bluuebunny/crossref_metadata_2025_split huggingface dataset:
Texture Features from Mammographic Images and Risk of Breast Cancer
Authors: Manduca Armando , Carston Michael J. , Heine John J. , Scott Christopher G. , Pankratz V. Shane , Brandt Kathy R. , Sellers Thomas A. , Vachon Celine M. , Cerhan James R. 
Published: March 2009

AbstractMammographic percent density (PD) is a strong risk factor for breast cancer, but there has been relatively little systematic evaluation of other features in mammographic images that might additionally predict breast cancer risk. We evaluated the association of a large number of image texture features with risk of breast cancer using a clinic-based case-control study of digitized film mammograms, all with screening mammograms before breast cancer diagnosis. The sample was split into training (123 cases and 258 controls) and validation (123 cases and 264 controls) data sets. Age-adjusted and body mass index (BMI)–adjusted odds ratios (OR) per SD change in the feature, 95% confidence intervals, and the area under the receiver operator characteristic curve (AUC) were obtained using logistic regression. A bootstrap approach was used to identify the strongest features in the training data set, and results for features that validated in the second half of the sample were reported using the full data set. The mean age at mammography was 64.0 ± 10.2 years, and the mean time from mammography to breast cancer was 3.7 ± 1.0 (range, 2.0-5.9 years). PD was associated with breast cancer risk (OR, 1.49; 95% confidence interval, 1.25-1.78). The strongest features that validated from each of several classes (Markovian, run length, Laws, wavelet, and Fourier) showed similar ORs as PD and predicted breast cancer at a similar magnitude (AUC = 0.58-0.60) as PD (AUC = 0.58). All of these features were automatically calculated (unlike PD) and measure texture at a coarse scale. These features were moderately correlated with PD (r = 0.39-0.76), and after adjustment for PD, each of the features attenuated only slightly and retained statistical significance. However, simultaneous inclusion of these features in a model with PD did not significantly improve the ability to predict breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(3):837–45)
The Relationship between Gene-Specific DNA Methylation in Leukocytes and Normal Colorectal Mucosa in Subjects with and without Colorectal Tumors
Authors: Ally Mina Sarah , Al-Ghnaniem Reyad , Pufulete Maria 
Published: March 2009

AbstractCpG island methylation in the promoter regions of tumor suppressor genes has been shown to occur in normal colonic tissue and can distinguish between subjects with and without colorectal neoplasms. It is unclear whether this relationship exists in other tissues such as blood. We report the relationship between estrogen receptor gene (estrogen receptor α) methylation in leukocyte and normal colonic tissue DNA in subjects with and without colorectal neoplasia. DNA was extracted from frozen stored whole blood samples of 27 subjects with cancer, 30 with adenoma, 16 with hyperplastic polyps, and 57 disease-free subjects. DNA methylation in seven CpG sites close to the transcription start of estrogen receptor α was quantitated using pyrosequencing and expressed as a methylation index (average methylation across all CpG sites analyzed). Estrogen receptor α methylation in leukocyte DNA was compared with estrogen receptor α methylation in normal colonic mucosa DNA that had been previously determined in the same subjects. Estrogen receptor α was partially methylated (median, 4.3%; range, 0.0-12.6%) in leukocyte DNA in all subjects, with no significant difference between disease groups (P &gt; 0.05). Estrogen receptor α methylation in leukocytes was 60% lower than estrogen receptor α methylation in normal colonic tissue (P &lt; 0.001). Estrogen receptor α methylation in colonic tissue (P &lt; 0.001) and smoking (P = 0.016) were determinants of estrogen receptor α methylation in leukocytes, independent of age, body mass index, gender, and disease status. In conclusion, there was a positive relationship between estrogen receptor α methylation in leukocytes and colonic tissue in subjects with and without colorectal tumors. However, unlike in colonic tissue, estrogen receptor α methylation in leukocytes was unable to distinguish between disease groups. (Cancer Epidemiol Biomarkers Prev 2009;18(3):922–8)
Nipple Aspirate Fluid Collection, Related Factors and Relationship between Carcinoembryonic Antigen in Nipple Aspirate Fluid and Breast Diseases in Women in Harbin, PRC
Authors: Zhao Ya-shuang , Pang Da , Wang Fan , Xue Ying-wei , Gao Dan-ning , Li Hui , Li Kang , Wang Bin-you , Wang Da , Li Hong-yuan 
Published: March 2009

