mixtures was inconsistent, with near additivity seen with a mixture of CHFs that resulted in 12% cell survival. In contrast, the four CHFs together consistently caused more structural chromosome damage (mainly chromatid-type breaks and exchanges) compared to the sum of net effects of the four CHFs tested alone. Also, a potentiating effect was consistently seen for the cytotoxicity of the CHF mixtures both in the CHO/Hprt mutation assay and the chromosome aberration test. The present results indicate that the genotoxic effects of CHF mixtures can be greater than additive. Such effects may be worth considering in the cancer risk assessment of chlorinated drinking water. Environ. Mol. Mutagen. 43:217,225, 2004. © 2004 Wiley-Liss, Inc. [source] TK/TD dose,response modeling of toxicityENVIRONMETRICS, Issue 5 2007Munni Begum Abstract In environmental cancer risk assessment of a toxic chemical, the main focus is in understanding induced target organ toxicity that may in turn lead to carcinogenicity. Mathematical models based on systems of ordinary differential equations with biologically relevant parameters are tenable methods for describing the disposition of chemicals in target organs. In evaluation of a toxic chemical, dose,response assessment often addresses only toxicodynamics (TD) of the chemical, while its toxicokinetics (TK) do not enter into consideration. The primary objective of this research is to integrate both TK and TD in evaluation of toxic chemicals while performing dose,response assessment. Population models, with hierarchical setup and nonlinear predictors, for TK concentration and TD effect measures are considered. A one-compartment model with biologically relevant parameters, such as organ volume, uptake rate and excretion rate, or clearance, is used to derive the TK predictor while a two parameter Emax model is used as a predictor for TD measures. Inference of the model parameters with nonnegative and assay's Limit of Detection (LOD) constraints was carried out by Bayesian approaches using Markov Chain Monte Carlo (MCMC) techniques. Copyright © 2006 John Wiley & Sons, Ltd. [source] Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokersINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Sabine Zöchbauer-Müller Abstract An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor ,-2 (RAR,- 2), CDH13 (H-cadherin), p16INK4a (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RAR,- 2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens. © 2003 Wiley-Liss, Inc. [source] Pre- and posttest evaluation of a breast cancer risk assessment program for nurse practitionersJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2010FAANP (Associate Professor), FNP-C, Quannetta T. Edwards BSN, WHCNP-C Abstract Purpose: Numerous studies have shown that healthcare providers, including nurse practitioners (NPs) fail to provide breast cancer risk assessment (BrCRA) in primary care settings. A potential barrier to the use of BrCRA is insufficient knowledge or training of risk assessment. The purpose of this study was to analyze the outcome of a BrCRA program developed to enhance NPs' knowledge of risk assessment and use of empiric risk assessment models. Data sources: Thirty-five NPs participated in a before-after (pretest,posttest design) study evaluating the effectiveness of a BrCRA education program conducted at a national NP conference. Demographics, pre/post knowledge, and course satisfaction measures were all examined as a part of this pilot study. Conclusion: Continuing education through the implementation of a BrCRA program significantly increased NPs knowledge in assessing breast cancer risk and the use of empiric risk assessment models. Implications for practice: Many healthcare providers, including NPs, are inadequately prepared to assess a woman's risk for breast cancer. Understanding breast cancer risk assessment is essential if NPs are to provide appropriate counseling, management, and referral strategies needed to reduce a woman's risk for developing the disease. Continuing education provides one means to enhance NP's knowledge of BrCRA. [source] Using Family History to Assess Women's Cancer Risk in a Parish Nurse SettingNURSING & HEALTH SCIENCES, Issue 2 2006Carol Cherry This health promotion project fulfillled required field study in a graduate public health nursing program. Family history, an important risk factor for many chronic diseases including cancer, is gaining importance as a public health tool. The author used cancer risk assessment expertise to assess women's cancer risk based on family history in two parish settings. Women completed cancer family history using the U.S. Surgeon General's Family Health Portrait. They received pedigree, tailored risk communication and educational materials for cancer prevention/detection. Of 23 women, the majority reported intention to: (i) change behavior to reduce risk; (ii) change screening practice; and (iii) share family history with healthcare providers. One woman at high risk sought formal genetic counseling. Risk information was based on family history only, although multiple factors affect risk. Women's intention to change behavior may not lead to actual change. Population was homogeneous and well educated so results may not be