bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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 <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

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

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 > 0.8. There were significant relationships (P < 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

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

First-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 < 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

While 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

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.
Results of a Phase I Multiple-Dose Clinical Study of Ursodeoxycholic Acid
Authors: Hess Lisa M. , Krutzsch Mary F. , Guillen Jose , Chow H-H. Sherry , Einspahr Janine , Batta A.K. , Salen Gerald , Reid Mary E. , Earnest David L. , Alberts David S.
Published: June 2022

Background: The hydrophilic bile acid, ursodeoxycholic acid (UDCA), may indirectly protect against colon carcinogenesis by decreasing the overall proportion of the more hydrophobic bile acids, such as deoxycholic acid (DCA), in aqueous phase stool. In the AOM rat model, treatment with UDCA resulted in a significant decrease in adenoma formation and colorectal cancer. It was hypothesized that there is a dose-response relationship between treatment with the more hydrophilic bile acid, UDCA, and a reduction in the proportion of the more hydrophobic bile acid, DCA, in the aqueous stool phase, suggesting the potential of UDCA as a chemopreventive agent. Methods: Eighteen participants were randomized to 300, 600, or 900 mg/day UDCA for 21 days in this multiple-dose, double-blinded study. Seventy-two-hour stool samples were collected pretreatment and on days 18–20 of UDCA treatment for bile acid measurements. Pharmacokinetics were performed and blood bile acids were measured at days 1 and 21 of UDCA treatment. Results: There were no serious adverse events associated with UDCA treatment. There was a dose-response increase in the posttreatment to baseline ratio of UDCA to DCA from the 300 mg/day to the 600 mg/day group, but not between the 600 and the 900 mg/day groups, in both aqueous and solid phase stool. This posttreatment increase was statistically significant in aqueous phase stool for the 300 and 600 mg/day treatment groups (P = 0.038 and P = 0.014, respectively), but was only marginally significant in the 900 mg/day treatment group (P = 0.057). Following the first dose administration, a dose-dependent increase in plasma ursodeoxycholic concentrations was observed in fasting subjects; however, when these levels were measured postprandially following 3 weeks of treatment, the areas under the plasma concentration-time profile (AUC) were not statistically different and remained relatively unchanged over time. Conclusions: UDCA treatment did not decrease the quantity of DCA in fecal water or solids; however, it did decrease the proportion of DCA in fecal water and solids in relation to UDCA. Thus, 3 weeks of UDCA treatment resulted in an overall increase in hydrophilicity of bile acids in the aqueous phase stool, with a peak effect observed with a daily dose of 600 mg/day. Much larger studies are needed to determine the effect of ursodeoxycholic administration on deoxycholic concentration, overall hydrophilicity of stool bile acids, and the long-term effects on intermediate biomarkers of cellular damage.
Association of Cyclin D1 Genotype with Breast Cancer Risk and Survival
Authors: Shu Xiao Ou , Moore Derek B. , Cai Qiuyin , Cheng Jiarong , Wen Wanqing , Pierce Larry , Cai Hui , Gao Yu-Tang , Zheng Wei
Published: June 2022

