bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transvaginal Ultrasound Measurement of Endometrial Thickness as a Biomarker for Estrogen Exposure
Authors: Sit Anita S.Y. , Modugno Francesmary , Hill Lyndon M. , Martin Jerry , Weissfeld Joel L. 
Published: June 2022

Abstract
Objective: In clinical settings, transvaginal ultrasound has been used to evaluate abnormal vaginal bleeding. Because the endometrium responds to estrogens, endometrial thickness may constitute a biomarker of estrogen status in postmenopausal women. This study aimed to validate the transvaginal ultrasonographic measurement of endometrial thickness as an estrogen biomarker in asymptomatic, postmenopausal women by demonstrating an association between endometrial thickness and risk factors known to be associated with estrogen exposure. Method: Endometrial thickness was measured in 1,271 women ages 55 to 74 years who underwent transvaginal ultrasound screening as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A questionnaire, completed before screening, provided risk factor information, including reproductive and hormone use histories. Results: Endometrial thickness measurements ranged from 1 to 32 mm (median 3.0 mm). The frequencies of thicker endometrium (≥3.0 mm), according to body mass index (BMI) quartile, were 55.2%, 66.1%, 69.7%, and 76.7% (P &lt; 0.0001). The frequencies of thicker endometrium were 57.8%, 58.3%, and 82.6% among never users, ex-users, and current users of hormone replacement therapy (HRT), respectively (P &lt; 0.0001). Other factors associated with thicker endometrium included age, marital status, history of uterine fibroids, years since menopause, and history of hypertension. Statistically significant associations were not seen in analyses limited to current HRT users (n = 461). In multiple variable analysis (R2 = 0.08), current HRT use (P &lt; 0.0001) and higher BMI (P &lt; 0.0001) were independently associated with thicker endometrium. Conclusion: In postmenopausal women, factors reflecting exogenous (current HRT use) and endogenous (BMI) estrogen exposure were associated with increased endometrial thickness as measured during screening transvaginal ultrasound. Practical limitations related to screening transvaginal ultrasound include measurement variability, lack of information regarding type or dose of HRT, and problems of differentiating true endometrial thickening from unrecognized endometrial polyps or fluid accumulations. Constrained by these limitations, these results partially validate a transvaginal ultrasound measurement of endometrial thickness as a potential biomarker related to estrogen status.
BRCAPAP: Feasibility of Clinical BRCA Testing on Liquid-Based Cervical Cytology: Implications for Biomarker Development
Authors: Muller Carolyn Y. , Schorge John O. , Tomlinson Gail E. , Ashfaq Raheela 
Published: June 2022

Abstract
Objective: The study was designed to test the feasibility that lower genital tract cytology is a compatible medium for robust germ line genetic analyses. Method: BRCA1 and/or BRCA2 gene mutational analysis was done on DNA isolated from liquid-based cervical or vaginal cytology taken from 17 consenting women (age 29–65 years) who previously had genetic counseling followed by BRACAnalysis (Myriad Genetics, Salt Lake City, UT) blood analyses. Eleven women had known mutations in either BRCA1 or BRCA2 (cases) and six had no identified mutations (controls) on entry into the study. Anonymized cytology samples were sent to Myriad Genetics with a request for testing that was limited to the degree of genomic testing previously done on the blood samples. Results: One cervicovaginal specimen from a test-positive woman had inadequate cellular content that precluded gene sequencing and therefore was excluded from this analysis. For the 16 women with adequate cytologic specimens, there was 100% concordance for BRCA mutation test results between blood and genital tract cytology (κ = 1.0; 95% confidence interval, 0.51–1.0). Conclusion: We have shown the feasibility of using liquid-based genital tract cytology as an alternative biospecimen to blood for germ line genetic analysis using a clinical approved assay. It needs to be emphasized that any type of testing for BRCA1 or BRCA2 mutation genotype should only be done in the setting of pretest and posttest counseling.
Prostate-Specific Antigen and Free Prostate-Specific Antigen in the Early Detection of Prostate Cancer: Do Combination Tests Improve Detection?
Authors: Etzioni Ruth , Falcon Seth , Gann Peter H. , Kooperberg Charles L. , Penson David F. , Stampfer Meir J. 
Published: June 2022

