bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Levels of Inflammatory Markers and Cancer Risk in the Health Aging and Body Composition Cohort
Authors: Il'yasova Dora , Colbert Lisa H. , Harris Tamara B. , Newman Anne B. , Bauer Douglas C. , Satterfield Suzanne , Kritchevsky Stephen B. 
Published: March 2006

Abstract
Background: Chronic inflammation is associated with processes that contribute to the onset or progression of cancer. This study examined the relationships between circulating levels of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) and total as well as site-specific cancer incidence.
Methods: Study subjects (n = 2,438) were older adults (ages 70-79 years) participating in the Health Aging and Body Composition study, who did not report a previous cancer diagnosis (except for nonmelanoma skin cancer) at baseline. Incident cancer events (n = 296) were ascertained during an average follow-up of 5.5 years. Inflammatory markers were measured in stored baseline fasting blood samples.
Results: The adjusted hazard ratios (95% confidence intervals) for incident cancer associated with a 1-unit increase on the natural log-scale were 1.13 (0.94-1.37), 1.25 (1.09-1.43), and 1.28 (0.96-1.70) for IL-6, CRP, and TNF-α, respectively. Markers were more strongly associated with cancer death: hazard ratios were 1.63 (1.19-2.23) for IL-6, 1.64 (1.20-2.24) for CRP, and 1.82 (1.14-2.92) for TNF-α. Although precision was low for site-specific analyses, our results suggest that all three markers were associated with lung cancer, that IL-6 and CRP were associated with colorectal cancer, and that CRP was associated with breast cancer. Prostate cancer was not associated with any of these markers.
Conclusions: These findings suggest that (a) the associations between IL-6, CRP, and TNF-α and the risk of cancer may be site specific and (b) increased levels of inflammatory markers are more strongly associated with the risk of cancer death than cancer incidence.
Molecular Profiling of Computed Tomography Screen-Detected Lung Nodules Shows Multiple Malignant Features
Authors: Pajares María J. , Zudaire Isabel , Lozano María D. , Agorreta Jackeline , Bastarrika Gorka , Torre Wenceslao , Remírez Ana , Pio Ruben , Zulueta Javier J. , Montuenga Luis M. 
Published: March 2006

Abstract
Rationale and Purpose: Low-dose spiral computerized axial tomography (spiral CT) is effective for the detection of small early lung cancers. Although published data seem promising, there has been a significant degree of discussion concerning the potential of overdiagnosis in the context of spiral CT–based screening. The objective of the current study was to analyze the phenotypic and genetic alterations in the small pulmonary malignancies resected after detection in the University of Navarra/International Early Lung Cancer Action Project spiral CT screening trial and to determine whether their malignant molecular features are similar to those of resected lung tumors diagnosed conventionally.
Experimental Design: We analyzed 17 biomarkers of lung epithelial malignancy in a series of 11 tumors resected at our institution during the last 4 years (1,004 high-risk individuals screened), using immunohistochemistry and fluorescence in situ hybridization (FISH). A parallel series of 11 gender-, stage-, and histology-matched lung cancers diagnosed by other means except screening was used as control.
Results: The molecular alterations and the frequency of phenotypic or genetic aberrations were very similar when screen-detected and nonscreen-detected lung cancers were compared. Furthermore, most of the alterations found in the screen-detected cancers from this study were concordant with what has been described previously for stage I-II lung cancer.
Conclusions: Small early-stage lung cancers resected after detection in a spiral CT-based screening trial reveal malignant molecular features similar to those found in conventionally diagnosed lung cancers, suggesting that the screen-detected cancers are not overdiagnosed. (Cancer Epidemiol Biomarkers Prev 2006;15(2):373–80)
Discovery of Novel Methylation Biomarkers in Cervical Carcinoma by Global Demethylation and Microarray Analysis
Authors: Sova Pavel , Feng Qinghua , Geiss Gary , Wood Troy , Strauss Robert , Rudolf Vania , Lieber Andre , Kiviat Nancy 
Published: March 2006

