bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Quality of Exfoliated Cervical Cells: Implications for Molecular Epidemiology and Biomarker Discovery
Authors: Habis Angelique H. , Vernon Suzanne D. , Lee Daisy R. , Verma Mukesh , Unger Elizabeth R. 
Published: June 2022

Abstract
The biologic sample collected in molecular epidemiology studies must accurately reflect the disease being studied and have sufficient molecular quality for the intended assays. Noninvasive sampling methods, such as scrapes or brushes, are increasingly used. In this study, we evaluate the impact of sample collection media and extraction methods on the quality and yield of RNA from routine exfoliated cervical cytology. Excess cellular material remaining on the cytologic collection device after preparation of the routine screening Papanicolaou smear was placed in a variety of collection media and extracted using two commercial kits. The collection media had the largest impact on the yield and quality of RNA as evaluated by denaturing agarose gel electrophoresis and image analysis. Two collection media, PAXgene and PreservCyt, yielded RNA from most samples. The RNA showed some degree of degradation as evidenced by the reduced size of the higher molecular weight ribosomal band. However, with a sensitive gold particle-based detection method, reproducible microarray results were obtained using this RNA.
Fear, Anxiety, Worry, and Breast Cancer Screening Behavior: A Critical Review
Authors: Consedine Nathan S. , Magai Carol , Krivoshekova Yulia S. , Ryzewicz Lynn , Neugut Alfred I. 
Published: June 2022

Abstract
Anxiety, fear, and worry are variously described as facilitators and barriers of breast cancer screening. However, several contradictions are evident in this research. A review article described the literature regarding the relations among fear, anxiety, and worry, along with emotion regulatory styles, and breast cancer screening behaviors before critiquing it in an attempt to uncover preliminary explanations for these discrepancies. Three main conclusions are drawn. First, it is suggested that researchers need to clearly define the components of cancer and the screening process that women are afraid of as each may bear a different relation to screening behavior. Second, greater care needs to be taken to employ psychometrically valid and reliable measures of fear and anxiety. Third, studies need to more systematically test findings across the minority and ethnic groups at greatest risk. A framework is presented and suggestions regarding the continued development of this promising area of research are made.
Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer?
Authors: Kim Young-In 
Published: June 2022

Abstract
Epidemiological, clinical, and animal studies collectively indicate that dietary folate intake and blood folate levels are inversely associated with colorectal cancer risk. Folate plays an essential role in one-carbon transfer involving remethylation of homocysteine to methionine, which is a precursor of S-adenosylmethionine, the primary methyl group donor for most biological methylations. DNA methylation is an important epigenetic determinant in gene expression, maintenance of DNA integrity and stability, chromosomal modifications, and development of mutations. Dysregulation and aberrant patterns of DNA methylation are generally considered to be mechanistically involved in colorectal carcinogenesis. Aberrant DNA methylation has been considered as a leading mechanism by which folate deficiency enhances colorectal carcinogenesis. However, currently available data pertaining to the effects of folate deficiency on DNA methylation are inconsistent and incomplete. The portfolio of evidence from animal, human, and in vitro studies suggests that the effects of folate deficiency on DNA methylation are highly complex; appear to depend on cell type, target organ, and stage of transformation; and are gene and site specific. In addition, the pattern of site- and gene-specific DNA methylation induced by folate deficiency may not be in concert with the direction of changes in genomic DNA methylation. Collectively, currently available evidence indicates that genomic DNA hypomethylation in the colorectum is not a probable mechanism by which folate deficiency enhances colorectal carcinogenesis. However, there is still a possibility that sequence-specific alterations of DNA methylation in critical cancer-related genes might be mechanistically involved in the folate deficiency-mediated colorectal carcinogenesis.
Interaction between Genetic Variations in DNA Repair Genes and Plasma Folate on Breast Cancer Risk
Authors: Han Jiali , Hankinson Susan E. , Zhang Shumin M. , De Vivo Immaculata , Hunter David J. 
Published: June 2022

