bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Methylacyl-CoA Racemase Protein Expression Is Associated with the Degree of Differentiation in Breast Cancer Using Quantitative Image Analysis
Authors: Witkiewicz Agnieszka K. , Varambally Sooryanarayana , Shen Ronglai , Mehra Rohit , Sabel Michael S. , Ghosh Debashis , Chinnaiyan Arul M. , Rubin Mark A. , Kleer Celina G. 
Published: September 2005

Abstractα-Methylacyl-CoA racemase (AMACR) is an enzyme involved in the metabolism of fatty acids and is an important tissue biomarker in the prostate to distinguish normal glands from prostate cancer. Here, for the first time, we evaluated the expression of AMACR protein in normal breast, ductal carcinoma in situ, and invasive carcinomas. By immunofluorescence and immunohistochemistry, AMACR was seen in cytoplasmic granules consistent with a mitochondrial and peroxisomal localization. AMACR expression was determined by immunohistochemistry on 160 invasive carcinomas with long follow-up, using a high-density tissue microarray, and evaluated by two methods: standard pathology review and quantitative image analysis. AMACR was overexpressed in 42 of 160 (26%) invasive carcinomas, and it was associated with a decrease in tumor differentiation, a feature of aggressive breast cancer. Quantitative analysis allowed for better discrimination and more accurate evaluation of low-intensity staining. In conclusion, AMACR protein is expressed in normal breast and its expression seems to increase in invasive carcinomas. We observed stronger AMACR protein expression in high-grade carcinomas when compared with low-grade ones. Quantitative image analysis is a novel way to accurately and reproducibly evaluate immunohistochemistry in breast tissue samples using high-density tissue microarrays.
Project PREVENT: A Randomized Trial to Reduce Multiple Behavioral Risk Factors for Colon Cancer
Authors: Emmons Karen M. , McBride Colleen M. , Puleo Elaine , Pollak Kathryn I. , Clipp Elizabeth , Kuntz Karen , Marcus Bess H. , Napolitano Melissa , Onken Jane , Farraye Frank , Fletcher Robert 
Published: September 2005

Abstract
Background: This report examines the outcome data for Project PREVENT, a two-site randomized control trial designed to reduce behavioral risk factors for colorectal cancer among individuals who have been diagnosed with adenomatous colon polyps.
Methods: The study sample included 1,247 patients with recent diagnosis of adenomatous colorectal polyps. Within 4 weeks following the polypectomy, participants completed a baseline survey by telephone, and were randomized to either Usual Care (UC) or the PREVENT intervention, which was designed to target multiple risk factors. The intervention consisted of a telephone-delivered intervention plus tailored materials, and focused on the six primary behavioral risk factors for colorectal cancer, including red meat consumption, fruit and vegetable intake, multivitamin intake, alcohol, smoking, and physical inactivity.
Results: Participation in the PREVENT intervention was associated with a significantly greater reduction in prevalence of multiple risk factors for colorectal cancer compared with UC. Only about one third of UC participants dropped any risk factors during the study period, compared with almost half of the PREVENT participants. PREVENT participants were also significantly more likely to change more than one behavior than UC participants.
Conclusions: The PREVENT intervention was effective in helping patients change multiple risk factors. These results provide further support that more comprehensive interventions that move beyond emphasis on a single risk factor are acceptable to patient populations, can result in improvements, and are cost effective.
Tumor Antigen Markers for the Detection of Solid Cancers in Inflammatory Myopathies
Authors: Amoura Zahir , Duhaut Pierre , Huong Du Le Thi , Wechsler Bertrand , Costedoat-Chalumeau Nathalie , Francès Camille , Cacoub Patrice , Papo Thomas , Cormont Sylvie , Touitou Yvan , Grenier Philippe , Valeyre Dominique , Piette Jean-Charles 
Published: September 2005

