bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus and Breast Cancer: State of the Evidence for Viral Carcinogenesis
Authors: Glaser Sally L. , Hsu Joe L. , Gulley Margaret L. 
Published: June 2022

Abstract
As the etiology and progression of breast cancer remain incompletely understood, novel routes of disease pathogenesis are important to consider. Viral pathogens have not been much explored, but recent interest has focused on Epstein-Barr virus (EBV). Studies of an association of this ubiquitous herpesvirus with breast cancer have had notably inconsistent results, marked by varying EBV presence (from 0% to 50% of tumors) and the absence of certain viral characteristics found in other EBV-related malignancies. The research has been plagued by the technical challenges of localizing EBV to tumor cells and by a tendency to overlook epidemiological cofactors, shown in all other EBV-related cancers to impact the EBV association. Breast cancer studies to date have used several viral detection methods of varying or uncertain sensitivity and specificity; most have involved small and/or poorly characterized case series and paid insufficient attention to epidemiological cofactors relevant to breast cancer and to EBV-related malignancies. Given these limitations and the established complexity of the connection of EBV with other cancers, a definitive judgment regarding the presence of this virus in breast cancer cannot yet be rendered. Recent advances in laboratory methodologies should help overcome the challenges of EBV detection in breast cancers. Further research is warranted, given the potential for an EBV association to inform not only breast cancer etiology but also early detection, treatment, and prevention.
A Prospective Study of Breast Cancer Risk Using Routine Mammographic Breast Density Measurements
Authors: Vacek Pamela M. , Geller Berta M. 
Published: June 2022

Abstract
Mammographic breast density is a major risk factor for breast cancer but estimates of the relative risk associated with differing density patterns have varied widely. It is also unclear how menopausal status influences this association and to what extent the effects of density are due to its correlation with other risk factors. Most recent investigations of breast density have been case-control studies, which provide indirect estimates of relative risk. We have prospectively followed 61,844 women for an average of 3.1 years to directly estimate risk among women in the four mammographic breast density categories defined by the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS). The study was population-based and used density assessments routinely made by community radiologists. Cox regression was used to obtain age-adjusted relative risk estimates and to control for other risk factors. Risk increased with density and the risk associated with extremely dense breasts, relative to entirely fatty breasts, was 4.6 (95% confidence interval, 1.7–12.6) for premenopausal women and 3.9 (95% confidence interval, 2.6–5.8) for postmenopausal women. Estimates for pre- and postmenopausal women did not differ significantly. Although breast density was significantly related to body mass index, age at first childbirth, and postmenopausal hormone use (P &lt; 0.001), adjustment for these variables only slightly altered the relative risk estimates. Our results correspond well to those from case-control studies using more quantitative measures of mammographic breast density and suggest that routine Breast Imaging Reporting and Data System density measurements may be useful in models for assessing breast cancer risk in individual women.
What Factors Are Associated with Diagnostic Follow-Up after Abnormal Mammograms? Findings from a U.S. National Survey
Authors: Yabroff K. Robin , Breen Nancy , Vernon Sally W. , Meissner Helen I. , Freedman Andrew N. , Ballard-Barbash Rachel 
Published: June 2022

Abstract
The purpose of this study was to identify factors associated with diagnostic follow-up after an abnormal mammogram in a national sample of women in the U.S. The sample was selected from the year 2000 National Health Interview Survey and included 1901 women aged 30 and above who reported ever having an abnormal mammogram. The outcome measure was receipt of at least some diagnostic follow-up after an abnormal mammogram. Bivariate and multivariate logistic regression analyses were used to explore the associations between sociodemographic characteristics, general health and health behaviors, cancer risk and risk perceptions, and health care utilization characteristics and follow-up. Approximately 9% of women who reported ever having abnormal mammograms reported not completing any additional diagnostic follow-up. Controlling for all other factors, women with less than a high school education were less likely to report follow-up after an abnormal mammogram than were women who had at least completed college (odds ratio = 0.56; 95% confidence interval: 0.32, 0.98). Younger women and women in poorer health were also less likely to report follow-up. Women who perceived a high versus low level of cancer in their family were more likely to report follow-up (odds ratio = 1.65; 95% confidence interval: 1.04, 2.62), controlling for all other factors. In a national sample of women with abnormal mammograms, a substantial number did not complete any diagnostic follow-up, potentially reducing the effectiveness of mammography screening programs in the U.S. Additional research on subsequent screening behaviors for women with incomplete follow-up and in-depth exploration of the roles of patient-provider interactions and health care system factors related to the index abnormal mammogram is warranted.
Fertility Intentions Following Testing for a BRCA1 Gene Mutation
Authors: Smith Ken R. , Ellington Lee , Chan Anna Y. , Croyle Robert T. , Botkin Jeffrey R. 
Published: June 2022