Cyclin D1 (CCND1) is a key cell cycle regulatory protein that governs cell cycle progression from the G1 to S phase. A common polymorphism (A870G) in exon 4 of the CCND1 gene produces an alternate transcript (transcript-b) that preferentially encodes a protein with enhanced cell transformation activity and possible prolonged half-life. We evaluated the association of CCND1 A870G polymorphism with breast cancer risk and survival in 1,130 breast cancer cases and 1,196 controls who participated in the Shanghai Breast Cancer Study. Approximately 81% of cases and 79% of controls carried the A allele at A870G of the CCND1 gene [odds ratio, 1.1; 95% confidence interval (95% CI), 0.9-1.4]. As lightly stronger but nonsignificant association was found for the A allele among younger women (odds ratio, 1.3; 95% CI, 0.9-1.8). However, this polymorphism seems to modify the effect of hormonal exposures on postmenopausal breast cancer, as the positive associations of postmenopausal breast cancer with body mass index (Pfor interaction = 0.02) and waist-to-hip ratios (P for interaction < 0.03; all Ps are two sided) were only observed among women who carry the A allele at A870G of the CCND1 gene. Following up with this cohort of patients for an average of 4.84 years, we found that the CCND1 A870G polymorphism was inversely associated with overall and disease-free survival, particularly among women with late stage or estrogen/progesterone receptor-negative breast cancer. The adjusted hazard ratios for disease-free survival associated with GA and AA genotypes were 0.94 (95% CI, 0.49-1.82) and 0.41 (95% CI, 0.19-0.91) for tumor-node-metastasis stage III to IV breast cancer, and 0.35 (95% CI, 0.15-0.80) and 0.32 (95% CI, 0.13-0.79) for estrogen/progesterone receptor-negative breast cancer. This study suggests that CCND1 A870G polymorphism may modify the postmenopausal breast cancer risk associated with hormonal exposure and predict survival after breast cancer diagnosis.
Helicobacter pylori and Malignant Lymphoma in Spain
Authors: de Sanjose Silvia , Dickie Andrew , Alvaro Tomas , Romagosa Vicens , Garcia Villanueva Mercedes , Domingo-Domenech Eva , Fernandez de Sevilla Alberto , El-Omar Emad
Published: June 2022

Helicobacter pylori has been associated with gastric adenocarcinoma and gastric lymphoma. We report on the systematic evaluation of serologic detection of H. pylori in a lymphoma case-control study. Methods: Cases (N = 536) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in four centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (N = 603) were hospitalized patients frequency-matched to the cases by 5-year age group, sex, and study center. Severe immunocompromised patients were excluded as controls. Patients underwent a personal interview and blood sampling. H. pylori infection was evaluated by the presence of IgG antibodies using the Premier enzyme immunoassay kit (Meridian Diagnostics Inc., Cincinnati, OH). Logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for lymphoma categories. Results: Anti-H. pylori antibodies were detected in 68.5% of the cases and 71.3% of the controls (P = 0.29) H. pylori was associated with a 3-fold excess risk of splenic marginal B-cell lymphoma (OR = 3.97, 95% CI = 0.92-17.16). H. pylori was not associated with an overall increased risk of extranodal lymphomas (OR = 0.73, 95% CI = 0.44-1.22) but when specific sites were explored, the four mucosa-associated lymphoid tissue and the six diffuse large B-cell lymphomas primary localized in the stomach were all H. pylori seropositive. Conclusion: Persistent infection with H. pylori may be implicated in the development of lymphomas of the gastric mucosa and of the spleen. These results could have clinical implications in the management of splenic marginal zone lymphomas.
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-Methylguanine-DNA Methyltransferase Gene: Epigenetic Silencing and Prognostic Value in Head and Neck Squamous Cell Carcinoma
Authors: Zuo Chunlai , Ai Lingbao , Ratliff Pam , Suen James Y. , Hanna Ehab , Brent Thomas P. , Fan Chun-Yang
Published: June 2022

Background: Alkylating N-nitroso compounds can interact directly with DNA, forming O6-alkylguanine, a DNA adduct proved to be mutagenic and carcinogenic if not sufficiently repaired. A specific DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), can remove the alkyl group from the O6-position of the guanine, thereby preventing its mutagenic and carcinogenic effects. Inactivation of the MGMT gene in association with promoter hypermethylation results in persistence of O6-alkylguanine in DNA, leading to G:C to A:T transition mutation and these G:C to A:T transition mutations can inactivate p53 tumor suppressor gene or activate ras proto-oncogene. Methods: We analyzed MGMT promoter hypermethylation and protein expression patterns in 94 cases of primary head and neck squamous cell carcinoma (HNSCC) by methylation-specific PCR (MSP) and immunohistochemical staining. The results were then correlated with clinical follow-up data. Results: MGMT promoter hypermethylation was present in 17 of 94 patients (18.1%) and apparent loss of protein expression was seen in 19 of 93 HNSCC patients (20.4%). The presence of MGMT promoter hypermethylation was significantly correlated with loss of MGMT protein expression in HNSCC. Both MGMT promoter hypermethylation and loss of protein expression were significantly correlated to increased tumor recurrences and decreased patient survival, independent of other risk factors, such as tumor site, tumor size, nodal status, age, and chemoradiation therapy. Conclusions: MGMT promoter hypermethylation and apparent loss of protein expression are reliable and independent prognostic factors in HNSCC. The above study may also provide guideline or basis for applying alkylating antitumor agents to patients with HNSCC that display MGMT promoter hypermethylation and/or loss of MGMT protein expression.
Effects of Cruciferous Vegetable Consumption on Urinary Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Singapore Chinese
Authors: Hecht Stephen S. , Carmella Steven G. , Kenney Patrick M.J. , Low Siew-Hong , Arakawa Kazuko , Yu Mimi C.
Published: June 2022