Abstract
Folate status has been inversely associated with breast cancer risk. Because folate deficiency can cause DNA damage, such as uracil misincorporation, single strand breaks, and double strand breaks, genetic polymorphisms in base excision repair and double strand break repair genes may lead to variation in DNA repair proficiency and modify the effect of folate on breast cancer risk. We prospectively investigated the a priori hypothesized interaction between plasma folate levels and five nonsynonymous polymorphisms in the XRCC1, XRCC2, and XRCC3 genes on breast cancer risk in a nested case-control study within the Nurses' Health Study (712 case-control pairs). Suggestive evidence of interaction was seen for two of these polymorphisms. Compared with the reference group of non-carriers in the lowest quartile of plasma folate, the reduction in risk (66%) was statistically significant among XRCC1 194Trp carriers in the highest quartile (multivariate odds ratio, 0.34; 95% confidence interval, 0.16–0.72). The inverse association between XRCC1 194Trp and breast cancer risk was attenuated by lower plasma folate status. The inverse association between plasma folate level and breast cancer risk was stronger among 194Trp carriers (P, trend = 0.01) than non-carriers (P, trend = 0.09). We also observed that the positive association between the XRCC2 188His allele and breast cancer risk was only significant in women in the lowest plasma folate quartile (carriers versus non-carriers; multivariate odds ratio, 2.04; 95% confidence interval, 1.05–3.97), and this excess risk was abolished among those with higher plasma folate levels. Moreover, the inverse association between plasma folate level and breast cancer risk was stronger among XRCC2 188His carriers (P, trend = 0.004) than non-carriers (P, trend = 0.09). Although none of the statistical tests for interaction was significant, these data give some support for the hypothesis that genetic variations in DNA repair genes may modify the relation between plasma folate level and breast cancer risk.
Body Size and Composition and Colon Cancer Risk in Men
Authors: MacInnis Robert J. , English Dallas R. , Hopper John L. , Haydon Andrew M. , Gertig Dorota M. , Giles Graham G. 
Published: June 2022

Abstract
Background: Several studies of male colon cancer have found positive associations with body size and composition. It is uncertain whether this relationship is due to non-adipose mass, adipose mass, distribution of adipose mass such as central adiposity, or all three. Methods: In a prospective cohort study of men aged 27–75 at recruitment in 1990–1994, body measurements were taken by interviewers. Fat mass and fat-free mass (FFM) were estimated from bioelectrical impedance analysis. Waist circumference and waist-to-hips ratio (WHR) estimated central adiposity. Incident colon cancers were ascertained via the population cancer registry. Altogether, 16,556 men contributed 145,433 person-years and 153 colon cancers. Results: Rate ratios (RRs) comparing men in the fourth quartile with those in the first quartile were as follows: FFM 2.3 [95% confidence interval (CI) 1.4–3.7]; height 1.9 (95% CI 1.1–3.1); waist circumference 2.1 (95% CI 1.3–3.5); WHR 2.1 (95% CI 1.3–3.4); fat mass 1.8 (95% CI 1.1–3.0); and body mass index 1.7 (95% CI 1.1–2.8). When continuous measures of FFM and WHR were modeled together, the RR for FFM per 10 kg was 1.37 (95% CI 1.04–1.80) and the RR for WHR per 0.1 unit was 1.65 (95% CI 1.28–2.13). After adjustment for FFM and WHR, the RRs for fat mass and body mass index were no longer statistically significant. Conclusion: Male colon cancer appears to be related to body size and composition by two different pathways, via central adiposity and via non-adipose mass.
Alcohol, Wine, and Risk of Epithelial Ovarian Cancer
Authors: Webb Penelope M. , Purdie David M. , Bain Christopher J. , Green Adèle C. 
Published: June 2022

