bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA Signature of Primary Pigmented Nodular Adrenocortical Disease: Clinical Correlations and Regulation of Wnt Signaling
Authors: Iliopoulos Dimitrios , Bimpaki Eirini I. , Nesterova Maria , Stratakis Constantine A. 
Published: April 2009

Abstract
MicroRNAs comprise a novel group of gene regulators implicated in the development of different types of cancer; however, their role in primary pigmented nodular adrenocortical disease (PPNAD) has not been investigated. PPNAD is a bilateral adrenal hyperplasia often associated with Carney complex, a multiple neoplasia syndrome; both disorders are caused by protein kinase A (PKA) regulatory subunit type 1A (PRKARIA)–inactivating mutations. We identified a 44-microRNA gene signature of PPNAD after comparing PPNAD with normal adrenal samples. Specifically, 33 microRNAs were up-regulated and 11 down-regulated in PPNAD relative to normal tissues. These results were validated by stem loop real-time PCR analysis. Comparison of microRNA microarray data with clinicopathologic variables revealed a negative correlation (r = −0.9499) between let-7b expression and cortisol levels in patients with PPNAD. Integration of microRNA microarray with serial analysis of gene expression data together with bioinformatic algorithm predictions revealed nine microRNA-gene target pairs with a potential role in adrenal pathogenesis. Using a PPNAD cell line, we showed that miR-449 was up-regulated and identified its direct target, WNT1-inducible signaling pathway protein 2 (WISP2); in addition, pharmacologic inhibition of PKA resulted in the up-regulation of miR-449 leading to the suppression of WISP2. Overall, we investigated, for the first time, the microRNA profile and its clinical significance in PPNAD; these data also suggest that PKA, via microRNA regulation, affects the Wnt signaling pathway, which through expression and clinical studies is suspected to be a primary mediator of PRKAR1A-related tumorigenesis. [Cancer Res 2009;69(8):3278–82]
Replication of the 10q11 and Xp11 Prostate Cancer Risk Variants: Results from a Utah Pedigree-Based Study
Authors: Camp Nicola J. , Farnham James M. , Wong Jathine , Christensen G. Bryce , Thomas Alun , Cannon-Albright Lisa A. 
Published: April 2009

Abstract
A recent genome-wide association study suggested seven new loci as associated with prostate cancer susceptibility. The strongest associated single nucleotide polymorphism (SNP) in each region was identified (rs2660753, rs9364554, rs6465657, rs10993994, rs7931342, rs2735839, rs5945619). We studied these seven SNPs in a replication study consisting of 169 familial prostate cancer cases selected from Utah high-risk prostate cancer pedigrees and 805 controls. We performed subset analyses for aggressive and early-onset prostate cancer. At a nominal significance level, two SNPs were found to be associated with prostate cancer: rs10993994 on chromosome 10q11 [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.05-1.90; P = 0.022] and rs5945619 on chromosome Xp11 (OR, 1.54; 95% CI, 1.03-2.31; P = 0.035). Restricting analysis to familial prostate cancer cases with aggressive disease yielded very similar risk estimates at both SNPs. However, subset analysis for familial, early-onset disease indicated highly significant association evidence and substantially higher risk estimates for rs10993994 (OR, 2.20; 95% CI, 1.48-3.27; P &lt; 0.0001). This result suggests that the higher risk estimates from the stage 1 cohort in the original study for rs10993994 may have been due to the early-onset and familial nature of the prostate cancer cases in that cohort. In conclusion, in a small case-control study of prostate cancer cases from Utah high-risk pedigrees, we have significantly replicated association of prostate cancer with rs10993994 (10q11) upon study-wide correction for multiple comparisons. We also nominally replicated the association of prostate cancer with rs5945619 (Xp11). In particular, it seems that the susceptibility locus at 10q11 maybe involved in familial, early-onset disease. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1290–4)
Genetic Models for the Familial Aggregation of Mammographic Breast Density
Authors: Kataoka Masako , Antoniou Antonis , Warren Ruth , Leyland Jean , Brown Judith , Audley Tina , Easton Doug 
Published: April 2009