Vegetable consumption, including cruciferous vegetables, is protective against lung cancer, but the mechanisms are poorly understood. The purpose of this study was to investigate the effects of cruciferous vegetable consumption on the metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers. The study was carried out in Singapore Chinese, whose mean daily intake of cruciferous vegetables is three times greater than that of people in the United States. Eighty-four smokers provided urine samples and were interviewed about dietary habits using a structured questionnaire, which included questions on consumption of nine commonly consumed cruciferous vegetables. Samples of these vegetables obtained in Singapore markets at three different times of year were analyzed for glucosinolates. Urine was analyzed for metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs). Glucobrassicins, which release indole-3-carbinols on chewing, were the major glucosinolates in seven of the nine cruciferous vegetables, accounting for 70.0% to 93.2% of all glucosinolates in these vegetables. There was a significant correlation (P = 0.01) between increased consumption of glucobrassicins and decreased levels of NNAL in urine after adjustment for number of cigarettes smoked per day; similar trends were observed for NNAL-Glucs (P = 0.08) and NNAL plus NNAL-Glucs (P = 0.03). These results are consistent with those of previous studies, which demonstrate that indole-3-carbinol decreases levels of urinary NNAL probably by inducing hepatic metabolism of NNK. The results are discussed with respect to the known chemopreventive activity of indole-3-carbinol against lung tumorigenesis by NNK in mice and the effects of isothiocyanates, which are also formed on consumption of cruciferous vegetables, on NNK metabolism. The results of this study demonstrate the complexities in assessing effects of cruciferous vegetables on carcinogen metabolism.
Multi-Cancer Early Detection Tests: Current Progress and Future Perspectives
Authors: Loomans-Kropp Holli A. , Umar Asad , Minasian Lori M. , Pinsky Paul F.
Published: June 2022

Advances in cancer screening and early detection methodologies may lead to the detection of precancerous lesions or early-stage cancer. The development of blood-based multi-cancer early detection (MCED) tests may aid in this challenge. Furthermore, MCED tests have the potential to address early detection gaps for cancers with and without screening modalities and lessen cancer disparities, but many unknowns remain. In this issue, Clarke and colleagues describe stage- and cancer-specific incidence and survival, derived from Surveillance, Epidemiology and End Results Program Data, stratified by race/ethnicity and sex. The investigators discuss the potential to identify earlier-stage cancers (stage shift) that could improve overall patient outcomes. In a simulation model, the authors found fewer cancer-related deaths when cancers were down-staged at the time of diagnosis. In this commentary, we discuss some unanswered questions in using MCED tests for screening, as well as what stage shifting may actually mean for patient outcomes.

See related article by Clarke et al., p. 521
Spontaneous Resolution of Macular Edema with Abnormal Vessel Crossing near the Central Macula by Congenital Retinal Macrovessel
Authors: Okamoto Rina , Nishida Kentaro , Hara Chikako , Wakabayashi Taku , Sakaguchi Hirokazu , Nishida Kohji
Published: June 2022

We present a case of a congenital retinal macrovessel (CRM) with spontaneous resolution of cystoid macular edema. A 39-year-old woman with sudden decreased vision in her right eye was referred to our clinic and found to have a CRM with macular edema. Her visual acuity was 20/25. A week later, the macular edema disappeared without any treatment, and her visual acuity was 20/15. We performed optical coherence tomography angiography and fluorescein angiography (FA), which revealed no obstruction of retinal flow but a slight disturbance of retinal flow near the central fovea on FA. We encountered a case of spontaneous resolution of macular edema with abnormal vessel crossing near the central macula by a CRM, and multimodal imaging was useful for investigating the pathology of the disease.
Impact of Social Media Exposure on Risk Perceptions, Mental Health Outcomes, and Preventive Behaviors during the COVID-19 Pandemic in Saudi Arabia
Authors: Alrasheed Meshael , Alrasheed Salman , Alqahtani Amani Salem
Published: June 2022