Abstract
This study aimed to examine the factors related to the ability to obtain nipple aspirate fluids in Chinese women and to evaluate the diagnostic value of carcinoembryonic antigen (CEA) in nipple aspiration fluids. Cross-sectional and case-control studies were used to examine the factors associated with the ability to obtain nipple aspiration fluids. A matched case-control study was used to explore the association of CEA level in nipple aspiration fluids with breast disease. CEA level was log10-transformed to normalize the distribution. Univariate and multivariate logistic regression were adopted to analyze the variables in relation to obtaining fluid and the association of its CEA levels and breast diseases. Receiver operating characteristic curve was used to evaluate the value of CEA levels for the detection of breast disease. The nipple aspiration fluid collection rate was 34.24% (201 of 587). Multivariate logistic regression analysis results showed the following to be significantly associated with a greater ability to obtain nipple aspiration fluids: earlier age at menarche [odds ratio (OR), 2.61; 95% confidence interval (95% CI), 1.15-5.91], lactating &gt;12 months (OR, 2.28; 95% CI, 1.44-3.60), wet-type ear wax (OR, 3.80; 95% CI, 2.39-6.02), and fatty diet (OR, 1.56; 95% CI, 1.02-2.39). CEA levels in nipple aspiration fluids of cancerous breasts were significantly higher than those from breasts with benign disease and healthy controls (ORadj, 5.39; P &lt; 0.01). However, the sensitivity of CEAs was 35.42% and the specificity was 85.42% whereas the CEA cutoff value was 307.61 ng/mL. The area under the receiver operating characteristic curve was 0.65. The nipple aspiration fluid collection rate in Chinese native women is lower compared to non-Asian-descendant women. CEA level does not seem to be a useful diagnostic tool for early cancer detection; it can only be used in conjugation with other methods. (Cancer Epidemiol Biomarkers Prev 2009;18(3):732–8)
Suboptimal DNA Repair Capacity Predisposes Coke-Oven Workers To Accumulate More Chromosomal Damages in Peripheral Lymphocytes
Authors: Cheng Juan , Leng Shuguang , Li Haishan , Huang Chuanfeng , Niu Yong , Zhang Linyuan , Liang Xuemiao , Lin Han , Zheng Yuxin 
Published: March 2009

AbstractDNA repair is an essential mechanism for cells to maintain their genomic integrity under endogenous or exogenous assault. Reduced DNA repair capacity (DRC) is associated with increased risk for several environmentally related cancers. The micronucleus in peripheral lymphocytes has been validated as a biomarker of chromosomal damage, increasing cancer risk in human populations. We hypothesized that suboptimal DRC is associated with the increase in chromosomal damage among 94 coke-oven workers and 64 noncoke-oven controls. DRC was evaluated in isolated lymphocytes by comet assay. Chromosomal damage in peripheral lymphocytes was detected by cytokinesis-block micronucleus assay. Four common coding single nucleotide polymorphisms in the XRCC1 gene were genotyped. Coke-oven workers have significantly increased urinary 1-hydroxypyrene (9.0; 6.8-11.7 μg/L versus 1.5, 1.3-1.7 μg/L; P &lt; 0.01) and micronucleus frequency (7.4‰ ± 4.3‰ versus 3.0‰ ± 3.0‰; P &lt; 0.01), and decreased DRC (55.9% ± 16.4% versus 63.6% ± 18.5%; P &lt; 0.01) compared with controls. Significant correlations between DRC and micronucleus frequency were found in coke-oven workers (r = −0.32; P &lt; 0.01; n = 94) and all study subjects (r = −0.32; P &lt; 0.001; n = 158) but not in controls (r = −0.21; P = 0.11; n = 64). Variants of the Arg399Gln polymorphism were associated with a decreased DRC in both coke-oven workers (51.6% ± 16.1% versus 60.6% ± 15.7%; P &lt; 0.01) and controls (59.1% ± 18.5% versus 68.4% ± 17.5%; P = 0.04). The complicated interrelationship of these multiple biomarkers was also identified by path analysis. These findings should facilitate developing a biomarker-based risk assessment model for lung cancer in this occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(3):987–93)
Analysis of Colorectal Adenoma Recurrence Data Subject to Informative Censoring
Authors: Hsu Chiu-Hsieh , Taylor Jeremy M.G. , Long Qi , Alberts David S. 
Published: March 2009

Abstract
The treatment effect of a colorectal polyp prevention trial is often evaluated from the colorectal adenoma recurrence status at the end of the trial. However, early colonoscopy from some participants complicates estimation of the final study end recurrence rate. The early colonoscopy could be informative of status of recurrence and induce informative differential follow-up into the data. In this article, we use midpoint imputation to handle interval-censored observations. We then apply a weighted Kaplan-Meier method to the imputed data to adjust for potential informative differential follow-up, while estimating the recurrence rate at the end of the trial. In addition, we modify the weighted Kaplan-Meier method to handle a situation with multiple prognostic covariates by deriving a risk score of recurrence from a working logistic regression model and then use the risk score to define risk groups to perform weighted Kaplan-Meier estimation. We argue that midpoint imputation will produce an unbiased estimate of recurrence rate at the end of the trial under an assumption that censoring only depends on the status of early colonoscopy. The method described here is illustrated with an example from a colon polyp prevention study. (Cancer Epidemiol Biomarkers Prev 2009;18(3):712–7)
Is it Time to Test Metformin in Breast Cancer Clinical Trials?
Authors: Cazzaniga Massimiliano , Bonanni Bernardo , Guerrieri-Gonzaga Aliana , Decensi Andrea 
Published: March 2009