AbstractBackground: The combined use of free and total prostate-specific antigen (PSA) in early detection of prostate cancer has been controversial. This article systematically evaluates the discriminating capacity of a large number of combination tests. Methods: Free and total PSA were analyzed in stored serum samples taken prior to diagnosis in 429 cases and 1,640 controls from the Physicians' Health Study. We used a classification algorithm called logic regression to search for clinically useful tests combining total and percent free PSA and receiver operating characteristic analysis and compared these tests with those based on total and complexed PSA. Data were divided into training and test subsets. For robustness, we considered 35 test-train splits of the original data and computed receiver operating characteristic curves for each test data set. Results: The average area under the receiver operating characteristic curve across test data sets was 0.74 for total PSA and 0.76 for the combination tests. Combination tests with higher sensitivity and specificity than PSA &gt; 4.0 ng/mL were identified 29 out of 35 times. All these tests extended the PSA reflex range to below 4.0 ng/mL. Receiver operating characteristic curve analysis indicated that the overall diagnostic performance as expressed by the area under the curve did not differ significantly for the different tests. Conclusions: Tests combining total and percent free PSA show modest overall improvements over total PSA. However, utilization of percent free PSA below a PSA threshold of 4 ng/mL could translate into a practically important reduction in unnecessary biopsies without sacrificing cancers detected.
Circulating Endogenous Retinoic Acid Concentrations among Participants Enrolled in a Randomized Placebo-Controlled Clinical Trial of Retinyl Palmitate
Authors: Sedjo Rebecca L. , Ranger-Moore James , Foote Janet , Craft Neal E. , Alberts David S. , Xu Min-Jian , Giuliano Anna R. 
Published: June 2022

Abstract
Retinoids have been studied extensively for their chemopreventive properties. The biological activity of retinoids is acquired through their conversion to retinoic acid (RA). Characterization of endogenous circulating RA concentrations after supplementation with vitamin A over longer time periods has not been done previously. Our investigation was conducted to determine whether vitamin A (retinyl palmitate) supplementation significantly increases circulating RA concentrations of all-trans-, 9-cis-, and 13-cis-RA. Using plasma samples from 41 participants enrolled in a randomized clinical trial of placebo, 25,000, 50,000, or 75,000 IU supplemental retinyl palmitate daily, high-performance liquid chromatography analyses were conducted for concentrations of three RA isomers. Seven plasma samples were analyzed for each participant over a 16-month period. Based on an intention-to-treat analysis, results obtained using linear mixed models showed that supplementation with retinyl palmitate statistically significantly increased concentrations of all three RA isomers from baseline levels. This study suggests that supplementation with retinyl palmitate is an effective means to increase circulating all-trans, 9-cis-, and 13-cis-RA concentrations among humans.
Differential Peroxisome Proliferator-Activated Receptor-γ Isoform Expression and Agonist Effects in Normal and Malignant Prostate Cells
Authors: Subbarayan Vemparala , Sabichi Anita L. , Kim Jeri , Llansa Norma , Logothetis Christopher J. , Lippman Scott M. , Menter David G. 
Published: June 2022

