bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of HIV-1 Integration in
Ex Vivo
-Infected CD4 T Cells from Elite Controllers
Authors: Buzon Maria J. , Seiss Katherine , Weiss Robert , Brass Abraham L. , Rosenberg Eric S. , Pereyra Florencia , Yu Xu G. , Lichterfeld Mathias 
Published: July 2011

ABSTRACT

Elite controllers spontaneously maintain undetectable levels of HIV-1 replication for reasons that remain unclear. Here, we show that in elite controllers, direct
ex vivo
infection of purified CD4 T cells without prior
in vitro
activation results in disproportionately low levels of integrated HIV-1 DNA relative to the quantity of reverse transcripts, while the levels of two-long terminal repeat (2-LTR) circles were excessively elevated relative to those of integrated HIV-1 DNA. This indicates that chromosomal HIV-1 integration is inhibited in
ex vivo-
infected CD4 T cells from elite controllers. This defect in HIV-1 integration was unrelated to p21, a host protein that can restrict early HIV-1 replication steps, and was not visible following infection of
in vitro-
activated CD4 T cells from elite controllers. These data contribute to increasing evidence that intrinsic inhibition of specific HIV-1 replication steps plays an important role in the ability of elite controllers to maintain undetectable viral loads.
CXCR3 Enhances a T-Cell–Dependent Epidermal Proliferative Response and Promotes Skin Tumorigenesis
Authors: Winkler Ashley E. , Brotman Joshua J. , Pittman Meredith E. , Judd Nancy P. , Lewis James S. , Schreiber Robert D. , Uppaluri Ravindra 
Published: July 2011

Abstract
The chemokine receptor CXCR3 has been proposed to play a critical role in host antitumor responses. In this study, we defined CXCR3-expressing immune cell infiltration in human skin squamous cell carcinomas and then used CXCR3-deficient mice to assess the contribution of CXCR3 to skin tumorigenesis. Our studies employed two established protocols for chemical skin carcinogenesis [methylcholanthrene (MCA) or 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) models]. CXCR3 deletion did not affect tumor development in the MCA model; however, CXCR3 was important in the DMBA/TPA model where gene deletion reduced the incidence of skin tumors. This decreased incidence of skin tumors did not reflect differences in epidermal development but rather was associated with reduced epidermal thickness and proliferation in CXCR3−/− mice, implicating the CXCR3 pathway in DMBA/TPA-induced epidermal inflammation and proliferation. Notably, CXCR3 expressed in CD4+ and CD8+ T cells was found to be important for enhanced epidermal proliferation. Specifically, CXCR3-deficient mice reconstituted with T cells isolated from wild-type mice treated with DMBA/TPA restored wild-type levels of epidermal proliferation in the mutant mice. Taken together, our findings establish that CXCR3 promotes epidermal tumorigenesis likely through a T-cell–dependent induction of keratinocyte proliferation. Cancer Res; 71(17); 5707–16. ©2011 AACR.
Volume of Mammographic Density and Risk of Breast Cancer
Authors: Shepherd John A. , Kerlikowske Karla , Ma Lin , Duewer Frederick , Fan Bo , Wang Jeff , Malkov Serghei , Vittinghoff Eric , Cummings Steven R. 
Published: July 2011

Abstract
Background: Assessing the volume of mammographic density might more accurately reflect the amount of breast volume at risk of malignant transformation and provide a stronger indication of risk of breast cancer than methods based on qualitative scores or dense breast area.
Methods: We prospectively collected mammograms for women undergoing screening mammography. We determined the diagnosis of subsequent invasive or ductal carcinoma in situ for 275 cases, selected 825 controls matched for age, ethnicity, and mammography system, and assessed three measures of breast density: percent dense area, fibroglandular volume, and percent fibroglandular volume.
Results: After adjustment for familial breast cancer history, body mass index, history of breast biopsy, and age at first live birth, the ORs for breast cancer risk in the highest versus lowest measurement quintiles were 2.5 (95% CI: 1.5–4.3) for percent dense area, 2.9 (95% CI: 1.7–4.9) for fibroglandular volume, and 4.1 (95% CI: 2.3–7.2) for percent fibroglandular volume. Net reclassification indexes for density measures plus risk factors versus risk factors alone were 9.6% (P = 0.07) for percent dense area, 21.1% (P = 0.0001) for fibroglandular volume, and 14.8% (P = 0.004) for percent fibroglandular volume. Fibroglandular volume improved the categorical risk classification of 1 in 5 women for both women with and without breast cancer.
Conclusion: Volumetric measures of breast density are more accurate predictors of breast cancer risk than risk factors alone and than percent dense area.
Impact: Risk models including dense fibroglandular volume may more accurately predict breast cancer risk than current risk models. Cancer Epidemiol Biomarkers Prev; 20(7); 1473–82. ©2011 AACR.
Risks for Persistence and Progression by Human Papillomavirus Type 16 Variant Lineages Among a Population-Based Sample of Danish Women
Authors: Gheit Tarik , Cornet Iris , Clifford Gary M. , Iftner Thomas , Munk Christian , Tommasino Massimo , Kjaer Susanne K. 
Published: July 2011