Abstract
Several studies have identified an increased risk of cancer in type 2 diabetic patients and this is in accordance with the hypothesis that increased insulin levels might promote cancer. Thus, there is a great interest in exploring the possibility that antidiabetic therapies lowering insulin levels could decrease cancer incidence or cancer-related mortality. Recent observational studies have shown that metformin, an oral safe and well-tolerated insulin-sensitizer antidiabetic drug, has been associated with reduced cancer risk. Recently, several preclinical studies have evaluated the effect of metformin in vivo on nude mice and showed a significant reduction of both breast epithelial cell proliferation and protein synthesis. Further investigations in the clinical setting are well-supported by the promising results obtained thus far. At the European Institute of Oncology, the Division of Cancer Prevention and Genetics is planning to conduct a clinical trial to evaluate the activity of metformin on tumor cell proliferation in breast cancer patients undergoing surgery. It will be a presurgical randomized, double blind, placebo-controlled phase II biomarker trial: 100 histologically confirmed breast cancer patients will be randomly assigned to metformin (850 mg twice/daily) or placebo for 28 + 7 days till surgery to assess drug activity on tumor proliferation, as measured by Ki-67. The confirmation of the efficacy of metformin on cancer cell proliferation may lead the way to larger chemoprevention clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(3):701–5)
The Association of Tumor Microsatellite Instability Phenotype with Family History of Colorectal Cancer
Authors: Bapat Bharati , Lindor Noralane M. , Baron John , Siegmund Kim , Li Lin , Zheng Yingye , Haile Robert , Gallinger Steve , Jass Jeremy R. , Young Joanne P. , Cotterchio Michelle , Jenkins Mark , Grove John , Casey Graham , Thibodeau Stephen N. , Bishop D. Timothy , Hopper John L. , Ahnen Dennis , Newcomb Polly A. , Le Marchand Loic , Potter John D. , Seminara Daniela ,   and the Colon Cancer Family Registry
Published: March 2009

Abstract
Family history is a strong predictor of colorectal cancer risk; however, a diagnosis of colorectal cancer among first-degree relatives has not been systematically investigated as a function of the colorectal cancer molecular subtypes related to tumor microsatellite instability (MSI) status. We investigated whether the observable familial colorectal cancer risks differed according to tumor MSI subtypes, stratified as MSI-High (&gt;30% instability), MSI-Low (&lt;30% instability), and MSS (no instability). Data from 3,143 population-based colorectal cancer cases from five institutions were assessed for family history according to the Amsterdam criteria and the Bethesda guidelines, age at diagnosis, sex, tumor location, and MSI status. The distribution of patient characteristics by MSI status was compared using polytomous logistic regression. Overall, 2.8% colorectal cancer cases met the Amsterdam criteria and 37% met the Bethesda guidelines. There were 14% MSI-High, 13% MSI-Low, and 73% MSS colorectal cancers. MSI-High (P &lt; 0.0001) and MSI-Low tumors (P = 0.01) were more proximally located than MSS tumors. MSI-High tumors were more common among females (P &lt; 0.001). The highest proportion of MSI-High tumors occurred in cases &lt;40 years of age whereas the age-dependent distribution of MSI-Low tumors was unchanged. MSI-High tumors showed a statistically significant association with increasing numbers of first-degree relatives with colorectal cancer (P = 0.002); this association disappeared, however, when MSI-High cases meeting Amsterdam criteria were removed from the analysis. MSI-Low tumors did not show a similar association with family history of colorectal cancer. Familial risk associated with MSI-High tumors is primarily driven by the Amsterdam-criteria patients. MSI-Low tumors may represent a distinct subtype of colorectal cancer with respect to certain epidemiologic variables studied here. (Cancer Epidemiol Biomarkers Prev 2009;18(3):967–75)
Cost-Effectiveness Analysis of Mammography and Clinical Breast Examination Strategies: A Comparison with Current Guidelines
Authors: Ahern Charlotte Hsieh , Shen Yu 
Published: March 2009