Abstract
Moderate alcohol intake can influence sex hormone levels and affect ovarian function as well as increasing breast cancer risk. This suggests that alcohol might also influence ovarian cancer risk. We have evaluated this among 696 Australian women with histologically confirmed epithelial ovarian cancer and 786 cancer-free control women, selected at random from the electoral roll. Sociodemographic information and a detailed reproductive history were collected in a face-to-face interview, and information about diet and alcohol consumption was obtained from a food frequency questionnaire. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Overall, 59% of women drank &lt;1 standard drink/week and only 5% of cases and 8% of controls drank an average of ≥2 standard drinks/day. Compared with nondrinkers, the OR for women who drank an average of ≥2 standard drinks/day was 0.49 (95% CI = 0.30–0.81). This effect did not vary for the different subtypes but was restricted to wine (OR = 0.56, 95% CI = 0.33–0.93 for ≥1 glass/day versus nondrinkers) with no effect for beer (OR = 1.26, 95% CI = 0.65–2.46) or sherry/spirits (OR = 1.07, 95% CI = 0.59–1.95). Combining our results with the six previous population-based studies gave a pooled OR of 0.72 (95% CI = 0.54–0.97) for the highest alcohol intake group versus nondrinkers. These data suggest that alcohol does not increase risk of ovarian cancer. In this Australian population, the inverse association with alcohol was due solely to wine consumption and so may be a consequence of antioxidants and/or phytoestrogens in wine rather than the alcohol itself.
Breast Cancer Risk Among Women Who Start Smoking as Teenagers
Authors: Gram Inger T. , Braaten Tonje , Terry Paul D. , Sasco Annie J. , Adami Hans-Olov , Lund Eiliv , Weiderpass Elisabete 
Published: June 2022

Abstract
Objective: To examine the effect of smoking on breast cancer risk in a large population-based cohort of women, many of whom started smoking as teenagers.
Methods: We followed 102,098 women, ages 30 to 50 years, completing a mailed questionnaire at recruitment to the Norwegian-Swedish Cohort Study in 1991/1992, through December 2000. We used Cox proportional hazard regression models to estimate relative risk (RR) of breast cancer associated with different measures of smoking initiation, duration, and intensity adjusting for confounding variables. We conducted analyses on the entire study population, among women who had smoked for at least 20 years, among nondrinkers, and separately for each country.
Results: Altogether, 1,240 women were diagnosed with incident, invasive breast cancer. Compared with never smokers, women who smoked for at least 20 years and who smoked 10 cigarettes or more daily had a RR of 1.34 (95% CI, 1.06-1.70). Likewise, those who initiated smoking prior to their first birth (1.27, 1.00-1.62), before menarche (1.39, 1.03-1.87), or before age 15 (1.48, 1.03-2.13) had an increased risk. In contrast, women who had smoked for at least 20 years, but started after their first birth, did not experience an increased breast cancer risk. The increased RR associated with smoking was observed among nondrinkers of alcohol, women with and without a family history of breast cancer, premenopausal and postmenopausal women, and in both countries.
Conclusion: Our results support the notion that women who start smoking as teenagers and continue to smoke for at least 20 years may increase their breast cancer risk.
Phytoestrogen Concentrations in Serum and Spot Urine as Biomarkers for Dietary Phytoestrogen Intake and Their Relation to Breast Cancer Risk in European Prospective Investigation of Cancer and Nutrition-Norfolk
Authors: Grace Philip B. , Taylor James I. , Low Yen-Ling , Luben Robert N. , Mulligan Angela A. , Botting Nigel P. , Dowsett Mitch , Welch Ailsa A. , Khaw Kay-Tee , Wareham Nick J. , Day Nick E. , Bingham Sheila A. 
Published: June 2022