generalizable to other populations. Even though most parish nurses would not have expertise in cancer risk assessment, they can advocate use of the Family Health Portrait. Women respond positively to personalized risk feedback presented in the context of their faith communities. The project facilitated genomic understanding within a public health setting. [source] Developments in asbestos cancer risk assessment,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 11 2009Michael A. Silverstein MD Abstract Background Efforts have been made for 25 years to develop asbestos risk assessments that provide valid information about workplace and community cancer risks. Mathematical models have been applied to a group of workplace epidemiology studies to describe the relationships between exposure and risk. EPA's most recent proposed method was presented at a public meeting in July 2008. Methods Risk assessments prepared by USEPA, OSHA, and NIOSH since 1972 were reviewed, along with related literature. Results and Conclusions None of the efforts to use statistical models to characterize relative cancer potencies for asbestos fiber types and sizes have been able to overcome limitations of the exposure data. Resulting uncertainties have been so great that these estimates should not be used to drive occupational and environmental health policy. The EPA has now rejected and discontinued work on its proposed methods for estimating potency factors. Future efforts will require new methods and more precise and reliable exposure assessments. However, while there may be genuine need for such work, a more pressing priority with regard to the six regulated forms of asbestos and other asbestiform fibers is to ban their production and use. Am. J. Ind. Med. 52:850,858, 2009. © 2009 Wiley-Liss, Inc. [source] Biomarker Assays in Nipple Aspirate FluidTHE BREAST JOURNAL, Issue 6 2001Pamela Klein MD The noninvasive technique of nipple aspiration as a potential source of biomarkers of breast cancer risk was evaluated. The feasibility of performing mutagenesis assays, amplifying DNA, and performing protein electrophoresis on nipple aspirate fluid was explored. A tool was developed to measure the level of discomfort, if any, from this procedure. Twenty-five healthy women (20 premenopausal and 5 postmenopausal) were enrolled. Fluid was obtained using a modified breast pump. Premenopausal women were scheduled for four to six weekly aspirations, and postmenopausal women were scheduled for one to two weekly aspirations. Mutagenesis assays were performed using the Salmonella (Ames) assay. DNA amplification of several microsatellite regions was carried out using polymerase chain reaction. Protein was quantified, and two-dimensional protein electrophoresis was performed. Overall, fluid was obtained from 80% of the women, and the level of discomfort was minimal. Acid hydrolysis of one sample resulted in mutagenicity; all six nonhydrolyzed samples were not mutagenic. The ability to amplify DNA ranged from 34% to 96%, depending on length of the microsatellite region examined. The average protein concentration was 71 ,g/mL. Two-dimensional protein electrophoresis was successfully performed on samples from two subjects. Nipple aspiration is a simple technique and is easily learned and well tolerated, which yields a reagent useful for a variety of investigations. This technique may facilitate the identification and application of biomarkers for future breast cancer risk assessment and chemopreventive protocols. [source] Genetic variants in cell cycle control pathway confer susceptibility to bladder cancerCANCER, Issue 11 2008Yuanqing Ye PhD Abstract BACKGROUND Cell cycle checkpoint regulation is crucial for the prevention of carcinogenesis in mammalian cells. METHODS To test the hypothesis that common sequence variants in the cell cycle control pathway may affect bladder cancer susceptibility, the effects of a panel of 10 potential functional single nucleotide polymorphisms (SNPs) from 7 cell cycle control genes, P53, P21, P27, CDK4, CDK6, CCND1, and STK15, were evaluated on bladder cancer risk in a case-control study of 696 bladder cancer cases and 629 healthy controls. RESULTS Overall, on individual SNP analysis only individuals with the p53 intron 3 16-bp duplication polymorphism variant allele had a significantly reduced bladder cancer risk (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.56,0.96). This effect was more evident in former smokers and younger subjects. We then applied the Classification and Regression Tree (CART) statistical approach to explore the high-order gene-gene and gene-smoking interactions. In the CART analysis, smoking status was identified as the most influential factor for bladder cancer susceptibility. The final decision tree by CART contained 6 terminal nodes. Compared with the second-lowest risk group the ORs for terminal nodes 1 and 3 to 6 ranged from 0.46 to 6.30. CONCLUSIONS These results suggest that cell cycle genetic polymorphisms may affect bladder cancer predisposition through modulation of host genome stability and confirm the importance of studying gene-gene and gene-environment interactions in bladder cancer risk assessment. Cancer 2008. © 2008 American Cancer Society. [source] | ||||||||||