Abstract
Background: Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role.
Methods: HPV16-positive women with normal cytology in a large Danish cohort were reassessed for HPV16 status at 2 years and followed-up for cervical intraepithelial neoplasia 3 or worse (CIN3+) over 11 years through linkage with a national pathology database. Relative risks for clearance, persistence, and progression were compared with different HPV16 variant lineages based upon E6 gene sequencing.
Results: Sixty-two (23.7%) of 261 HPV16 infections were persistent at 2 years, and 32 (51.6%) persistent infections progressed to CIN3+. The majority of baseline infections belonged to the European lineage (97.3%), with EUR-350T and EUR-350G accounting for 61.3% and 36.0% of infections, respectively. At two years, the proportion of HPV16 infections that persisted was significantly higher for EUR-350T (28.2%) than EUR-350G (15.9%) variants (odds ratio = 2.06, 95% CI, 1.04–4.25). This increased risk for persistence was consistent both in the absence (OR = 2.16, 95% CI, 0.84–6.26) or presence (OR = 1.89, 95% CI, 0.76–5.15) of progression to CIN3+. Among persistent HPV16 infections, there was no significant difference in risk of progression to CIN3+ between EUR-350T and EUR-350G sub-lineages, which were both associated with a substantial absolute risk (&gt;50%) of CIN3+.
Conclusions: Significant differences in risk for persistence exist between the HPV16 variants that predominate in Europe.
Impact: Understanding the genetic basis of HPV16 persistence and carcinogenicity may help unravel important interactions between HPV16 and the host immune system. Cancer Epidemiol Biomarkers Prev; 20(7); 1315–21. ©2011 AACR.
Polymorphisms in CYP1A1 and Ethnic-Specific Susceptibility to Acute Lymphoblastic Leukemia in Children
Authors: Swinney Ryan M. , Beuten Joke , Collier Anderson B. , Chen Tina T.-L. , Winick Naomi J. , Pollock Brad H. , Tomlinson Gail E. 
Published: July 2011

Abstract
Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL.
Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case–control analysis in Caucasian, Hispanic, and African-American children.
Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18–5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43–7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27–5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13–5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40–7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P &lt; 0.0001) and African Americans (P = 0.005).
Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population.
Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins. Cancer Epidemiol Biomarkers Prev; 20(7); 1537–42. ©2011 AACR.
Does Exposure to Asbestos Cause Ovarian Cancer? A Systematic Literature Review and Meta-analysis
Authors: Reid Alison , de Klerk Nick , Musk Arthur W. (Bill) 
Published: July 2011

Abstract
Introduction: The asbestos and ovarian cancer relationship is not well understood because of small numbers of women exposed to asbestos, small numbers of cases, and misclassification of peritoneal mesothelioma as ovarian cancer on death certificates. The aim of this study was to conduct a meta-analysis to quantify the evidence that exposure to asbestos causes ovarian cancer.
Methods: Fourteen cohort and two case-control studies were identified in Medline searches from 1950 to 2008.
Results: Statistically significant excess mortality was reported in four of the cohort studies, all of which determined their outcomes from the death certificate. Peritoneal mesotheliomas were reported in these studies, two of which reexamined pathology specimens and reported disease misclassification. Exposure-response relationships were inconsistent. When all studies were included in a meta-analysis, the effect size was 1.75 (95% CI, 1.45–2.10) attenuating to 1.29 (95% CI, 0.97–1.73) in studies with confirmed ovarian cancers.
Conclusion: Taken without further analysis, women thought to have ovarian cancer had an increased rate in the meta-analysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification. Cancer Epidemiol Biomarkers Prev; 20(7); 1287–95. ©2011 AACR.
Racial Differences in Colorectal Cancer Incidence and Mortality in the Women's Health Initiative
Authors: Simon Michael S. , Thomson Cynthia A. , Pettijohn Erin , Kato Ikuko , Rodabough Rebecca J. , Lane Dorothy , Hubbell F. Allan , O'Sullivan Mary Jo , Adams-Campbell Lucille , Mouton Charles P. , Abrams Judith , Chlebowski Rowan T. 
Published: July 2011