Abstract
A genome-wide screening study for identification of hypermethylated genes in invasive cervical cancer (ICC) was carried out to augment our previously discovered panel of three genes found to be useful for detection of ICC and its precursor neoplasia. Putatively hypermethylated and silenced genes were reactivated in four ICC cell lines by treatment with 5-aza-2′-deoxycytidine and trichostatin A and identified on expression microarrays. Thirty-nine of the 235 genes up-regulated in multiple ICC cell lines were further examined to determine the methylation status of associated CpG islands. The diagnostic use of 23 genes that were aberrantly methylated in multiple ICC cell lines were then analyzed in DNA from exfoliated cells obtained from patients with or without ICC. We show, for the first time, that aberrant methylation of six genes (SPARC, TFPI2, RRAD, SFRP1, MT1G, and NMES1) is present in a high proportion of ICC clinical samples but not in normal samples. Of these genes, SPARC and TFPI2 showed the highest frequency of aberrant methylation in ICC specimens (86.4% for either) and together were hypermethylated in all but one ICC cases examined. We conclude that expression profiling of epigenetically reactivated genes followed by methylation analysis in clinical samples is a powerful tool for comprehensive identification of methylation markers. Several novel genes identified in our study may be clinically useful for detection or stratification of ICC and/or of its precursor lesions and provide a basis for better understanding of mechanisms involved in development of ICC. (Cancer Epidemiol Biomarkers Prev 2006;(15)1:114–23)
Explaining the Socioeconomic Variation in Cancer Risk in the Norwegian Women and Cancer Study
Authors: Braaten Tonje , Weiderpass Elisabete , Kumle Merethe , Lund Eiliv 
Published: March 2006

Abstract
Associations between level of education and cancer risk is well supported by scientific evidence, but previous studies could only partly adjust for relevant confounding factors. In this article, we examined how risk of cancer varies with level of education and identified factors that explain this variation using data from a prospective cohort study, including 93,638 Norwegian women who responded to an extensive questionnaire in 1991/1992 or 1996/1997. A total of 3,259 incident primary invasive cancer cases were diagnosed during follow-up, which ended in December 2001. We used Cox proportional hazards model to calculate relative risks (RR) with 95% confidence intervals (95% CI). Besides a similar overall risk of female cancers by level of education, we observed differing risks between educational groups for cancers of the lung, breast, cervix, kidney, and skin melanoma. Women with &gt;16 years of education had an increased risk of breast cancer (RR, 1.46; 95% CI, 1.19-1.79) and a decreased risk of lung cancer (RR, 0.30; 95% CI, 0.13-0.70) and cervical cancer (RR, 0.38; 95% CI, 0.17-0.85) compared with the lowest educated women (7-9 years). The middle educated (13-16 years) had the lowest risk of kidney cancer (RR, 0.24; 95% CI, 0.08-0.71), whereas the risk of skin melanoma was highest among women with 10 to 12 years of education (RR, 1.53; 95% CI, 1.05-2.24) compared with the lowest educated women. After multivariate adjustment for potential confounders related to level of education, the variation in cancer risk according to educational levels declined into nonsignificance for all these sites.
Familial Aggregation and Heterogeneity of Non-Hodgkin Lymphoma in Population-Based Samples
Authors: Goldin Lynn R. , Landgren Ola , McMaster Mary L. , Gridley Gloria , Hemminki Kari , Li Xinjun , Mellemkjaer Lene , Olsen Jørgen H. , Linet Martha S. 
Published: March 2006

AbstractThe importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.
Reduction in Breast Cancer Mortality from Organized Service Screening with Mammography: 1. Further Confirmation with Extended Data
Authors:   The Swedish Organised Service Screening Evaluation Group
Published: March 2006

Abstract
Background: In an earlier publication, our evaluation of data from breast cancer screening programs in seven Swedish counties suggested a 40% reduction in incidence-based breast cancer mortality among women actually screened. In the current study, we expand the previous analysis from seven counties to 13 large areas within nine counties, including six of the original counties and seven additional areas, examine a longer period of follow-up (20-44 years), apply new analytic methods for the evaluation of incidence-based breast cancer mortality, and estimate the number needed to screen to save one life.
Methods: Data from six of the original counties (one being excluded as it does not yet have 10 years of follow-up after the initiation of screening), with increased follow-up, and seven additional large areas, within three counties, representing ∼45% of Swedish women, provide information about age at diagnosis, age at death, and screening history for 542,187 women in the prescreening and 566,423 women in the screening epochs. Regardless of year of diagnosis, there were a total of 6,231 deaths due to breast cancer in the period of study as a whole. Of these, 4,778 were incidence-based deaths in the two epochs, i.e., death among cases diagnosed within either the prescreening or screening period. Data were analyzed using Poisson regression and adjusted, when necessary, for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.
Results: Attendance was uniformly high, averaging 75% in the screening epochs. Recall rates for assessment varied from 4% to 5% at the first round of screening and ∼3% at later rounds. Detection rates averaged five breast cancers per 1,000 women screened in the first round, and four breast cancers per 1,000 women screened in subsequent rounds. There was a significant 45% reduction in incidence-based breast cancer mortality among screened women in the screening epoch relative to incidence-based breast cancer mortality in the prescreening epoch (relative risk, 0.55; 95% confidence intervals, 0.51-0.59). After adjusting for self-selection bias, there still was a significant 43% reduction in incidence-based breast cancer mortality associated with screening (relative risk, 0.57; 95% confidence intervals, 0.53-0.62).
Conclusions: These results indicate a reduction in breast cancer mortality of between 40% and 45% in association with screening, after adjustment for self-selection bias. These results were obtained with modest human costs: the number needed to screen to save one life was estimated as 472. (Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51)
γ-Radiation-Induced Chromosomal Mutagen Sensitivity Is Associated with Breast Cancer Risk in African-American Women: Caffeine Modulates the Outcome of Mutagen Sensitivity Assay
Authors: Natarajan Thanemozhi G. , Ganesan Natarajan , Carter-Nolan Pamela , Tucker Cynthia A. , Shields Peter G. , Adams-Campbell Lucile L. 
Published: March 2006

Abstract
Several different cancer studies have indicated that lymphocyte mutagen sensitivity is a marker of DNA repair deficiency and increased cancer risk. We have used a mutagen sensitivity assay (MSA) measuring γ-radiation-induced chromosomal aberrations in freshly cultured lymphocytes and assessed breast cancer risk in African-American women. Concurrently, we conducted duplicate cultures in the presence of caffeine, which overrides G2 arrest in cultured cells, decreases time to DNA repair, and hence increases the aberration rate. In comparison with the non–caffeine-treated cells, we are conceptually segregating the contribution of DNA repair and time for DNA repair as individual susceptibility phenotypes. Blood samples were obtained from 61 cases and 86 controls at Howard University Hospital. Two sets of whole-blood cultures were established and γ-irradiated (1 Gy) at 67 hours, one of which was treated with caffeine (1 mg/mL). Thereafter, cultures were processed for obtaining metaphase spreads. Fifty metaphases were screened for chromatid breaks. The mean breaks per cell (MBPC) for cases (0.34 ± 0.15) was significantly greater than for controls (0.24 ± 0.12; P &lt; 0.0001). Using the 75th percentile value of controls as a cutoff to define mutagen sensitivity, the sensitive individuals had an odds ratio of 4.5 (95% confidence intervals, 2.2-9.1) for breast cancer compared with individuals that were not sensitive. The adjusted odds ratio was 3.3 (95% confidence intervals, 0.147-73.917), which was statistically significant but was limited by the small number of subjects. The results for caffeine co-culture were not predictive of breast cancer (MBPC: cases, 1.6 ± 0.9 versus controls, 1.5 ± 0.8; P = 0.8663). Comparing the MBPC for caffeine and noncaffeine cultures, there was a correlation in controls (n = 79; Spearman r = 0.4286; P &lt; 0.0001), but not in cases (n = 58; Spearman r = 0.06609; P = 0.6221). This study indicates that the MSA phenotype is a risk factor for breast cancer in African-American women, with a significant effect observable even in small studies. The use of caffeine did not enhance the predictivity of MSA, but the correlation with non-caffeine cultures in controls indicates that the MSA phenotype is due to both DNA repair and G2 arrest capacity. (Cancer Epidemiol Biomarkers Prev 2006;15(3):437–42)
The Interaction of Four Genes in the Inflammation Pathway Significantly Predicts Prostate Cancer Risk
Authors: Xu Jianfeng , Lowey James , Wiklund Fredrik , Sun Jielin , Lindmark Fredrik , Hsu Fang-Chi , Dimitrov Latchezar , Chang Baoli , Turner Aubrey R. , Liu Wennan , Adami Hans-Olov , Suh Edward , Moore Jason H. , Zheng S. Lilly , Isaacs William B. , Trent Jeffrey M. , Grönberg Henrik 
Published: March 2006

Abstract
It is widely hypothesized that the interactions of multiple genes influence individual risk to prostate cancer. However, current efforts at identifying prostate cancer risk genes primarily rely on single-gene approaches. In an attempt to fill this gap, we carried out a study to explore the joint effect of multiple genes in the inflammation pathway on prostate cancer risk. We studied 20 genes in the Toll-like receptor signaling pathway as well as several cytokines. For each of these genes, we selected and genotyped haplotype-tagging single nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in the final analysis. A data mining method, multifactor dimensionality reduction, was used to explore the interaction effects of SNPs on prostate cancer risk. Interaction effects were assessed for all possible n SNP combinations, where n = 2, 3, or 4. For each n SNP combination, the model providing lowest prediction error among 100 cross-validations was chosen. The statistical significance levels of the best models in each n SNP combination were determined using permutation tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5) had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a large number of SNPs in a large sample size is one of the first efforts in exploring the effect of high-order gene-gene interactions on prostate cancer risk, and this is an important contribution to this new and quickly evolving field.
Polymorphisms in the Estrogen Receptor α Gene and Mammographic Density
Authors: van Duijnhoven Fränzel J.B. , Bezemer Irene D. , Peeters Petra H.M. , Roest Mark , Uitterlinden André G. , Grobbee Diederick E. , van Gils Carla H. 
Published: March 2006

AbstractThe presence of the PvuII or the XbaI polymorphism in the estrogen receptor α gene (ESR1, 6q25) has been related to breast cancer risk; however, results are not fully consistent. To further elucidate this relation, we examined these polymorphisms in relation with mammographic density, a measure of dense tissue in the breast, which is strongly associated with breast cancer risk. For this study, 620 participants aged 49 to 68 years were selected from the Prospect-European Prospective Investigation into Cancer and Nutrition cohort. Blood samples, lifestyle– and medical questionnaire data and mammograms were available for these women. Genotyping was done using the TaqMan PCR assay and mammographic density was assessed using a computer-assisted method. Means of mammographic density were compared by ESR1 genotypes and haplotypes. The percentage density was higher in women with one or two copies of the PvuII p allele (means for Pp and pp are 37% and 36%, respectively) than in those with the PP genotype (32%, Ptrend = 0.09). Women with one or two copies of the XbaI x allele had higher mean percentage density (Xx and xx, 36% and 37%, respectively) than those with the XX genotype (31%, Ptrend &lt; 0.01). Haplotype 1 (px) was associated with increased density, whereas haplotype 2 (PX) was associated with decreased density, both suggesting an allele-dose effect (Ptrend = 0.08 and &lt;0.01, respectively). Similar associations were found with absolute density (Ptrend &lt; 0.01). The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density.
Family History Assessment to Detect Increased Risk for Colorectal Cancer: Conceptual Considerations and a Preliminary Economic Analysis
Authors: Ramsey Scott D. , Burke Wylie , Pinsky Linda , Clarke Lauren , Newcomb Polly , Khoury Muin J. 
Published: March 2006