Abstract
Peroxisome proliferator-activated receptor-γ (PPAR-γ) is being studied intensively for its role in carcinogenesis and in mediating the effects of prostate cancer treatment and prevention drugs. Prostate cancers express abundant and higher constitutive levels of PPAR-γ than do normal prostate cells and are growth inhibited by ligand activation of PPAR-γ. However, little is known about the role of PPARs in tumorigenesis or in normal prostate epithelial cells (EC). We examined the expression, phosphorylation patterns, and functions of the human PPAR (hPPAR)-γ1 and hPPAR-γ2 isoforms in normal prostate ECs to determine if activation of the receptor is sufficient for PPAR-γ ligand activity in prostate cells. We found that ECs did not express either PPAR-γ1 or PPAR-γ2 protein and were not sensitive to growth inhibition by the PPAR-γ ligand 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). In contrast, prostate cancer cells (PC-3), which express PPAR-γ1 receptor isoform, are growth inhibited by PPAR-γ ligand. Forced expression of hPPAR-γ1 or hPPAR-γ2 made ECs sensitive to 15d-PGJ2 and led to reduced cellular viability. The direct repeat-1 promoter containing PPAR response elements was transactivated in ECs expressing exogenous PPAR-γ1 or PPAR-γ2, indicating that either isoform can be active in these cells. 15-Lipoxygenase-2, expressed at high levels in ECs, was down-regulated by transfecting PPAR-γ expression construct (either γ1 or γ2 isoform) into ECs. Addition of PPAR-γ ligand 15-hydroxyeicosatetraenoic acid in the presence of PPAR-γ expression caused further down-regulation of 15-lipoxygenase-2. Our data illustrate that a PPAR-γ ligand (15d-PGJ2) activates PPAR-γ1 and selectively induces cell death in human prostate cancer cells but not in normal prostate ECs. These findings have important implications for the development of PPAR-γ-targeting agents that prevent or treat prostate cancer and spare normal prostate cells.
The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary Intervention Strategies
Authors: Voskuil Dorien W. , Vrieling Alina , van't Veer Laura J. , Kampman Ellen , Rookus Matti A. 
Published: June 2022

Abstract
The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk as well as the experimental evidence for a causal relation between the endocrine IGF system and tumor growth. The potential for dietary intervention to alter the IGF system and thereby cancer risk is supported by several lines of evidence. Postulated mechanisms of action are as follows: (a) reduction of levels of circulating IGF-I, which will decrease activation of the IGF-I receptor and subsequent signaling pathways; (b) increasing local IGF binding proteins, which may have IGF-dependent effects through obstruction of IGF interaction with local IGF-I receptor as well as IGF-independent effects; and (c) interference with estrogens and estrogen receptor action, which may have direct (and possibly synergistic) effects on IGF signaling. An overview is given of the epidemiologic studies on dietary determinants of circulating IGF-I. Examples of dietary factors, such as dairy protein, lycopene, and phytoestrogens, are used to illustrate the potential mode of action of dietary interventions that may act on the IGF system. In conclusion, the IGF system has every potential to serve as an intermediate for cancer (chemo)prevention studies. On the short term, more research initiatives aimed at the effects of specific food components or dietary strategies on the IGF system both in animal models and in humans are warranted.
Effect of Black Tea Intake on the Excretion of Mutagens in the Urine of Volunteers Taking a Beef Meal
Authors: Yoxall Vikki R. , Bishop Jacquie , Ioannides Costas 
Published: June 2022

Abstract
The objective of this study was to investigate in a crossover study conducted in human volunteers whether black tea intake modulates the metabolism of heterocyclic amines, consumed in the form of well-cooked beefburgers, as exemplified by the excretion of mutagens in the urine. Mutagens were extracted from urine with blue rayon, and mutagenic activity was determined in the Ames test, in the presence of an activation system derived from Aroclor 1254–induced rats, and employing the Salmonella typhimurium O-acetylase over-expressing YG1024 bacterial strain. Volunteers consumed three well-cooked beefburgers, whereas a concurrently cooked fourth burger was analyzed for mutagenic activity. Following intake of the burgers, an increase in urinary mutagenic activity was observed, and mutagenic activity was completely excreted within 24 hours. A good correlation was obtained between the intake and excretion of mutagenic activity. The volunteers consumed the same burger meal on two different occasions, once following intake of 10 cups of strong black tea, and the second following intake of a corresponding volume of water. Urine was collected by each volunteer for 24 hours after the meal, and compliance was ascertained utilizing the excretion of p-aminobenzoic acid. The mutagenic ratio, defined as the ratio of urinary mutagenicity over the intake of mutagenicity, was not altered by the black tea, being 0.142 and 0.135 during the water and tea intake, respectively. It is inferred that short-term intake of high levels of black tea, as part of an otherwise normal diet, does not modulate the human metabolism of heterocyclic amines.
Differences in Breast Cancer Risk Factors by Tumor Marker Subtypes among Premenopausal Vietnamese and Chinese Women
Authors: Nichols Hazel B. , Trentham-Dietz Amy , Love Richard R. , Hampton John M. , Hoang Anh Pham Thi , Allred D. Craig , Mohsin Syed K. , Newcomb Polly A. 
Published: June 2022