Abstract
Subjects of this study consisted of 333 women (aged 45–75 years) drawn from a large United Kingdom prospective study of diet and cancer, the European Prospective Investigation of Cancer and Nutrition-Norfolk study. Using newly developed gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry methods incorporating triply 13C-labeled standards, seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in 114 spot urines and 97 available serum samples from women who later developed breast cancer. Results were compared with those from 219 urines and 187 serum samples from healthy controls matched by age and date of recruitment. Dietary levels were low, but even so, mean serum levels of phytoestrogens were up to 600 times greater than postmenopausal estradiol levels. Phytoestrogen concentrations in spot urine (adjusted for urinary creatinine) correlated strongly with that in serum, with Pearson correlation coefficients &gt; 0.8. There were significant relationships (P &lt; 0.02) between both urinary and serum concentrations of isoflavones across increasing tertiles of dietary intakes. Urinary enterodiol and enterolactone and serum enterolactone were significantly correlated with dietary fiber intake (r = 0.13–0.29). Exposure to all isoflavones was associated with increased breast cancer risk, significantly so for equol and daidzein. For a doubling of levels, odds ratios increased by 20–45% [log2 odds ratio = 1.34 (1.06–1.70; P = 0.013) for urine equol, 1.46 (1.05–2.02; P = 0.024) for serum equol, and 1.22 (1.01–1.48; P = 0.044) for serum daidzein]. These estimates of risk are similar to those established for estrogens and androgens in postmenopausal breast cancer but need confirmation in larger studies.
An Autosome-Wide Scan for Linkage Disequilibrium–Based Association in Sporadic Breast Cancer Cases in Eastern Finland: Three Candidate Regions Found
Authors: Hartikainen Jaana M. , Tuhkanen Hanna , Kataja Vesa , Dunning Alison M. , Antoniou Antonis , Smith Paula , Arffman Airi , Pirskanen Mia , Easton Douglas F. , Eskelinen Matti , Uusitupa Matti , Kosma Veli-Matti , Mannermaa Arto 
Published: June 2022

Abstract
Breast cancer is the most common of cancers among women in industrialized countries. Many of breast cancer risk factors are known, but the majority of the genetic background is still unknown. Linkage disequilibrium–based association is a powerful tool for mapping disease genes and is suitable for mapping complex traits in founder populations. We report the results of a two-stage, autosome-wide scan for LD with breast cancer. Our aim was to identify genetic risk factors for sporadic breast cancer in an eastern Finnish population. Our case-control set is from the province of northern Savo in the late-settlement area of eastern Finland. This population is relatively young and genetically homogeneous. We used 435 autosomal microsatellite markers spaced by an average of 10 cM in a set of 49 breast cancer cases and 50 controls. In the first-stage scan, we found 21 markers in LD with breast cancer (Ps = 0.003-0.046, Fisher's exact test). In the second-stage scan with markers flanking 21 positive loci, four significant markers were found (Ps = 0.013-0.046, Fisher's exact test). Haplotype analysis using global score method with two, three, or four markers also revealed four positive marker combinations (simulated P for global score = 0.003-0.021). Our results suggest breast cancer–associated regions on 3p26, 11q23, and 22q13.1 in an eastern Finnish population.
Factors Predicting Prostate Specific Antigen Testing among First-Degree Relatives of Prostate Cancer Patients
Authors: Vadaparampil Susan Thomas , Jacobsen Paul B. , Kash Kathryn , Watson Iryna S. , Saloup Raoul , Pow-Sang Julio 
Published: June 2022