Abstract
Background: Although the rationale for earlier screening of persons with a family history of colorectal cancer is plausible, there is no direct evidence that earlier assessment is either effective or cost-effective.
Objective: To estimate the clinical and economic effect of using family history assessment to identify persons for colorectal cancer screening before age 50.
Methods: We developed a decision model to compare costs and outcomes for two scenarios: (a) standard population screening starting at age 50; (b) family history assessment at age 40, followed by screening colonoscopy at age 40 for those with a suggestive family history of colorectal cancer. The analysis was conducted using the health insurer perspective.
Results: Using U.S. population estimates, 22 million would be eligible for family history assessment, and one million would be eligible for early colonoscopy; 2,834 invasive cancers would be detected, and 29,331 life years would be gained. The initial program cost would be $900 million. The discounted cost per life year gained of family history assessment versus no assessment equals $58,228. The results were most sensitive to the life expectancy benefit from earlier screening, the cost of colonoscopy, and the relative risk of colon cancer in those with a family history.
Conclusions: The cost-effectiveness of family history assessment for colorectal cancer approaches that of other widely accepted technologies; yet, the results are sensitive to several assumptions where better data are needed. Because of the relatively high prevalence of family history in the population, careful analysis and empirical data are needed.
Methyl-CpG Binding Domain 1Gene Polymorphisms and Risk of Primary Lung Cancer
Authors: Jang Jin-Sung , Lee Su Jeong , Choi Jin Eun , Cha Sung Ick , Lee Eung Bae , Park Tae In , Kim Chang Ho , Lee Won Kee , Kam Sin , Choi Je-Yong , Kang Young Mo , Park Rang-Woon , Kim In-San , Cho Young Lae , Jung Tae Hoon , Han Sung Beom , Park Jae Yong 
Published: March 2006

AbstractThe methyl-CpG binding domain 1 (MBD1) protein plays an important role for transcriptional regulation of gene expression. Polymorphisms and haplotypes of the MBD1 gene may have an influence on MBD1 activity on gene expression profiles, thereby modulating an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of MBD1 −634G&gt;A, −501delT (−501 T/T, T/−, −/−), and Pro401Ala genotypes and their haplotypes with the risk of lung cancer in a Korean population. The MBD1 genotype was determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency matched for age and gender. The −634GG genotype was associated with a significantly increased risk of overall lung cancer compared with the −634AA genotype [adjusted odds ratio (OR), 3.10; 95% confidence interval (95% CI), 1.24-7.75; P = 0.016]. When analyses were stratified according to the tumor histology, the −634GG genotype was associated with a significantly increased risk of adenocarcinoma compared with the −634AA genotype (adjusted OR, 4.72; 95% CI, 1.61-13.82; P = 0.005). For the MBD1 −501delT and Pro401Ala polymorphisms, the −501 T/T genotype was associated with a marginal significantly increased risk of adenocarcinoma compared with the −501−/− genotype (adjusted OR, 2.07; 95% CI, 1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype (adjusted OR, 3.41; 95% CI, 1.21-9.60; P = 0.02). Consistent with the genotyping analyses, the −634G/−501T/401Pro haplotype was associated with a significantly increased risk of overall lung cancer and adenocarcinoma compared with the −634A/−501−/401Ala haplotype (adjusted OR, 1.44; 95% CI, 1.08-1.91; P = 0.012 and Pc = 0.048; adjusted OR, 1.75; 95% CI, 1.20-2.56; P = 0.004 and Pc = 0.016, respectively). On a promoter assay, the −634A allele had significantly higher promoter activity compared with the −634G allele in the Chinese hamster ovary cells and A549 cells (P &lt; 0.05 and P &lt; 0.001, respectively), but the −501delT polymorphism did not have an effect on the promoter activity. When comparing the promoter activity of the MBD1 haplotypes, the −634A/−501− haplotype had a significantly higher promoter activity than the −634G/−501T haplotype (P &lt; 0.001). These results suggest that the MBD1 −634G&gt;A, −501delT, and Pro401Ala polymorphisms and their haplotypes contribute to the genetic susceptibility for lung cancer and particularly for adenocarcinoma.