AbstractBackground: Colorectal cancer (CRC) incidence and mortality rates are higher in African–Americans as compared with other racial/ethnic groups. The women's health initiative (WHI) study sample was used to determine whether differences in CRC risk factors explain racial/ethnic differences in incidence and mortality.Methods: The WHI is a longitudinal study of postmenopausal women recruited from 40 centers. Baseline questionnaires were used to collect sociodemographic and health status information. All CRC diagnoses were centrally adjudicated. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by race/ethnicity.Results: The study sample included 131,481 (83.7%) White, 14,323 (9.1%) African–American, 6,362 (4.1%) Hispanic, 694 (0.4%) Native American and 4,148 (2.6%) Asian/Pacific Islanders. After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was the highest in African–Americans (annualized rate = 0.14%), followed by Whites and Native Americans (0.12% each), Asian/Pacific Islanders (0.10%), and Hispanics (0.08%). After adjustment for age and trial assignment, Hispanics had a lower risk compared with Whites, HR 0.73 (95% CI: 0.54–0.97) (P = 0.03), and African–Americans had a marginally greater risk, HR 1.16 (95% CI: 0.99–1.34), P = 0.06. Multivariable adjustment attenuated the difference in incidence between African–Americans and Whites (HR 0.99, 95% CI: 0.82–1.20), while strengthening the lower HR for Hispanics (HR 0.68, 95% CI: 0.48–0.97).Conclusions: African–American/White differences in CRC risk are likely due to sociodemographic/cultural factors other than race.Impact: A number of modifiable exposures could be a focus for reducing CRC risk in African–Americans. Cancer Epidemiol Biomarkers Prev; 20(7); 1368–78. ©2011 AACR.
MicroRNA Signatures: Novel Biomarker for Colorectal Cancer?
Authors: Luo Xiaoya , Burwinkel Barbara , Tao Sha , Brenner Hermann 
Published: July 2011

Abstract
Aberrant microRNA (miRNA) expression might be of potential use as diagnostic and prognostic biomarker for cancers. We reviewed studies published until March 2011 which assessed expression of miRNAs in colorectal cancer (CRC)/adenoma tissue and normal colorectal mucosa and in plasma of CRC/adenoma patients and healthy controls. Overall, 20 studies that investigated miRNA expression in tissue and 3 studies that investigated miRNA levels in plasma were included. A total of 160 miRNAs were found to be dysregulated in CRC. MiR-20a and miR-31 were found to be significantly upregulated in more than one study, and miR-143 and miR-145 were found to be significantly downregulated in CRC tissue in six or more studies. MiR-92a was significantly upregulated in CRC patients in two of the plasma-based studies and in CRC tissue in one of the tissue-based studies. Our results provide timely and relevant information for miRNAs as potential diagnostic biomarkers for CRC. The expression of miRNAs in plasma may be indicative of presence of CRC. Larger diagnostic studies are needed to evaluate potential use of miRNA expression in early detection and diagnosis of CRC. Cancer Epidemiol Biomarkers Prev; 20(7); 1272–86. ©2011 AACR.
Estrogen Metabolism and Exposure in a Genotypic–Phenotypic Model for Breast Cancer Risk Prediction
Authors: Crooke Philip S. , Justenhoven Christina , Brauch Hiltrud , Dawling Sheila , Roodi Nady , Higginbotham Kathryn S. P. , Plummer W. Dale , Schuyler Peggy A. , Sanders Melinda E. , Page David L. , Smith Jeffrey R. , Dupont William D. , Parl Fritz F. 
Published: July 2011