Introduction: Social media has played a key role in mediating the communication of information during the COVID-19 pandemic. The way information is shared through social media shapes people’s risk perceptions, which in turn affects their mental health and behaviors. This study aimed to assess social media’s impact on the public’s risk perceptions, mental health, and preventive behaviors during the peak of the COVID-19 pandemic. Methods: A Web-based survey was developed to assess social media exposure, risk perceptions, mental health, and COVID-19-related preventive behaviors among adults in Saudi Arabia. Multivariate logistic regression analysis was used to identify the association between social media exposure and key measurements. Results: A total of 1,500 individuals participated in the study; of those, 93.2% of participants reported using social media for COVID-19-related information. Twitter (68.3%) followed by Snapchat (25.1%) were the most used platforms. About 44.4% of participants were highly exposed to social media. High social media exposure was significantly associated with higher risks of anxiety (OR = 1.56, 95% CI: 1.19–2.05) and depression (OR = 1.47, 95% CI: 1.01–2.81) and higher levels of COVID-19 risk perception (OR = 1.43, 95% CI: 1.08–1.89). However, social media has no significant impact on the adoption of preventive behaviors. Discussion/Conclusion: Our results were consistent with the other international studies that were conducted during the COVID-19 pandemic. The anticipated future increase in social media use urges the need for longitudinal studies to investigate the psychological and behavioral effects of social media during emerging pandemics.
Correlação espacial da covid-19 com leitos de unidades de terapia intensiva no Paraná
Authors: Covre Eduardo Rocha , Pereira Natan David , Oliveira Natan Nascimento de , Charlo Patrícia Bossolani , Oliveira Magda Lúcia Félix de , Oliveira Rosana Rosseto de , Carreira Lígia , Facchini Luiz Augusto , Vissoci João Ricardo Nickenig , Salci Maria Aparecida
Published: June 2022

OBJETIVO Analisar a correlação espacial entre os casos confirmados de covid-19 com os leitos de unidades de terapia intensiva exclusivos para a doença nos municípios do Paraná. MÉTODO Trata-se de um estudo epidemiológico, do tipo ecológico que utilizou dados do Informe Epidemiológico fornecido pela Secretaria de Estado da Saúde do Paraná sobre os casos confirmados de covid-19, no período de 12 de março de 2020 a 18 de janeiro de 2021. A quantidade de leitos de terapia intensiva exclusivos para covid-19 de cada município paranaense foi obtida pelo Cadastro Nacional de Estabelecimentos de Saúde disponibilizado online pelo Departamento de Informática do Sistema Único de Saúde. A variável leito de terapia intensiva foi analisada pelo Índice Bivariado de Moran (local e global). Para a identificação de áreas críticas e de transição utilizou-se o LISA Map. Para avaliar a correlação espacial foi utilizado o Índice Bivariado de Moran, considerando o nível de significância de 5%. RESULTADOS No período analisado foram confirmados 499.777 casos de covid-19 no Paraná e identificados 1.029 leitos de terapia intensiva exclusivos para a doença entre os municípios do estado. Foi identificado autocorrelação espacial positiva entre os casos confirmados de covid-19 (0,404–p ≤ 0,001) com os leitos de terapia intensiva exclusivos para a doença (0,085–p ≤ 0,001) e disparidades entre as regiões do Paraná. CONCLUSÃO A análise espacial permitiu confirmar a relação entre os casos confirmados de covid-19 e a distribuição de leitos de terapia intensiva exclusivos para a doença no Paraná e possibilitou identificar áreas prioritárias de atenção no estado, relacionadas à disseminação e controle da doença.
“I Wouldn’t Want to Be a Gender Expert:” Gender Experts in Peace Mediation
Authors: Sapiano Jenna , Heathcote Gina , True Jacqui , Aggestam Karin
Published: June 2022