Abstract
Objective: To test whether fertility intentions differed among persons who tested positive, tested negative, or did not know their genetic status for a mutation of the BRCA1 gene. Method: Participants were members of a large Utah-based kindred with an identified mutation at the BRCA1 locus. Participants received genetic counseling prior to testing and were interviewed at baseline before testing and at three points after receiving test results from a genetic counselor. The sample included men and women who completed all interviews, were between ages 18 and 45, and were fertile, resulting in a sample of 101 respondents. The primary dependent variable measured whether a subject indicated that they were moderately or very sure at all three post-testing interviews that they intended to have additional children. Effects of BRCA1 mutation status on fertility intentions were estimated using multivariate logistic regressions where we controlled for gender, age, marital status, and baseline fertility intentions. Results: Female carriers were less likely to want additional children in relation to female noncarriers (odds ratio 0.12, 95% confidence interval 0.01–1.23; P = 0.074). No differences were found among men. There was a significant difference in the effect of mutation status on fertility intentions between males and females (Gender × Carrier status interaction; P = 0.009). Persons who did not know their mutation status were less likely to want more children than noncarriers (odds ratio 0.09, 95% confidence interval 0.01–0.75; P = 0.027). Conclusion: Predictive genetic testing for late-onset cancer susceptibility affects family planning decision-making. Persons contemplating predictive testing should be informed about possible effects such testing may have on their plans for future fertility.
Increased Plasma Levels of Insulin-Like Growth Factor 2 and Insulin-Like Growth Factor Binding Protein 3 Are Associated with Endometrial Cancer Risk
Authors: Oh Jonathan C. , Wu Weiguo , Tortolero-Luna Guillermo , Broaddus Russell , Gershenson David M. , Burke Thomas W. , Schmandt Rosemarie , Lu Karen H. 
Published: June 2022

Abstract
Circulating insulin-like growth factors (IGFs) and their binding proteins have been associated with increased risk of breast, prostate, colon, and lung cancer. To examine the association of IGFs and endometrial cancer risk, we measured the plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with endometrial cancer and 80 age-matched control subjects with no history of cancer. Mean plasma levels of IGF-2 were significantly higher in women with cancer versus controls (670 ng/ml versus 380 ng/ml, P &lt; 0.001). In contrast, significantly lower mean plasma levels of IGF-1 (155 mg/ml versus 185 ng/ml, P &lt; 0.01) and IGFBP-3 (1703 ng/ml versus 2170 ng/ml, P &lt; 0.001) were observed among cases compared to the control group. Women in the highest quartile of IGF-2 were found to have 9.67 (95% confidence interval 3.29–28.43) times the risk of endometrial cancer than women in the lowest quartiles. Women in the highest quartile of IGFBP-3 were associated with a significantly decreased risk for developing endometrial cancer (odds ratio = 0.23, 95% confidence interval 0.09–0.60). These data suggest that increased plasma levels of IGF-2 and decreased levels of IGFBP-3 are associated with an increased risk of endometrial cancer. Further validation of these results is needed to determine the potential usefulness of risk assessment.
High-Throughput Association Testing on DNA Pools to Identify Genetic Variants that Confer Susceptibility to Acute Myeloid Leukemia
Authors: Rollinson Sara , Allan James M. , Law Graham R. , Roddam Philippa L. , Smith Martyn T. , Skibola Christine , Smith Alexandra G. , Forrest Matthew S. , Sibley Kathryn , Higuchi Russell , Germer Soren , Morgan Gareth J. 
Published: June 2022