Abstract
Purpose: Breast cancer screening by mammography and clinical breast exam are commonly used for early tumor detection. Previous cost-effectiveness studies considered mammography alone or did not account for all relevant costs. In this study, we assessed the cost-effectiveness of screening schedules recommended by three major cancer organizations and compared them with alternative strategies. We considered costs of screening examinations, subsequent work-up, biopsy, and treatment interventions after diagnosis.
Methods: We used a microsimulation model to generate women's life histories, and assessed screening and treatment effects on survival. Using statistical models, we accounted for age-specific incidence, preclinical disease duration, and age-specific sensitivity and specificity for each screening modality. The outcomes of interest were quality-adjusted life years (QALY) saved and total costs with a 3% annual discount rate. Incremental cost-effectiveness ratios were used to compare strategies. Sensitivity analyses were done by varying some of the assumptions.
Results: Compared with guidelines from the National Cancer Institute and the U.S. Preventive Services Task Force, alternative strategies were more efficient. Mammography and clinical breast exam in alternating years from ages 40 to 79 years was a cost-effective alternative compared with the guidelines, costing $35,500 per QALY saved compared with no screening. The American Cancer Society guideline was the most effective and the most expensive, costing over $680,000 for an added QALY compared with the above alternative.
Conclusion: Screening strategies with lower costs and benefits comparable with those currently recommended should be considered for implementation in practice and for future guidelines. (Cancer Epidemiol Biomarkers Prev 2009;18(3):718–25)
Predisposing Factors Associated with Compliance to Biennial Breast Screening among Centers with and without Nurses
Authors: Edwards Sarah A. , Chiarelli Anna M. , Stewart Lindsay , Majpruz Vicky , Ritvo Paul , Mai Verna 
Published: March 2009

AbstractBackground: Previous research suggests that predisposing factors such as previous screening experience, participation in preventive health behaviors, and knowledge/beliefs about breast cancer and screening influence a woman's decision to make a timely return for a second screen.Methods: A stratified random sample of compliers and noncompliers to biennial screening were selected from a cohort of 51,242 women ages 50 to 65 years who had their initial screen at the Ontario Breast Screening Program. In total, 1,901 women were telephone-interviewed. The associations between predisposing factors and compliance were estimated separately for centers with and without nurses using logistic regression analyses adjusted for demographics and smoking status.Results: Women screened at nurse centers were less likely to comply if they thought women should stop having mammograms before age 70 years [odds ratio (OR), 0.39; 95% confidence interval (95% CI), 0.19-0.79], did not consider mammograms very likely to find cancer (OR, 0.73; 95% CI, 0.56-0.95), felt their likeliness of getting breast cancer was below average (OR, 0.69; 95% CI, 0.54-0.89), or believed a high-fat diet was not an important risk factor for breast cancer (OR, 0.59; 95% CI, 0.36-0.97). Women attending nurse centers were significantly more likely to comply if they sometimes had thoughts or worries about developing breast cancer (OR, 1.40; 95% CI, 1.10-1.80).Conclusions: Nurses at screening centers may reinforce a woman's knowledge or beliefs about breast cancer or screening and as a result increase their compliance to biennial breast screening. (Cancer Epidemiol Biomarkers Prev 2009;18(3):739–47)
Serum Prostate-Specific Antigen Hemodilution Among Obese Men Undergoing Screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Grubb Robert L. , Black Amanda , Izmirlian Grant , Hickey Thomas P. , Pinsky Paul F. , Mabie Jerome E. , Riley Thomas L. , Ragard Lawrence R. , Prorok Philip C. , Berg Christine D. , Crawford E. David , Church Timothy R. , Andriole Gerald L. ,   for the PLCO Project Team
Published: March 2009

Abstract
Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI.
Results: PSA concentration significantly decreased with increasing BMI (P &lt; 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, &gt;35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories (P = 0.10).
Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men. (Cancer Epidemiol Biomarkers Prev 2009;18(3):748–51)
Public service motivation and organizational performance in Swiss federal government
Authors: Ritz Adrian 
Published: March 2009

During the last 20 years public sector reforms focused on the increase of organizational performance mainly by implementing managerial tools and methods. The one-sided, output-oriented reforms meet with criticism. In our study we focus on the links between employee attitudes, managerial measures, institutional factors and organizational performance. Therefore, three attitudinal constructs, public service motivation, organizational commitment and job satisfaction, are analysed. The study empirically tests the effects of these dimensions on perceived performance in the federal administration of Switzerland. The analysed data of 13,532 federal employees give insight into the importance of employee commitment to the public interest and the need for goal-oriented management techniques. The results are discussed in light of previous studies. Points for practitioners Public administration research raises more and more criticism against New Public Management reforms. This study, however, shows that there is an important link between managerial techniques and the individual perception of organizational performance in administrative practice. There are a range of private management tools immigrating into the public sector. But for the tools to be effective, practitioners need to integrate them with consideration of the specific requirements of the employee's commitment to the public interest.