Peace mediation is a professional practice that is increasingly reliant on thematic technical experts, including gender experts. The strategy of including gender expertise in peace mediation reflects the Women, Peace and Security agenda and the call to include dedicated gender expertise in all peacemaking efforts. Based on interviews with peace mediation practitioners, the article analyzes the role of gender experts in peace mediation. We argue that there is a tension between the art of mediation and the art of gender expertise that reflects the gendered power dynamics of peace mediation. We conclude that the strategy of appointing gender experts to peace mediation teams will not “dismantle the master’s house.” However, we acknowledge that without a gender expert very little will be accomplished on this issue. For peace mediation to address the gendered foundations of conflict we argue for the development of an alternate feminist peace mediation practice.
Astragalus durandianus (sect. Trachycercis) as an Iranian endemic species: emended description, distribution, and conservation
Authors: GHAHREMANINEJAD FARROKH , JOHARCHI MOHAMMAD REZA , MEMARIANI FARSHID
Published: June 2022

An emended description of Iranian endemic Astragalus durandianus is provided with illustrations and extra information on several morphological characters not indicated in the protologue, including corolla characteristics, the habit size, peduncle length, bigger fruit size, black hairs on the fruits and several other differences. Based on field observations, a brief description of the habitat and data on ecology and biogeography of the species are provided. The conservation status of all species of Astragalus section Trachycercis in the Iranian plateau is evaluated.
Worship as Social Creativity: Social Identity and the Form of Psalm 79
Authors: Smith H. Clay
Published: June 2022

The form of Ps. 79 is often assessed as disoriented and disorienting. This study examines how the disoriented form of Ps. 79 creatively bolsters communal identity in the face of affliction primarily on the basis of the psalmist’s contention that God remains faithful to the covenant community. When one assesses the form of the psalm through the framework of social identity theory, three social creativity strategies become apparent, which facilitate a positive reassessment of social identity following crisis, namely, (1) the psalmist redefines the valence of the community’s state of affliction as an attribute that should inspire God’s compassionate response, (2) the psalmist engages in downward social comparison by villainizing adversarial nations for their arrogance and iniquity, and (3) the psalmist embraces the community’s commitment to worship. Consequently, the psalm’s medium and message enable recovery from its life setting.
To what extent is the Moses story modelled on other biblical stories?
Authors: Schellekens J. Jona
Published: June 2022

This essay reviews the evidence for the Moses story having been modelled on four other biblical stories. It is well known that the Moses story shares elements with the stories of Jeroboam, Elijah and Jacob. Few, however, have noted that the Moses story also appears to share elements with the story of King Joash of Judah. This essay presents an overview of the many elements which the Moses story shares with these four stories. It shows that most episodes in the life of Moses appear to have a parallel in the stories of these other biblical figures. After listing the many similarities, it presents a review of the evidence for direct dependence of the Moses story on the stories of the four other biblical figures.
Potential therapeutic effects of Ivermectin in COVID-19
Authors: Barati Nastaran , Motavallihaghi Seyedmousa , Nikfar Banafsheh , Chaichian Shahla , Momtazi-Borojeni Amir Abbas
Published: June 2022

COVID-19 is a critical pandemic that affected communities around the world, and there is currently no specific drug treatment for it. The virus enters the human cells via spikes and induces cytokine production and finally arrests the cell cycle. Ivermectin shows therapeutic potential for treating COVID-19 infection based on in vitro studies. Docking studies have shown a strong affinity between Ivermectin and some virulence factors of COVID-19. Notably, clinical evidence has demonstrated that Ivermectin with usual doses is effective by both the prophylactic and therapeutic approaches in all phases of the disease. Ivermectin inhibits both the adhesion and replication of the virus. Local therapy of the lung with Ivermectin or combination therapy may get better results and decrease the dose of the drug.
KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target
Authors: Cheminant Morgane , Lhermitte Ludovic , Bruneau Julie , Sicard Hélène , Bonnafous Cécile , Touzart Aurore , Bourbon Estelle , Ortonne Nicolas , Genestier Laurent , Gaulard Philippe , Palmic Patricia , Suarez Felipe , Frenzel Laurent , Naveau Louise , Bazarbachi Ali , Dussiot Mickaël , Waast Laetitia , Avettand-Fenoel Véronique , Brouzes Chantal , Pique Claudine , Lepelletier Yves , Asnafi Vahid , Marçais Ambroise , Hermine Olivier
Published: June 2022