Abstract
We have evaluated the use of allele-specific PCR (AS PCR) on DNA pools as a tool for screening inherited genetic variants that may be associated with risk of adult acute myeloid leukemia (AML). Two DNA pools were constructed, one of 444 AML cases, and another of 823 matched controls. The pools were validated using individual genotyping data for GSTP1 and LTα variants. Allele frequencies for variants in GSTP1 and LTα were estimated using quantitative AS PCR, and when compared to individual genotyping data, a high degree of concordance was seen. AS primer pairs were designed for nine candidate genetic variants in DNA repair and cell cycle/apoptotic regulatory genes, including Cyclin D1 [codon 870 splice site variant (A&gt;G)]; BRCA1, P871L; ERCC2, K751Q; FAS −1377 (G&gt;A); hMLH1 −93 (G&gt;A) and V219I; p21, S31R; and the XRCC1 R194W and R399Q variants. For six of these assays, there was at least 95% concordance between AS PCR genotyping and an alternative approach carried out on individual samples. Furthermore, these six AS PCR assays all accurately estimated allele frequencies in the pools that had been calculated using individual genotyping data. A significant disease association was seen with AML for the −1377 variant in FAS (odds ratio 1.76, 95% confidence interval 1.26–2.44). These data suggest that quantitative AS PCR can be used as an efficient screening technique for disease associations of genetic variants in DNA pools made from case-control studies.
Identifying Functional Genetic Variants in DNA Repair Pathway Using Protein Conservation Analysis
Authors: Savas Sevtap , Kim David Y. , Ahmad M. Farhan , Shariff Mehjabeen , Ozcelik Hilmi 
Published: June 2022

Abstract
The role of DNA repair in initiation, promotion, and progression of malignancy suggests that variations in DNA repair genes confer altered cancer risk. Accordingly, DNA repair gene variants have been studied extensively in the context of cancer predisposition. Single nucleotide polymorphisms (SNPs) are the most common genetic variations in the human genome. A fraction of SNPs are located within the genes, which are likely to alter the gene expression and function. SNPs that change the encoded amino acid sequence of the proteins (non-synonymous; nsSNPs) are potentially genetic disease determinant variations. However, as not all amino acid substitutions are supposed to lead to a change in protein function, it will be necessary to have a priori prediction and determination of the functional consequences of amino acid substitutions per se, and then together with other genetic and environmental factors to study their possible association with a trait. Here we report the analysis of nsSNPs in 88 DNA repair genes and their functional evaluation based on the conservation of amino acids among the protein family members. Our analysis demonstrated that &gt;30% of variants of DNA repair proteins are highly likely to affect the function of the proteins drastically. In this study, we have shown that three nsSNPs, which were predicted to have functional consequences (XRCC1-R399Q, XRCC3-T241M, XRCC1-R280H), were already found to be associated with cancer risk. The strategy developed and applied in this study has the potential to identify functional protein variants of DNA repair pathway that may be associated with cancer predisposition.
Food and Botanical Groupings and Risk of Breast Cancer: A Case-Control Study in Shanghai, China
Authors: Shannon Jackilen , Ray Roberta , Wu Chenyuan , Nelson Zakia , Gao Dao Li , Li Wenjin , Hu Wei , Lampe Johanna , Horner Neilann , Satia Jessie , Patterson Ruth , Fitzgibbons Dawn , Porter Peggy , Thomas David 
Published: June 2022