Abstract
Background: Mammographic breast density (MBD) has a strong genetic component. Investigating the genetic models for mammographic density may provide further insights into the genetic factors affecting breast cancer risk.
Purpose: To evaluate the familial aggregation of MBD and investigate the genetic models of susceptibility.
Methods: We used data on 746 women from 305 families participating in the Sisters in Breast Screening study. Retrieved mammograms were digitized, and percent mammographic density was determined using the Cumulus software. Linear regression analysis was done to identify the factors that are associated with mammographic density and a multivariate regression model was constructed. Familial correlations between relative pairs were calculated using the residuals from these models. Genetic models of susceptibility were investigated using segregation analysis.
Results: After adjusting for covariates, the intraclass correlation coefficient among the residuals was 0.26 (95% confidence interval, 0.16-0.36) in sister-sister pairs and 0.67 (0.27-1.00) among the monozygotic twin pairs. The most parsimonious model was a Mendelian single major gene model in which an allele with population frequency 0.39 (95% confidence interval, 0.33-0.46) influenced mammographic density in an additive fashion. This model explained 66% of the residual variance.
Conclusion: These results confirm that MBD has a strong heritable basis, and suggest that major genes may explain some of the familial aggregation. These results may have implications for the search of genes that control mammographic density. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1277–84)
Afamin and Apolipoprotein A-IV: Novel Protein Markers for Ovarian Cancer
Authors: Dieplinger Hans , Ankerst Donna Pauler , Burges Alexander , Lenhard Miriam , Lingenhel Arno , Fineder Linda , Buchner Hannes , Stieber Petra 
Published: April 2009

Abstract
Comparative proteomics identified the vitamin E-binding plasma protein afamin as a potential novel tumor marker for ovarian cancer. In addition, we observed in a previous small study decreased plasma concentrations of apolipoprotein A-IV (apoA-IV) in preoperative patients with kidney cancer. The aim of this study was therefore to analyze afamin and apoA-IV in a large case-control study to evaluate the diagnostic utility of the two potential novel tumor markers in ovarian cancer patients. We measured plasma concentrations of afamin and apoA-IV by means of a specific sandwich-type ELISA using affinity-purified polyclonal and monoclonal antibodies in 181 ovarian cancer patients of various clinical stages, 399 patients with benign gynecologic diseases, including endometriosis, and 177 controls and compared results with those for the conventional ovarian cancer tumor marker cancer antigen 125 (CA125). Afamin concentrations decreased from a median of 70.7 mg/L (range, 34.6-116.1 mg/L) in healthy controls to 65.2 mg/L (range, 20.2-206.6 mg/L) in patients with benign gynecologic diseases to 56.0 mg/L (range, 4.7-96.0 mg/L) in ovarian cancer patients (P &lt; 0.001 for all pairwise comparisons). Similar results were obtained with apoA-IV concentrations decreasing from 13.0 mg/dL (range, 5.5-34.0 mg/dL) in controls to 11.7 mg/dL (range, 2.0-32.3 mg/dL) in benign conditions to 9.4 mg/dL (range, 0.3-29.5 mg/dL) in ovarian cancer (all P &lt; 0.001). Receiver operating characteristic analysis for differentiating ovarian cancer patients from healthy controls revealed for a specificity of 90% sensitivity values of 92.4%, 42.4%, and 40.8% for CA125, afamin, and apoA-IV, respectively. Afamin, but not apoA-IV, added independent diagnostic information to CA125 and age for differentiating ovarian cancer from benign and healthy samples; the odds ratio of ovarian cancer was reduced by 44% for each doubling of afamin (P = 0.032). The relatively low sensitivity, however, clearly indicates that afamin and apoA-IV alone are not sufficiently suitable as diagnostic markers for ovarian cancer. Afamin contributes, however, independent diagnostic information to CA125, thus establishing its potential as an adjunct marker to CA125. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1127–33)
Prenatal X-ray Exposure and Rhabdomyosarcoma in Children: A Report from the Children's Oncology Group
Authors: Grufferman Seymour , Ruymann Frederick , Ognjanovic Simona , Erhardt Erik B. , Maurer Harold M. 
Published: April 2009