Abstract
Dermatomyositis and polymyositis patients have an increased risk of developing cancers. We have assessed the diagnostic values of serum tumor markers for the detection of solid cancer in dermatomyositis/polymyositis patients. Serum carcinoembryonic antigen, CA15-3, CA19-9, and CA125 were assayed by immunoradiometric methods in 102 dermatomyositis/polymyositis patients. All the patients had complete physical examination, chest X-ray, echocardiogram, gastrointestinal tract endoscopic explorations, thoracoabdomino-pelvic computed tomography scan, and all women had gynecologic examination and mammogram. Exclusion criteria for study were childhood dermatomyositis, inclusion body myositis, myositis associated with a connective tissue disease, prior history of cancer, and the presence of benign conditions known to elevate serum tumor markers. After a median follow-up of 59 months, 10 (9.8%) patients had a solid cancer. Initial elevation of CA125 was associated with an increased risk of developing solid cancer [P = 0.0001 by Fisher's exact test; odds ratio (OR), 29.7; 95% confidence interval (95% CI), 8.2-106.6]. For CA19-9, there was a trend towards a significant association (P = 00.7; OR, 4.5; 95% CI, 1-18.7, respectively). Diagnostic values of elevated CA125 and CA19-9 at screening increased when the study analysis was restricted to patients who developed a cancer within 1 year (P &lt; 0.0001 and P = 0.018, respectively) or to patients without interstitial lung disease (P = 0.00001; OR, 133; 95% CI, 6.5-2733 and P = 0.027; OR, 9; 95% CI, 1.5-53, respectively). Individual comparisons of the baseline and the second CA125 value showed that three of the eight patients with cancers versus 3 of the 76 patients without, displayed an increase of their CA125 level (P = 0.01 by Fisher's exact test). We conclude that CA125 and CA19-9 assessment could be useful markers of the risk of developing tumors for patients with dermatomyositis and polymyositis and should therefore be included in the search for cancer in dermatomyositis/polymyositis patients, especially for patients without interstitial lung disease.
Risk Factors for Melanoma by Body Site
Authors: Cho Eunyoung , Rosner Bernard A. , Colditz Graham A. 
Published: September 2005

Abstract
It has been hypothesized that cutaneous melanoma at different anatomic sites develops through divergent pathways. We examined this hypothesis prospectively. We followed 152,949 women and 25,204 men free of cancer at baseline for up to 14 years in three large prospective studies. We examined risk factors for melanoma by anatomic location (head or neck, trunk, upper extremity, and lower extremity). Polytomous logistic regression was used to test the difference among risk factors by location of melanoma. A total of 511 incident cases of invasive melanoma (49 head or neck, 188 trunk, 98 upper extremity, and 176 lower extremity) were included in the analysis. Compared with females, males had a higher risk of developing melanoma on the head or neck and trunk. History of severe and painful sunburn was most strongly related to melanoma of upper extremity; individuals with &gt;10 burns had a 6.86-fold (95% confidence interval, 2.62-18.00) higher risk of melanoma of upper extremity compared with those with no burns (P for trend &lt; 0.0001; P for difference by body site = 0.04). Number of moles was most strongly related to melanoma of the trunk; the multivariate relative risk for having &gt;10 moles was 4.67 (95% confidence interval, 3.07-7.11) compared with having no moles (P for trend &lt; 0.0001; P for difference by body site = 0.04). Age, family history of melanoma, and hair color did not statistically differ by anatomic site of the cancer. These data support divergent etiologic pathways of melanoma development by anatomic sites.
Association of Susceptibility Alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with Prostate Cancer Severity in European American and African American Men
Authors: Rennert Hanna , Zeigler-Johnson Charnita M. , Addya Kathakali , Finley Matthew J. , Walker Amy H. , Spangler Elaine , Leonard Debra G.B. , Wein Alan , Malkowicz S. Bruce , Rebbeck Timothy R. 
Published: September 2005