Abstract
Breast cancer incidence rates more than double in Chinese women as they migrate from China to Hong Kong to the United States, suggesting that environmental factors contribute to the international variation in breast cancer incidence. Several dietary factors, which differ between the United States and the Chinese population, including intake of soy, meat, and fruits and vegetables, have been suggested to affect breast cancer risk. This report describes results from a case-control study of diet and risk of breast cancer nested in a randomized trial of breast self exam in Shanghai, China. Participating breast cancer cases (n = 378) and frequency age-matched controls (n = 1,070) completed a comprehensive food frequency questionnaire and a risk factor questionnaire. After adjustment for age, total energy intake, and total years of breast-feeding, women in the highest quartile of fruit and vegetable intake (≥3.8 servings/d) were significantly less likely to have breast cancer (odds ratio, 0.48; 95% confidence interval, 0.29-0.78) as compared with women in the lowest quartile of intake (≤2.3 servings/d). Egg consumption was also significantly inversely associated with risk of breast cancer (odds ratio for ≥6.0 eggs/wk versus ≤2.0 eggs/wk is 0.56; 95% confidence interval, 0.35-0.91). There was no difference in soy consumption between cases and controls. None of the associations with a single botanical family explained the strong inverse relationship between fruits and vegetables and breast cancer risk. These results provide additional evidence in support of the important role of fruits and vegetables in breast cancer prevention.
Micronuclei as Biomarkers of Carcinogen Exposure in Populations Exposed to Arsenic Through Drinking Water in West Bengal, India: A Comparative Study in Three Cell Types
Authors: Basu Anamika , Ghosh Pritha , Das Jayanta K. , Banerjee Apurba , Ray Kunal , Giri Ashok K. 
Published: June 2022

Abstract
Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 ± 9.0273 μg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 ± 0.3157 μg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P &lt; 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells.
Effects of Reduced Cigarette Smoking on Levels of 1-Hydroxypyrene in Urine
Authors: Hecht Stephen S. , Carmella Steven G. , Le Ky-Anh , Murphy Sharon E. , Li Y. Shelby , Le Chap , Jensen Joni , Hatsukami Dorothy K. 
Published: June 2022

Abstract
We investigated the effects of smoking fewer cigarettes/day (CPD) on urinary levels of 1-hydroxypyrene (1-HOP), a biomarker of carcinogenic polycyclic aromatic hydrocarbon (PAH) uptake. We randomly assigned 151 smokers to either a reduction group or a waitlist group. In the reduction group, we measured urinary 1-HOP at two baseline intervals. Then, the smokers were expected to reduce their CPD by 25% in weeks 0–2, 50% in weeks 2–4, and 75% in weeks 4–6 and to maintain reduced smoking through week 26. In the waitlist group, four baseline measurements were taken and then the smokers joined the reduction group. Urinary 1-HOP was quantified at weeks 4, 6, 8, 12, and 26 after baseline. Statistically significant reductions in urinary 1-HOP were observed at most time points examined in groups of smokers who reduced to different extents. Reductions in the waitlist group were also generally significantly greater than baseline levels. The reductions in 1-HOP were usually modest (ranging from 14% to 35% in all groups and time points examined), which partially reflects the fact that there are sources of pyrene exposure other than cigarette smoke. Thus, cessation of smoking would only be expected to result in partial reductions of 1-HOP. The observed reductions in 1-HOP were not fully consistent with reductions in CPD probably due to uncontrolled dietary factors. Collectively, the results demonstrate that some smokers can achieve substantial reductions in 1-HOP, reflecting reduced uptake of polycyclic aromatic hydrocarbons, by reducing CPD, but there was not a consistent relationship between these parameters.
Predictors of Participation in Psychosocial Telephone Counseling following Genetic Testing for BRCA1 and BRCA2 Mutations
Authors: Halbert Chanita Hughes , Wenzel Lari , Lerman Caryn , Peshkin Beth N. , Narod Steven , Marcus Alfred , Corio Camille , Demarco Tiffani , Bellamy Scarlett 
Published: June 2022