AbstractBackground: Current models of breast cancer risk prediction do not directly reflect mammary estrogen metabolism or genetic variability in exposure to carcinogenic estrogen metabolites.Methods: We developed a model that simulates the kinetic effect of genetic variants of the enzymes CYP1A1, CYP1B1, and COMT on the production of the main carcinogenic estrogen metabolite, 4-hydroxyestradiol (4-OHE2), expressed as area under the curve metric (4-OHE2-AUC). The model also incorporates phenotypic factors (age, body mass index, hormone replacement therapy, oral contraceptives, and family history), which plausibly influence estrogen metabolism and the production of 4-OHE2. We applied the model to two independent, population-based breast cancer case–control groups, the German GENICA study (967 cases, 971 controls) and the Nashville Breast Cohort (NBC; 465 cases, 885 controls).Results: In the GENICA study, premenopausal women at the 90th percentile of 4-OHE2-AUC among control subjects had a risk of breast cancer that was 2.30 times that of women at the 10th control 4-OHE2-AUC percentile (95% CI: 1.7–3.2, P = 2.9 × 10−7). This relative risk was 1.89 (95% CI: 1.5–2.4, P = 2.2 × 10−8) in postmenopausal women. In the NBC, this relative risk in postmenopausal women was 1.81 (95% CI: 1.3–2.6, P = 7.6 × 10−4), which increased to 1.83 (95% CI: 1.4–2.3, P = 9.5 × 10−7) when a history of proliferative breast disease was included in the model.Conclusions: The model combines genotypic and phenotypic factors involved in carcinogenic estrogen metabolite production and cumulative estrogen exposure to predict breast cancer risk.Impact: The estrogen carcinogenesis–based model has the potential to provide personalized risk estimates. Cancer Epidemiol Biomarkers Prev; 20(7); 1502–15. ©2011 AACR.
Validation of a Light Questionnaire with Real-life Photopic Illuminance Measurements: the Harvard Light Exposure Assessment Questionnaire
Authors: Bajaj Archna , Rosner Bernard , Lockley Steven W. , Schernhammer Eva S. 
Published: July 2011

Abstract
Background: Shift work, which necessitates light exposure at night, is now considered a probable carcinogen. To study the effects of light on chronic diseases like cancer, methods to measure light exposure in large observational studies are needed. We aimed to investigate the validity of self-reported current light exposure.
Methods: We developed a self-administered semiquantitative light questionnaire, the Harvard Light Exposure Assessment (H-LEA) questionnaire, and compared photopic scores derived from this questionnaire with actual photopic and circadian measures obtained from a real-life 7-day light meter application among 132 women (85 rotating night shift workers and 47 day workers) participating in the Nurses' Health Study II.
Results: After adjustment for age, body mass index (BMI), collection day, and night work status, the overall partial Spearman correlation between self-report of light exposure and actual photopic light measurements was 0.72 (P &lt; 0.001; Kendall τ = 0.57) and 0.73 (P &lt; 0.0001; Kendall τ = 0.58) when correlating circadian light measurements. There were only minimal differences in accuracy of self-report of light exposure and photopic or “circadian” light measurement between day (r = 0.77 and 0.78, respectively) and rotating night shift workers (r = 0.68 and 0.69, respectively).
Conclusions: The results of this study provide evidence of the criterion validity of self-reported light exposure using the H-LEA questionnaire.
Impact: This questionnaire is a practical method of assessing light exposure in large-scale epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 20(7); 1341–9. ©2011 AACR.
State Disparities in Colorectal Cancer Mortality Patterns in the United States
Authors: Naishadham Deepa , Lansdorp-Vogelaar Iris , Siegel Rebecca , Cokkinides Vilma , Jemal Ahmedin 
Published: July 2011