Abstract
We evaluated associations between reproductive and lifestyle risk factors with breast cancer tumor marker status in a case-control study. Cases were premenopausal women living in Vietnam and China who were eligible for a clinical trial of oophorectomy and tamoxifen as treatment for breast cancer (n = 682). Controls were nonrelative hospital visitors, matched on age to the cases (n = 649). Immunohistochemical analysis was used to identify the presence of estrogen receptor (ER) and progesterone receptor and the overexpression of HER-2/neu oncogene. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression, adjusted for known confounders. Overall, 280 (61%) tumor samples were ER positive and 176 (38%) were ER negative. HER-2/neu overexpression was detected in 161 (35%) samples, whereas 286 (26%) samples were HER-2/neu negative. We observed an inverse trend between increasing parity and decreasing breast cancer risk (P = 0.002). Women ages ≥25 years at first birth had increased breast cancer risk compared with women ages &lt;25 years at first birth (OR, 1.53; 95% CI, 1.20-1.95). Women who consumed alcohol had increased risk of breast cancer compared with women who did not (OR,1.85; 95% CI, 1.32-2.61). Compared with controls, OR estimates for breast cancer by parity and age at first birth were significantly associated with ER and/or HER-2/neu tumor status by Wald test (P &lt; 0.05). Family history, age at menarche, cumulative lactation, body mass index, and education were not significantly related to breast cancer risk. Our findings support the hypothesis that some breast cancer risk factors differ by ER and HER-2/neu tumor marker subtypes.
T29C Polymorphism in the Transforming Growth Factor β1 Gene and Postmenopausal Breast Cancer Risk: The Multiethnic Cohort Study
Authors: Marchand Loı̈c Le , Haiman Christopher A. , van den Berg David , Wilkens Lynne R. , Kolonel Laurence N. , Henderson Brian E. 
Published: June 2022

Abstract
Laboratory studies suggest a dual role for the transforming growth factor-β (TGF-β) signaling pathway in breast cancer. The normal antiproliferative activity of TGF-β in early breast tumor development is replaced by a promoting effect in later stages. A T29C transition polymorphism in the TGFB1 gene has been associated with higher circulating TGF-β1 levels, and inconsistently with breast cancer risk in three recent studies. We tested the association of this variant with invasive breast cancer in a case-control study of 1123 cases and 2314 controls nested in the Multiethnic Cohort (MEC) Study. This study is a large prospective study being conducted in Hawaii and Los Angeles that includes Japanese, white, African American, Latino, and Native Hawaiian women who were predominantly postmenopausal at baseline. After adjustment for breast cancer risk factors, the odds ratio (OR) and 95% confidence interval (95% CI) for the TGFB1 29 CC genotype was 0.95 (95% confidence interval: 0.76–1.18), compared to the TT genotype. Analyses stratified by race/ethnicity, stage, or age category did not reveal any association of this variant with breast cancer. Given the strong biological rationale and the scarce and divergent epidemiologic data to date, additional investigations of the relationship between breast cancer and genetic variants in the TGF-β signaling pathway appear warranted.
Breast Cancer Risk and Exposure in Early Life to Polycyclic Aromatic Hydrocarbons Using Total Suspended Particulates as a Proxy Measure
Authors: Bonner Matthew R. , Han Daikwon , Nie Jing , Rogerson Peter , Vena John E. , Muti Paola , Trevisan Maurizio , Edge Stephen B. , Freudenheim Jo L. 
Published: June 2022