Abstract
Although adjunctive educational and psychosocial programs are now being developed for BRCA1 and BRCA2 (BRCA1/2) mutation carriers, limited information is available about whether mutation carriers will want to receive such programs or about the characteristics of individuals who participate. The goals of the present study were to describe rates of completing a psychosocial telephone counseling (PTC) intervention that was offered to female BRCA1/2 mutation carriers and to identify sociodemographic and psychological factors associated with decisions to complete the intervention. Subjects were 66 BRCA1/2 mutation carriers who were randomized to receive a PTC intervention following receipt of genetic test results. Sociodemographic and psychological factors were evaluated before notification of assignment to the PTC intervention. Completion of the intervention was determined from study records. Overall, 75.8% of subjects completed the PTC intervention. Compared to unaffected subjects, those affected with breast and/or ovarian cancer were 76% less likely to complete the intervention [odds ratio (OR) = 0.24, 95% confidence interval (CI) = 0.06, 0.98, P = 0.05]. In addition, subjects with higher levels of cancer-specific distress [OR = 4.74, 95% CI = 1.02, 22.03, P = 0.05] and those with greater perceptions of social support [OR = 5.81, 95% CI = 1.29, 26.16, P = 0.02] were also most likely to complete the intervention. The results of this study suggest that while most BRCA1/2 mutation carriers are likely to complete an adjunctive psycho-educational program, personal history of cancer, cancer-specific distress, and perceptions of social support are likely to influence participation.
Methylated DNA Collected by Tampons—A New Tool to Detect Endometrial Cancer
Authors: Fiegl Heidi , Gattringer Conny , Widschwendter Andreas , Schneitter Alois , Ramoni Angela , Sarlay Daniela , Gaugg Inge , Goebel Georg , Müller Hannes M. , Mueller-Holzner Elisabeth , Marth Christian , Widschwendter Martin 
Published: June 2022

Abstract
This proof of principle study aimed to define a new and simple strategy for detection of endometrial cancer using epigenetic markers. We investigated DNA isolated from vaginal secretion collected from tampon for aberrant methylation of five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15 patients with endometrial cancer and 109 patients without endometrial cancer. All endometrial cancer patients revealed three or more methylated genes, whereas 91% (99 of 109) of the patients without endometrial cancer had no or fewer than three genes methylated in their vaginal secretion. The methods developed in this study provide the basis for a prospective clinical trial to screen asymptomatic women who are at high risk for endometrial cancer.
Polymorphisms in PTGS1 (=COX-1) and Risk of Colorectal Polyps
Authors: Ulrich Cornelia M. , Bigler Jeannette , Sparks Rachel , Whitton John , Sibert Justin G. , Goode Ellen L. , Yasui Yutaka , Potter John D. 
Published: June 2022

Abstract
Two isoforms of prostaglandin H synthase (PTGS = COX) are key enzymes in prostaglandin synthesis and primary targets for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Use of aspirin or other NSAIDs is associated with a lower risk and reduced recurrence of colorectal adenomas, established precursors of adenocarcinoma. This study investigated risk of colorectal adenomatous and hyperplastic polyps associated with several polymorphisms in the coding region of PTGS1. Within the Minnesota polyp case-control study, patients with colorectal adenomatous (n = 521) or hyperplastic (n = 194) polyps and n = 621 polyp-free controls were genotyped for four PTGS1 polymorphisms (R8W, L15-L16del, P17L, L237M); these had been predicted to affect protein function based on sequence-homology software. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed. Whereas there was no appreciable difference in adenoma or hyperplastic polyp risk associated with R8W, P17L, and L237M, an increased risk was observed for individuals heterozygous for the L15-L16del polymorphism (OR = 3.6, 95% CI 1.2–11.2). The variant L15-L16del allele appeared to be associated with a stronger increase in adenoma risk among nonusers of aspirin/other NSAIDs. The reduced risk observed with aspirin/other NSAID use was limited to those wild type for P17L [PP users: OR = 0.6 (0.5–0.8) versus PP nonusers: 1.0 (referent) (P interaction = 0.03)]. To our knowledge, this study represents the first investigation of polymorphisms in PTGS1 and risk of colorectal polyps. The L15-L16del variant allele may result in an increased risk of colorectal adenomas, whereas P17L may be relevant to the pharmacogenetics of aspirin. These preliminary findings require confirmation in larger studies of colorectal neoplasia.