Adult T-cell leukemia (ATL) is a lymphoid neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1), which encodes the transcriptional activator Tax, which participates in the immortalization of infected T cells. ATL is classified into 4 subtypes: smoldering, chronic, acute, and lymphoma. We determined whether natural killer receptors (NKRs) were expressed in ATL. NKR expression (KIR2DL1/2DS1, KIR2DL2/2DL3/2DS2, KIR3DL2, NKG2A, NKG2C, and NKp46) was assessed in a discovery cohort of 21 ATL, and KIR3DL2 was then assessed in 71 patients with ATL. KIR3DL2 was the only NKR among those studied frequently expressed by acute-type vs lymphoma- and chronic/smoldering-type ATL (36 of 40, 4 of 16, and 1 of 15, respectively; P = .001), although acute- and lymphoma-type ATL had similar mutation profiles by targeted exome sequencing. The correlation of KIR3DL2 expression with promoter demethylation was determined by microarray-based DNA methylation profiling. To explore the role of HTLV-1, KIR3DL2 and TAX messenger RNA (mRNA) expression levels were assessed by PrimeFlow RNA in primary ATL and in CD4+ T cells infected with HTLV-1 in vitro. TAX mRNA and KIR3DL2 protein expressions were correlated on ATL cells. HTLV-1 infection triggered KIR3DL2 by CD4+ cells but Tax alone did not induce KIR3DL2 expression. Ex vivo, autologous, antibody-dependent cell cytotoxicity using lacutamab, a first-in-class anti-KIR3DL2 humanized antibody, selectively killed KIR3DL2+ primary ATL cells ex vivo. To conclude, KIR3DL2 expression is associated with acute-type ATL. Transcription of KIR3DL2 may be triggered by HTLV-1 infection and correlates with hypomethylation of the promoter. The benefit of targeting KIR3DL2 with lacutamab is being further explored in a randomized phase 2 study in peripheral T-cell lymphoma, including ATL (registered on https://clinicaltrials.gov as #NCT04984837).
The association between oral health and nutritional status in older adults: a cross-sectional study
Authors: Khoury Claudine , Samot Johan , Helmer Catherine , Rosa Rafael Weber , Georget Aurore , Dartigues Jean-François , Arrivé Elise
Published: June 2022

Objectives

This work aimed to describe the nutritional status of French older adults (age ≥ 90 years) and studied the association between oral health and nutritional status.

Methods

A cross-sectional study was carried out in 2014 among the participants of a cohort on cerebral and functional aging in France at their 25-year follow up (the PAQUID cohort). Nutritional status (Mini Nutritional Assessment [MNA]) and oral health status (number of decayed, missing, and filled teeth [DMFT], number of posterior occluding pairs, xerostomia [Xerostomia Inventory], and prosthetic rehabilitation) were recorded at the participants’ living places by two dentists. Univariate and multivariate logistic regressions were used to explore the association between oral health and nutritional status, with adjustments for potential confounders. Odds ratios (OR) were estimated with their 95% confidence interval (CI).

Results

87 participants were included in the analyses: 74.7% were females and the mean age was 94.1 years (± 3.0). Malnutrition or risk of malnutrition (MNA < 24) was present in 23 participants (26.4%), with only one having malnutrition. The mean DMFT score was 26.5 (± 5.3). The mean number of posterior occluding pairs was 1.5 (± 2.3). Twenty-one participants had xerostomia (24.1%). Only 8.1% of the participants had all their teeth or adequate dentures; 47.1% had inadequate dentures, while 44.8% had no dentures despite tooth loss. After adjustment, xerostomia (OR = 8.79; 95% CI = 2.38–39.10; p = 0.002) was found to be associated with malnutrition or risk of malnutrition.

Conclusion

Being at risk of malnutrition was common among people ≥ 90 years old and was associated with xerostomia. NCT04065828.