AbstractThe association between antenatal diagnostic X-ray exposure and risk of rhabdomyosarcoma in children was assessed in a national case-control study of 319 rhabdomyosarcoma cases and 319 matched controls. Data were collected by telephone interviews of subjects' parents. Overall, an odds ratio (OR) of 1.9 [95% confidence interval (CI), 1.1-3.4] was found for any X-ray examination of the mother during pregnancy. Risk was greatest for X-ray exposure during the first trimester (OR, 5.7; 95% CI, 1.2-27.8) and was also increased for the third trimester (OR, 2.0; 95% CI, 0.9-4.6), whereas second trimester exposure was not associated with increased risk. A nonsignificant increase in risk was found for any X-rays of the abdomen, pelvis, chest, or back. Increased risk was significantly associated with “other” X-ray exposures (relative risk, 2.9; 95% CI, 1.1-7.7), primarily composed of dental X-rays. The association was strongest between embryonal rhabdomyosarcoma and first trimester exposure (relative risk, 10.5; 95% CI, 1.5-458.4). This observation regarding embryonal rhabdomyosarcoma, and our previous report of an increased frequency of major malformations in rhabdomyosarcoma are compatible with findings from animal studies in which Ptc heterozygous knockout mice exhibited an increased risk of radiation-induced development defects and of spontaneously occurring embryonal rhabdomyosarcoma. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1271–6)
Ductal Lavage in Women from BRCA1/2 Families: Is There a Future for Ductal Lavage in Women at Increased Genetic Risk of Breast Cancer?
Authors: Loud Jennifer T. , Thiébaut Anne C.M. , Abati Andrea D. , Filie Armando C. , Nichols Kathryn , Danforth David , Giusti Ruthann , Prindiville Sheila A. , Greene Mark H. 
Published: April 2009

Abstract
Purpose: Ductal lavage has been used for risk stratification and biomarker development and to identify intermediate endpoints for risk-reducing intervention trials. Little is known about patient characteristics associated with obtaining nipple aspirate fluid (NAF) and adequate cell counts (≥10 cells) in ductal lavage specimens from BRCA mutation carriers.
Methods: We evaluated patient characteristics associated with obtaining NAF and adequate cell counts in ductal lavage specimens from the largest cohort of women from BRCA families yet studied (BRCA1/2 = 146, mutation-negative = 23, untested = 2). Fisher's exact test was used to evaluate categorical variables; Wilcoxon nonparametric test was used to evaluate continuous variables associated with NAF or ductal lavage cell count adequacy. Logistic regression was used to identify independent correlates of NAF and ductal lavage cell count adequacy.
Results: From 171 women, 45 (26%) women had NAF and 70 (41%) women had ductal lavage samples with ≥10 cells. Postmenopausal women with intact ovaries compared with premenopausal women [odds ratio (OR), 4.8; P = 0.03] and women without a prior breast cancer history (OR, 5.2; P = 0.04) had an increased likelihood of yielding NAF. Having breast-fed (OR, 3.4; P = 0.001), the presence of NAF before ductal lavage (OR, 3.2; P = 0.003), and being premenopausal (OR, 3.0; P = 0.003) increased the likelihood of ductal lavage cell count adequacy. In known BRCA1/2 mutation carriers, only breast-feeding (OR, 2.5; P = 0.01) and the presence of NAF (OR, 3.0; P = 0.01) were independent correlates of ductal lavage cell count adequacy.
Conclusions: Ductal lavage is unlikely to be useful in breast cancer screening among BRCA1/2 mutation carriers because the procedure fails to yield adequate specimens sufficient for reliable cytologic diagnosis or to support translational research activities. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1243–51)
Serum Retinol and Prostate Cancer Risk: a Nested Case-Control Study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Schenk Jeannette M. , Riboli Elio , Chatterjee Nilanjan , Leitzmann Michael F. , Ahn Jiyoung , Albanes Demetrius , Reding Douglas J. , Wang Yinghui , Friesen Marlin D. , Hayes Richard B. , Peters Ulrike 
Published: April 2009