AbstractFirst-degree relatives (FDRs) of prostate cancer patients are known to be at increased risk for the disease, yet relatively little is known about their screening behaviors. The current lack of consensus about the value of prostate cancer screening underscores the importance of examining why some men at increased risk participate in screening and others do not. In this study, variables from Protection Motivation Theory were used to identify predictors of prostate specific antigen (PSA) testing in this at-risk population. Toward this end, scales assessing perceived vulnerability, perceived severity, response efficacy, and self-efficacy for prostate cancer screening were administered to 82 unaffected male FDRs aged 40 and older. When recontacted approximately 14 months later, 50% of FDRs were found to have undergone PSA testing in the interim. Older age, prior prostate cancer screening, and a greater sense of personal efficacy about being able to undergo prostate cancer screening were found to be significant (P &lt; 0.05) predictors of subsequently undergoing PSA testing. These findings provide partial support for the predictive validity of Protection Motivation Theory variables and suggest the importance of considering efficacy beliefs in attempting to understand decision-making about PSA testing in at-risk individuals.
Selenium and Lung Cancer: A Quantitative Analysis of Heterogeneity in the Current Epidemiological Literature
Authors: Zhuo Hanjing , Smith Allan H. , Steinmaus Craig 
Published: June 2022

AbstractWhile numerous laboratory investigations have shown that selenium may have anticarcinogenic activity, the epidemiological data have been inconsistent. In this report, meta-analysis was used to quantitatively summarize the existing epidemiological evidence on selenium and lung cancer and identify sources of heterogeneity among studies. When all studies were combined, the summary relative risk (RR) for subjects with higher selenium exposures was 0.74 [95% confidence interval (CI) 0.57–0.97]. In subgroup analyses based on the average selenium level in the study population, the summary RR for areas where selenium levels were low was 0.72 (95% CI 0.45–1.16), while the RR for areas where selenium levels were higher was 0.86 (95% CI 0.61–1.22). In both studies in high selenium areas where RRs were markedly below 1.0, protective effects were only found when subjects in the lowest category of selenium exposure were used as referents. No clear protective effects were seen when highly exposed subjects were compared with those in the middle exposure categories. The summary RR was lower in studies assessing selenium exposure using toenails (RR 0.46, 95% CI 0.24–0.87) than in studies using serum selenium (RR 0.80, 95% CI 0.58–1.10) or studies assessing dietary intake (RR 1.00, 95% CI 0.77–1.30). Overall, these results suggest that selenium may have some protective effect against lung cancer in populations where average selenium levels are low. The evidence for these findings is greater in studies of toenail selenium than in studies involving other measures of exposure.
Assessment of Polymorphic Variants in the Melanocortin-1 Receptor Gene with Cutaneous Pigmentation Using an Evolutionary Approach
Authors: Kanetsky Peter A. , Ge Fan , Najarian Derek , Swoyer Jennifer , Panossian Saarene , Schuchter Lynn , Holmes Robin , Guerry DuPont , Rebbeck Timothy R. 
Published: June 2022

Abstract
The melanocortin-1 receptor gene (MC1R) encodes a membrane-bound receptor protein that is central to melanin synthesis. The coding region of MC1R is highly polymorphic and associations of variants with pigmentation phenotypes and risk for cutaneous neoplasms have been reported. We sought to determine the distribution and frequency of MC1R variants and their relationship to pigmentation characteristics in 179 Caucasian controls from the United States. One hundred thirty-five (75.4%) subjects carried one or more variants, and we determined that carriage of the previously designated “red hair color” (RHC) alleles, R151C, R160W, and D294H was strongly associated with fair pigmentation phenotypes including light hair and eye color, tendency to burn, decreased tendency to tan, and freckling. We used SIFT software to define MC1R protein positions that were predicted intolerant to amino acid substitutions; detected variants that corresponded to intolerant substitutions were D84E, R142H, R151C, I155T, R160W, and D294H. Carriage of one or more of these putative functionally important variants or the frameshift variant ins86A was significantly associated with fair pigmentation phenotypes. Analyses limited to carriage of ins86A and the three non-RHC alleles identified by SIFT were attenuated and no longer reached statistical significance. This is the first study to describe MC1R variants among control subjects from the U.S. Our results indicate that the frequency of variants is similar to that previously observed among non-U.S. Caucasians. Risk variants defined by either the published literature or by evolutionary criteria are strongly and significantly associated with all fair pigmentation phenotypes that were measured.