Abstract
Background: Colorectal cancer (CRC) mortality rates have been decreasing for many decades in the United States, with the decrease accelerating in the most recent time period. The extent to which this decrease varies across states and its influence on the geographic patterns of rates is unknown.
Methods: We analyzed the temporal trend in age-standardized CRC death rates for each state from 1990 to 2007 using joinpoint regression. We also examined the change in death rates between 1990–1994 and 2003–2007 using rate ratios with 95% confidence intervals and illustrated the change in pattern using maps. The relationship between the change in mortality rates and CRC screening rates for 2004 by state was examined using Pearson's correlation.
Results: CRC mortality rates significantly decreased in all states except Mississippi between 1990 and 2007 based on the joinpoint model. The decrease in death rates between 1990–1994 and 2003–2007 ranged from 9% in Alabama to greater than 33% in Massachusetts, Rhode Island, New York, and Alaska; Mississippi and Wyoming showed no significant decrease. Generally, the northeastern states showed the largest decreases, whereas southern states showed the smallest decreases. The highest CRC mortality rates shifted from the northeastern states during 1990 to 1994 to the southern states along the Appalachian corridor during 2003 to 2007. The decrease in CRC mortality rates by state correlated strongly with uptake of screening (r = −0.65, P &lt; 0.0001).
Conclusions: Progress in reducing CRC mortality varies across states, with the Northeast showing the most progress and the South showing the least progress.
Impact: These findings highlight the need for wider dissemination of CRC screening. Cancer Epidemiol Biomarkers Prev; 20(7); 1296–302. ©2011 AACR.
Chemokine RANTES Promoter Dimorphisms and Hepatocellular Carcinoma Occurrence in Patients with Alcoholic or Hepatitis C Virus–Related Cirrhosis
Authors: Charni Faten , Sutton Angela , Rufat Pierre , Laguillier Christelle , Mansouri Abdellah , Moreau Richard , Ganne-Carrié Nathalie , Trinchet Jean-Claude , Beaugrand Michel , Charnaux Nathalie , Nahon Pierre 
Published: July 2011

Abstract
Background: This study explores the influence of two functional genetic polymorphisms in the regulated on activation in normal T-cell expressed and secreted(RANTES) promoter on the risk of hepatocellular carcinoma (HCC) occurrence in patients with alcoholic or Hepatitis C Virus (HCV)-related cirrhosis.
Methods: RANTES C-28G and G-403A promoter dimorphisms and RANTES serum levels were assessed in 243 HCV-infected patients and 253 alcoholic patients, included at the time of diagnosis of cirrhosis and prospectively followed-up.
Results: During a mean follow-up time of 76 months, 137 (27.6%) patients developed HCC and 170 (34.2%) died or were transplanted. During follow-up, patients with alcoholic cirrhosis and bearing two copies of the RANTES G-403 variant (2G-403 genotype, n = 156/253) had a higher rate of HCC occurrence compared with patients carrying at least one RANTES A-403 allele (26.3% vs. 8.2%, P = 0.0004). The RANTES 2G-403 genotype was a risk factor for HCC occurrence [HR = 3.0 (1.3–5.8); first quartile time to HCC occurrence: 60 vs. 120 months; LogRank = 0.007] and death [HR = 1.4 (1.0–2.0); median time to death: 55 vs. 79 months; LogRank = 0.01] in this subgroup. Carriage of the RANTES 2G-403 genotype was not associated with HCC development or death in patients with HCV-related cirrhosis. The RANTES C-28G dimorphism did not influence the occurrence of death or HCC in either cohort of patients.
Conclusion: This study suggests an influence of the chemokine RANTES G-403A dimorphism on the occurrence of HCC in patients with alcoholic cirrhosis.
Impact: Our findings provide clues for future studies on RANTES gene in relation to HCC susceptibility. Cancer Epidemiol Biomarkers Prev; 20(7); 1439–46. ©2011 AACR.
Age-Period-Cohort Models in Cancer Surveillance Research: Ready for Prime Time?
Authors: Rosenberg Philip S. , Anderson William F. 
Published: July 2011

AbstractStandard descriptive methods for the analysis of cancer surveillance data include canonical plots based on the lexis diagram, directly age-standardized rates (ASR), estimated annual percentage change (EAPC), and joinpoint regression. The age-period-cohort (APC) model has been used less often. Here, we argue that it merits much broader use. First, we describe close connections between estimable functions of the model parameters and standard quantities such as the ASR, EAPC, and joinpoints. Estimable functions have the added value of being fully adjusted for period and cohort effects, and generally more precise. Second, the APC model provides the descriptive epidemiologist with powerful new tools, including rigorous statistical methods for comparative analyses, and the ability to project the future burden of cancer. We illustrate these principles by using invasive female breast cancer incidence in the United States, but these concepts apply equally well to other cancer sites for incidence or mortality. Cancer Epidemiol Biomarkers Prev; 20(7); 1263–8. ©2011 AACR.