Abstract
Reported associations of ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer have been inconsistent and understudied in African Americans. We evaluated the role of 16 sequence variants in these genes with prostate cancer using 888 European American and 131 African American cases, and 473 European American and 163 African American, controls. We observed significant differences in ELAC2, RNASEL, and MSR1 allele frequencies by race. However, we did not observe significant associations between prostate cancer and any variants examined for both races combined. Associations were observed when stratified by race, family history, or disease severity. European American men homozygous for MSR1 IVS7delTTA had an elevated risk for localized stage [odds ratio, (OR), 3.5; 95% confidence interval (95% CI), 1.4-6.9], low-grade (OR, 3.2; 95% CI, 1.4-7.3) disease overall, and with low-grade (OR, 2.9; 95% CI, 1.2-7.2) or late-stage disease (OR, 5.2; 95% CI, 1.1-25.7) in family history–negative African Americans. MSR1 Arg293X was associated with family history–negative high-grade disease (OR, 4.0; 95% CI, 1.1-14.1) in European Americans. RNASEL Arg462Gln was associated with low-grade (OR, 1.5; 95% CI, 1.04-2.2) and early-stage (OR, 1.5; 95% CI, 1.02-2.1) disease in family history–negative European Americans. In family history–positive individuals, Arg462Gln was inversely associated with low-grade (OR, 0.43; 95% CI, 0.21-0.88) and low-stage (OR, 0.46; 95% CI, 0.22-0.95) disease. In African Americans, Arg462Gln was associated with positive family history high-stage disease (OR, 14.8; 95% CI, 1.6-135.7). Meta-analyses revealed significant associations of prostate cancer with MSR1 IVS7delTTA, −14,742 A&gt;G, and Arg293X in European Americans; Asp174Tyr in African Americans; RNASEL Arg462Gln in European American's overall and in family history–negative disease; and Glu265X in family history–positive European Americans. Therefore, MSR1 and RNASEL may play a role in prostate cancer progression and severity.
Catechol-O-Methyl-Transferase Functional Polymorphism and Nicotine Dependence: an Evaluation of Nonreplicated Results
Authors: Redden David T. , Shields Peter G. , Epstein Leonard , Wileyto E. Paul , Zakharkin Stanislav O. , Allison David B. , Lerman Caryn 
Published: September 2005

Abstract
Review articles have focused attention on and cited possible reasons for the nonreplication of genetic association studies. Herein, we illustrate how one might work through these possible reasons to make a judgment about the most plausible reason(s) when faced with two or more studies which yield seemingly inconsistent results. In the first study, 342 treatment-seeking smokers were genotyped for the Val108Met polymorphism in the functional catechol-O-methyl-transferase (COMT) locus. Alleles coding Val at codon 108 are denoted as H and those coding Met are denoted as L. An association between presence of the “H” (high activity) allele and pretreatment level of nicotine dependence level using the Fagerstrom Test for Nicotine Dependence was detected (P = 0.0072), after controlling for baseline body mass index (BMI, kg/m2), depression symptoms, and age. To validate this initial finding, 443 treatment-seeking smokers from an independent smoking cessation clinical trial were genotyped for the COMT polymorphism. Within the second study, no association between presence of the “H” allele and nicotine dependence was detected (P = 0.6418) after controlling for baseline BMI, depression symptoms, and age. We critically reviewed both studies with regard to often cited reasons for nonreplication, including type I error, population stratification, low statistical power, and imprecise measures of phenotype. Although in our opinion the failure to replicate the initial association in the second study is likely either the result of low statistical power to detect a small effect or effect heterogeneity, thorough analyses failed to definitively identify the reason for nonreplication.
The Biology of Tobacco and Nicotine: Bench to Bedside
Authors: Dennis Phillip A. , Van Waes Carter , Gutkind J. Silvio , Kellar Kenneth J. , Vinson Charles , Mukhin Alexey G. , Spitz Margaret R. , Bailey-Wilson Joan E. , Yeh Grace Chao , Anderson Lucy M. , Wiest Jonathan S. 
Published: September 2005