Abstract
Vitamin A (retinol) plays a key role in the regulation of cell growth and differentiation, and has been studied as a potential chemopreventive agent for prostate cancer. However, findings from epidemiologic studies on the association between circulating retinol concentrations and the risk of prostate cancer are inconsistent. We examined whether serum concentrations of retinol were associated with the risk of prostate cancer in a nested case-control study using 692 prostate cancer cases and 844 matched controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We estimated the risk of prostate cancer using multivariate, conditional logistic regression to calculate odds ratios and 95% confidence intervals for overall prostate cancer and aggressive disease (stage III or IV or Gleason &gt;7; n = 269). Serum retinol concentrations were not associated with overall prostate cancer risk; however, the highest versus lowest concentrations of serum retinol were associated with a 42% reduction in aggressive prostate cancer risk (Ptrend = 0.02), with the strongest inverse association for high-grade disease (Gleason sum &gt;7; odds ratio, 0.52; 95% confidence interval, 0.32-0.84; Ptrend = 0.01). Our results suggest that higher circulating concentrations of retinol are associated with a decreased risk of aggressive prostate cancer. Further research is needed to better understand the significance of elevations in serum retinol concentrations and the possible biological mechanisms through which retinol affects prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1227–31)
A Prospective Study of Relative Telomere Length and Postmenopausal Breast Cancer Risk
Authors: De Vivo Immaculata , Prescott Jennifer , Wong Jason Y.Y. , Kraft Peter , Hankinson Susan E. , Hunter David J. 
Published: April 2009

Abstract
During breast cancer progression, a substantial increase in chromosomal aberrations is observed in the transition from ductal hyperplasia to carcinoma in situ. Telomeres are essential structures to chromosomal integrity. Consequently, telomere dysfunction, which leads to genomic instability, is hypothesized to play a causal role in the progression of breast cancer. However, the few epidemiologic studies that have assessed the relationship between telomere length and breast cancer risk have been inconsistent. We used quantitative real-time PCR to measure relative telomere length in genomic DNA extracted from peripheral blood leukocytes and examined its association with postmenopausal breast cancer risk in 1,122 invasive breast cancer cases and 1,147 matched controls free of diagnosed cancer nested within the prospective Nurses' Health Study. Our data show that relative telomere length was not associated with a significant elevation in postmenopausal breast cancer risk [below versus above median; odds ratio, 1.23; 95% confidence interval, 0.94-1.60; Ptrend = 0.20]. Estrone and estradiol hormone levels were significantly inversely associated with relative telomere length (P = 0.02). Other established breast cancer risk factors such as family history of breast cancer and history of benign breast disease were not associated with relative telomere length in separate linear regression models each adjusted for age and disease status (P ≥ 0.07). Our results provide little support for an important role of telomere length, as measured in peripheral blood leukocytes, as a biomarker of breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1152–6)
The Association between Diabetes, Insulin Use, and Colorectal Cancer among Whites and African Americans
Authors: Vinikoor Lisa C. , Long Millie D. , Keku Temitope O. , Martin Christopher F. , Galanko Joseph A. , Sandler Robert S. 
Published: April 2009

Abstract
Colorectal cancer and diabetes are common diseases that share many risk factors. It has been hypothesized that diabetes is a risk factor for colorectal cancer. We used two large population-based case-control studies from North Carolina to determine whether diabetes and/or insulin therapy was associated with colon cancer and/or rectal cancer (defined as cancer of the sigmoid colon, rectosigmoid, or rectum) and whether this association differed by race. Cases and matched controls from the North Carolina Colon Cancer Studies I and II were interviewed about demographics, dietary factors, diagnosis of diabetes, and use of medications to treat diabetes. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Colon and rectal cancer cases reported a higher prevalence of diabetes than their respective control groups. Compared with Whites without diabetes, Whites with diabetes had adjusted ORs of 1.40 (95% CI, 0.93-2.12) for colon cancer and 1.38 (95% CI, 1.00-1.90) for rectal cancer. Diabetes was not associated with colon or rectal cancer among African Americans [OR, 1.17 (95% CI, 0.81-1.70) and 0.75 (95% CI, 0.44-1.28), respectively]. Among Whites with diabetes, insulin use was positively associated with rectal cancer. The same association was not seen for African American diabetics using insulin; however, the number of African Americans using insulin was small. In sum, diabetes was positively associated with rectal cancer and approached a positive association with colon cancer among Whites. No association was present among African Americans. Insulin use was also positively associated with rectal cancer among Whites. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1239–42)
Performance of Prediction Models for BRCA Mutation Carriage in Three Racial/Ethnic Groups: Findings from the Northern California Breast Cancer Family Registry
Authors: Kurian Allison W. , Gong Gail D. , John Esther M. , Miron Alexander , Felberg Anna , Phipps Amanda I. , West Dee W. , Whittemore Alice S. 
Published: April 2009