AbstractPolycyclic aromatic hydrocarbons (PAH) are ubiquitous in the environment. We hypothesized that early life exposure to PAHs may have particular importance in the etiology of breast cancer. We conducted a population-based, case-control study of ambient exposure to PAHs in early life in relation to the risk of breast cancer. Total suspended particulates (TSP), a measure of ambient air pollution, was used as a proxy for PAHs exposure. Cases (n = 1,166) were women with histologically confirmed, primary, incident breast cancer. Controls (n = 2,105) were frequency matched by age, race, and county of residence to cases. Annual average TSP concentrations (1959-1997) by location were obtained from the New York State Department of Environmental Conservation for Erie and Niagara Counties. Based on the monitor readings, prediction maps of TSP concentrations were generated with ArcGIS 8.0 (ESRI, Inc., Redlands, CA) using inverse distance squared weighted interpolation. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. In postmenopausal women, exposure to high concentrations of TSP (&gt;140 μg/m3) at birth was associated with an adjusted odds ratio of 2.42 (95% confidence interval, 0.97-6.09) compared with exposure to low concentrations (&lt;84 μg/m3). However, in premenopausal women, where exposures were generally lower, the results were inconsistent with our hypothesis and in some instances were suggestive of a reduction in the risk of breast cancer. Our study suggests that exposure in early life to high levels of PAHs may increase the risk of postmenopausal breast cancer; however, other confounders related to geography cannot be ruled out.
Compliance of Average- and Intermediate-Risk Women to Semiannual Ovarian Cancer Screening
Authors: Drescher Charles W. , Nelson Judy , Peacock Sue , Andersen M. Robyn , McIntosh Martin W. , Urban Nicole 
Published: June 2022

Abstract
Objective: To report rates of compliance with an ovarian cancer screening protocol using serum CA125 and transvaginal sonography (TVS), performed semiannually on an alternating schedule, among participants at average or intermediate risk for developing ovarian cancer. Methods: Two hundred ninety-two women at average or intermediate risk for developing ovarian cancer were randomly assigned to arms of a controlled clinical trial in which they received ovarian cancer screening consisting of serum CA125 alternating with TVS performed semiannually over 18 months, either alone or in combination with ovarian cancer risk education. A computerized tracking system generated screening appointment reminder letters and monitored adherence to scheduled screening. Participants overdue for scheduled screens received follow-up telephone calls consisting of up to four reminder messages left at 1-week intervals, and one to two interim attempts to reach participants between messages. The compliance rate for each screen was calculated as a ratio of the number of participants successfully completing the screen relative to the number expected to attend. Compliance rate by screen was: screen 1 (CA125) (97.3%), screen 2 (TVS) (82.5%), screen 3 (CA125) (79.0%), and screen 4 (TVS) (64.5%). One hundred seventy-two women completed all four screens and were classified as adherent to the screening protocol. Analysis by screening modality suggests that participants were more compliant to screens involving CA125. Age, educational background, distance from screening center, personal or family history of cancer, perceived risk of ovarian cancer, pre-enrollment ovarian cancer screening behavior, receiving an abnormal screen test result, and participation in ovarian cancer risk education sessions were not associated with adherence to the screening protocol or compliance to any of the screens. Conclusions: Despite extensive follow-up, compliance of average- and intermediate-risk women to an ovarian cancer screening protocol requiring semiannual screening diminishes rapidly. We propose that a semiannual ovarian cancer screening protocol, particularly one including TVS, may be too intensive for use in this population.
DNA Damage in Patients Infected by Helicobacter pylori
Authors: Ladeira Marcelo S.P. , Rodrigues Maria A.M. , Salvadori Daisy M.F. , Queiroz Dulciene M.M. , Freire-Maia Dértia V. 
Published: June 2022

Abstract
Helicobacter pylori (H. pylori) is considered to predispose carriers to gastric cancer but its role on gastric carcinogenesis is still unknown. The aim of this study was to investigate DNA damage by the comet assay in gastric epithelial cells from antrum and corpus in H. pylori-infected patients with gastritis of different degrees. H. pylori status, gastric histology, and DNA damage were studied in 62 H. pylori-infected and 18 non-infected patients, all of them non-smokers, non-alcoholics, and non-drug users. DNA damage was significantly higher in H. pylori-infected patients presenting gastritis than in non-infected patients with normal mucosa. A direct correlation between the levels of DNA damage and the intensity of gastritis was observed in H. pylori-infected patients. Association between DNA damage and age was also found. The levels of DNA damage were significantly higher in patients older than 50 years than in younger patients with the same degree of gastritis. Our results indicate that H. pylori infection is associated with DNA damage in gastric epithelial cells, which could be a biomarker of risk for gastric cancer in humans.