Abstract
Strong epidemiologic evidence links smoking and cancer. An increased understanding of the molecular biology of tobacco-related cancers could advance progress toward improving smoking cessation and patient management. Knowledge gaps between tobacco addiction, tumorigenesis, and cancer brought an interdisciplinary group of investigators together to discuss “The Biology of Nicotine and Tobacco: Bench to Bedside.” Presentations on the signaling pathways and pathogenesis in tobacco-related cancers, mouse models of addiction, imaging and regulation of nicotinic receptors, the genetic basis for tobacco carcinogenesis and development of lung cancer, and molecular mechanisms of carcinogenesis were heard. Importantly, new opportunities to use molecular biology to identify and abrogate tobacco-mediated carcinogenesis and to identify high-risk individuals were recognized.
Changes in Serum Proteomic Patterns by Presurgical α-Tocopherol andl-Selenomethionine Supplementation in Prostate Cancer
Authors: Kim Jeri , Sun Peiyu , Lam Ying-Wai , Troncoso Patricia , Sabichi Anita L. , Babaian Richard J. , Pisters Louis L. , Pettaway Curtis A. , Wood Christopher G. , Lippman Scott M. , McDonnell Timothy J. , Lieberman Ronald , Logothetis Christopher , Ho Shuk-Mei 
Published: September 2005

AbstractBackground: Evidence of the chemopreventive effects of the dietary antioxidants α-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial.Methods: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 × 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software.Results: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups.Conclusion: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer–free status.
Effects of Electron-Beam Irradiation on Whole Genome Amplification
Authors: Bergen Andrew W. , Qi Ying , Haque Kashif A. , Welch Robert A. , Garcia-Closas Montserrat , Chanock Stephen J. , Vaught Jim , Castle Philip E. 
Published: September 2005

Abstract
Electron-beam (E-beam) irradiation, currently being used to sterilize mail addressed to selected ZIP codes in the United States, has significant negative effects on the genomic integrity of DNA extracted from buccal-cell washes. We investigated the yield, composition, and genotyping performance of whole genome amplified DNA (wgaDNA) derived from 24 matched samples of E-beam–irradiated and nonirradiated genomic DNA (gDNA) as a model for the effects of degraded gDNA on the performance of whole genome amplification. gDNA was amplified using the Multiple Displacement Amplification method. Three methods of DNA quantification analysis were used to estimate the yield and composition of wgaDNA, and 65 short tandem repeat and single nucleotide polymorphism genotyping assays were used to evaluate the genotyping performance of irradiated and nonirradiated gDNA and wgaDNA. Compared with wgaDNA derived from nonirradiated gDNA, wgaDNA derived from irradiated gDNA exhibited a significantly reduced yield of wgaDNA and significantly reduced short tandem repeat and single nucleotide polymorphism genotyping completion and concordance rates (P &lt; 0.0001). Increasing the amount of irradiated gDNA input into whole genome amplification improved genotyping performance of wgaDNA but not to the level of wgaDNA derived from nonirradiated gDNA. Multiple Displacement Amplification wgaDNA derived from E-beam–irradiated gDNA is not suitable for genotyping analysis.
Insulin-like Growth Factor Polymorphisms and Colorectal Cancer Risk
Authors: Morimoto Libby M. , Newcomb Polly A. , White Emily , Bigler Jeannette , Potter John D. 
Published: September 2005

AbstractSeveral modifiable lifestyle factors, such as physical activity, obesity, and postmenopausal hormone use, have been associated with colorectal cancer risk. It has been hypothesized that some or all of these factors may mediate their effects through alterations in insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBP). To evaluate the role of IGFs in colorectal cancer, we examined the relationship of two common genetic polymorphisms in IGF-1 (a cytosine-adenosine dinucleotide repeat) and IGFBP-3 (a G → C single nucleotide polymorphism) with colorectal cancer risk, as well as their potential modification by physical activity, body mass index (BMI), and postmenopausal hormone use. Subjects included 782 male and female colorectal cancer cases diagnosed between 1998 and 2002 and reported to the statewide registry in the metropolitan Seattle area, and 503 age- and sex-matched cancer-free population controls. Colorectal cancer was modestly associated with having an IGF-1 genotype other than homozygous for 19 repeats (odds ratio, 1.3; 95% confidence interval, 1.0-1.6) and having the GG IGFBP-3 genotype (odds ratio, 1.3; 95% confidence interval, 1.0-1.8). There was evidence that IGF-1 genotype modified the relationship between BMI and colorectal cancer among women, such that high BMI increased risk of colorectal cancer only among those with the 19/19 genotype (Pinteraction = 0.02). IGFBP-3 genotype was also a significant effect modifier of the relationship between risk factors and colorectal cancer: The positive association between BMI and colorectal cancer was observed only among men (Pinteraction &lt; 0.01) and women (Pinteraction = 0.06) with the GG genotype; the inverse association between postmenopausal hormone use and colorectal cancer was observed only among women with the GG genotype (P = 0.01) and the inverse association between physical activity and colorectal cancer was observed only among men who carried the C allele (P &lt; 0.01). The current study provides some support for a role of IGFs in colorectal cancer etiology, particularly in mediating the relationship of common risk factors (physical activity, BMI, and postmenopausal hormone use).
No Association between Gastroesophageal Reflux and Cancers of the Larynx and Pharynx
Authors: Nilsson Magnus , Chow Wong-Ho , Lindblad Mats , Ye Weimin 
Published: September 2005

Abstract
Purpose: To examine the proposed relation between gastroesophageal reflux disease and cancers of the larynx and pharynx.
Experimental Design: A cohort of 66,965 patients with discharge diagnoses of heartburn, hiatal hernia, or esophagitis was identified in the Swedish Inpatient Register. We observed a total of 376,622 person-years in the cohort. Identification of laryngeal and pharyngeal cancers was achieved through the Swedish Cancer Register. Standardized incidence ratios, the ratio of the observed to the expected number of cancers, derived from the general Swedish population and adjusted for sex, age, and calendar year, was used to estimate the relative risk.
Results: During follow-up, 30 cases of laryngeal and 31 cases of pharyngeal cancer were detected in the cohort. Slightly increased risks of laryngeal [relative risk, 1.6; 95% confidence interval (CI), 1.1-2.2] and pharyngeal carcinomas (relative risk, 1.9; 95% CI, 1.3-2.8) were observed in the total reflux cohort. After stratification to exclude cohort members with a diagnosis of alcoholism, no significant increase in the risk of laryngeal (relative risk, 1.3; 95% CI, 0.8-2.0) or pharyngeal carcinomas (relative risk, 1.0; 95% CI, 0.5-1.6) was found compared with the general population. Furthermore, there were no dose-response patterns of the risk for laryngeal and pharyngeal cancers with years of cohort follow-up, indicators of reflux severity, or specificity of reflux diagnosis.
Conclusion: This study provides no evidence in support of the proposed association between gastroesophageal reflux disease and cancers of the larynx or pharynx.
Serum Testosterone and the Risk of Prostate Cancer: Potential Implications for Testosterone Therapy
Authors: Parsons J. Kellogg , Carter H. Ballentine , Platz Elizabeth A. , Wright E. James , Landis Patricia , Metter E. Jeffrey 
Published: September 2005

AbstractObjective: A potential risk of testosterone replacement therapy is an increase in the incidence of prostate cancer, but it is unclear whether higher levels of serum testosterone are associated with a higher risk of prostate cancer. We prospectively evaluated serum androgen concentrations and prostate cancer risk.Method: Included were 794 members of the Baltimore Longitudinal Study of Aging. We estimated the rate ratio (RR) of prostate cancer by entering serial measures of serum total testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, calculated free testosterone, and free testosterone index (FTI) into a Cox proportional hazards regression model with simple updating.Results: Higher calculated free testosterone was associated with an increased age-adjusted risk of prostate cancer {RRs by quartile: 1.00, 1.52 [95% confidence interval (95% CI), 0.93-2.50], 1.16 (95% CI, 0.61-2.20), 2.59 (95% CI, 1.28-5.25); Ptrend = 0.03}, which persisted after excluding measures in men &lt;45 years of age [RRs by quartile: 1.00, 1.33 (95% CI, 0.78-2.25), 1.26 (95% CI, 0.68-2.33), 1.89 (95% CI, 0.99-3.61); Ptrend = 0.03]. Compared to men with eugonadal FTI (≥0.153), men with hypogonadal FTI had a decreased risk of prostate cancer (RR, 0.51; 95% CI, 0.31-0.82).Conclusion: Higher levels of calculated serum free testosterone are associated with an increased risk of prostate cancer. These findings suggest that men receiving testosterone therapy should be regularly monitored for prostate cancer and underscore the need for prospective trials of testosterone therapy incorporating incidence of prostate cancer as a primary safety end point.