Abstract
Purpose: Patients with early-onset breast and/or ovarian cancer frequently wish to know if they inherited a mutation in one of the cancer susceptibility genes, BRCA1 or BRCA2. Accurate carrier prediction models are needed to target costly testing. Two widely used models, BRCAPRO and BOADICEA, were developed using data from non-Hispanic Whites (NHW), but their accuracies have not been evaluated in other racial/ethnic populations.
Methods: We evaluated the BRCAPRO and BOADICEA models in a population-based series of African American, Hispanic, and NHW breast cancer patients tested for BRCA1 and BRCA2 mutations. We assessed model calibration by evaluating observed versus predicted mutations and attribute diagrams, and model discrimination using areas under the receiver operating characteristic curves.
Results: Both models were well-calibrated within each racial/ethnic group, with some exceptions. BOADICEA overpredicted mutations in African Americans and older NHWs, and BRCAPRO underpredicted in Hispanics. In all racial/ethnic groups, the models overpredicted in cases whose personal and family histories indicated &gt;80% probability of carriage. The two models showed similar discrimination in each racial/ethnic group, discriminating least well in Hispanics. For example, BRCAPRO's areas under the receiver operating characteristic curves were 83% (95% confidence interval, 63-93%) for NHWs, compared with 74% (59-85%) for African Americans and 58% (45-70%) for Hispanics.
Conclusions: The poor performance of the model for Hispanics may be due to model misspecification in this racial/ethnic group. However, it may also reflect racial/ethnic differences in the distributions of personal and family histories among breast cancer cases in the Northern California population. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1084–91)
The Impact of HER2/neuExpression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02
Authors: Benavides Linda C. , Gates Jeremy D. , Carmichael Mark G. , Patel Ritesh , Holmes Jarrod P. , Hueman Matthew T. , Mittendorf Elizabeth A. , Craig Dianna , Stojadinovic Alexander , Ponniah Sathibalan , Peoples George E. 
Published: April 2009

AbstractPurpose: HER2/neu, a source of immunogenic peptides, is expressed in &gt;75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed.Experimental Design: Patients were stratified by HER2/neu expression. Low expressors (n = 100) were defined as HER2/neu immunohistochemistry (IHC) 1+ to 2+ or fluorescence in situ hybridization &lt; 2.0. Overexpressors (n = 51) were defined as IHC 3+ or fluorescence in situ hybridization ≥ 2.0. Additional analyses were done stratifying by IHC status (0-3+). Standard clinocopathlogic factors, immunologic response (in vivo delayed-type hypersensitivity reactions; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay), and clinical responses (recurrence; mortality) were assessed.Results: Low-expressor (control, 44; vaccinated, 56) versus overexpressor patients (control, 22; vaccinated, 29) were assessed. Low expressors, overexpressors, and most IHC-status vaccinated groups responded immunologically. Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients (P = 0.04), and vaccinated IHC 1+ patients had increased long-term immune response (P = 0.08). More importantly, compared with controls, low-expressor patients had a mortality reduction (P = 0.08). The largest decrease in mortality was seen in IHC 1+ patients (P = 0.05). In addition, a subset of overexpressor patients (n = 7) received trastuzumab before vaccination, and this combination seems safe and immunologically beneficial.Conclusions: Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination. The low expressors, specifically IHC 1+ patients, had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine.