Multivitamin use and all-cause and cause-specific mortality in cancer survivors.

BACKGROUND: Despite no sufficient evidence on benefits and harms of multivitamin use, cancer survivors use multivitamins as a self-care strategy to improve or maintain health. We examined if multivitamin use was associated with mortality in cancer survivors. METHODS: 15,936 male and 7026 female cancer survivors in the NIH-AARP Diet and Health Study were included in the analysis. Types and frequency of multivitamin use at on average 4.6 years after cancer diagnosis were assessed. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models. RESULTS: Multivitamin use was not associated with lower all-cause mortality risk in all female (RR = 0.94, 95% CI:0.87-1.01 daily vs. no use) or male cancer survivors (RR = 0.96, 95% CI:0.91-1.00); however, a modest inverse association for CVD mortality was observed in female survivors of reproductive cancers (RR = 0.75, 95% CI:0.61-0.92) and male survivors of non-reproductive cancers (RR = 0.81, 95% CI:0.70-0.94). Multivitamin use was also associated with a lower risk of cancer-specific mortality in survivors of skin (RR = 0.65, 95% CI:0.48-0.88) and breast (RR = 0.79, 95% CI:0.65-0.95) cancer. DISCUSSION: Multivitamin use may provide a modest survival benefit to some cancer survivors. Cancer care providers should talk with cancer survivors about potential benefits and harms of multivitamin use.

Antioxidant and Antiproliferative Activities of Several Garlic Forms.

It is hypothesized that garlic, Allium sativum, might protect against oxidative stress that causes damage to cells and tissues leading to the development of various health conditions including cancer. However, it is not known whether garlic's potential anticancer benefits differ by form of garlic consumed. This study aimed to quantify and compare the in vitro antioxidant and antiproliferative activity of several garlic forms in water and alcohol extracts including fresh garlic, fresh garlic set aside, heated garlic, heated garlic set aside, garlic powder, black garlic, two commercially available garlic supplements. Antioxidant activity of different garlic forms were measured using three assays: DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay, superoxide assay, and hydroxyl assay. In vitro effects of garlic extracts were investigated against the most common lung cancer subtypes: H520, H1975, and A549 cell lines using the sulforhodamine B (SRB) assay. Among free radical scavenging assays, Garlicin®, a commercially available supplement, displayed high antioxidant activity in water and alcohol extracts (DPPH assay: 2.02 mg AAE (mg ascorbic acid equivalent)/g garlic and 3.53 mg AAE/g garlic, respectively; superoxide assay: 6.73 mg AAE/g garlic and 7.13 mg AAE/g garlic, respectively). In the hydroxyl assay, water extract of fresh garlic crushed and set aside for 10 min showed the highest antioxidant activity. Garlicin® alcohol extract and fresh garlic water extracts strongly inhibited the proliferation of H1975, A549 and H520 cells. Other forms of garlic including garlic powder and black garlic exhibited low antioxidant and antiproliferative activity. Our results demonstrate that the preparation and processing methods of garlic may lead to different antioxidant benefits.

Characteristics of Cancer Epidemiology Studies That Employ Metabolomics: A Scoping Review.

An increasing number of cancer epidemiology studies use metabolomics assays. This scoping review characterizes trends in the literature in terms of study design, population characteristics, and metabolomics approaches and identifies opportunities for future growth and improvement. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science: Core Collection databases and included research articles that used metabolomics to primarily study cancer, contained a minimum of 100 cases in each main analysis stratum, used an epidemiologic study design, and were published in English from 1998 to June 2021. A total of 2,048 articles were screened, of which 314 full texts were further assessed resulting in 77 included articles. The most well-studied cancers were colorectal (19.5%), prostate (19.5%), and breast (19.5%). Most studies used a nested case-control design to estimate associations between individual metabolites and cancer risk and a liquid chromatography-tandem mass spectrometry untargeted or semi-targeted approach to measure metabolites in blood. Studies were geographically diverse, including countries in Asia, Europe, and North America; 27.3% of studies reported on participant race, the majority reporting White participants. Most studies (70.2%) included fewer than 300 cancer cases in their main analysis. This scoping review identified key areas for improvement, including needs for standardized race and ethnicity reporting, more diverse study populations, and larger studies.

Association of ambient fine particulate matter exposure with gestational diabetes mellitus and blood glucose levels during pregnancy.

BACKGROUND: Previous studies have examined the associations between ambient fine particulate matter (PM2.5) exposure and gestational diabetes mellitus (GDM). However, limited studies explored the relationships between PM2.5 exposure and blood glucose levels during pregnancy, especially in highly polluted areas. OBJECTIVES: To examine the associations of prenatal ambient PM2.5 exposure with GDM and blood glucose levels, and to identify the sensitive exposure windows in a highly air-polluted area. METHODS: From July 2016 to October 2017, a birth cohort study was conducted in Beijing, China. Participants were interviewed in each trimester regarding demographics, lifestyle, living and working environment, and medical conditions. Participant's daily ambient PM2.5 levels from 3 m before last menstrual period (LMP) to the third trimester was estimated by a hybrid spatiotemporal model. Indoor air quality index was calculated based on environmental tobacco smoke, ventilation, cooking, painting, pesticide, and herbicide use. Distributed lag non-linear model was applied to explore the sensitive weeks of PM2.5 exposure. RESULTS: Of 165 pregnant women, 23 (13.94%) developed GDM. After adjusting for potential confounders, PM2.5 exposure during the 1st trimester was associated with higher odds of GDM (10 µg/m3 increase: OR = 1.89, 95% CI: 1.04-3.49). Each 10 µg/m3 increase in PM2.5 during the 2nd trimester was associated with 17.70% (2.21-33.20), 15.99% (2.96-29.01), 18.82% (4.11-33.52), and 17.10% (3.28-30.92) increase in 1-h, 2-h, Δ1h-fasting (1-h minus fasting), and Δ2h-fasting (2-h minus fasting) blood glucose levels, respectively. PM2.5 exposure at 24th-27th weeks after LMP was associated with increased GDM risk. We identified sensitive exposure windows of 21st-24th weeks for higher 1-h and 2-h blood glucose levels and of 20th-22nd weeks for increased Δ1h-fasting and Δ2h-fasting. CONCLUSIONS: Ambient PM2.5 exposure during the second trimester was associated with higher odds of GDM and higher blood glucose levels. Avoiding exposure to high air pollution levels during the sensitive windows might prevent women from developing GDM.

A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary tract cancer.

Bile acids (BAs), major regulators of the gut microbiota, may play an important role in hepatobiliary cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and liver or biliary tract cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, we designed 1:1 matched, nested, case-control studies of primary liver cancer (n = 201 cases), fatal liver disease (n = 261 cases), and primary biliary tract cancer (n = 138 cases). Using baseline serum collected ≤30 years before diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography-tandem mass spectrometry. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable conditional logistic regression models, adjusted for age, education, diabetes status, smoking, alcohol intake, and body mass index. We accounted for multiple comparisons using a false discovery rate (FDR) correction. Comparing the highest to the lowest quartile, seven BAs were positively associated with liver cancer risk, including taurocholic acid (TCA) (OR, 5.62; 95% CI, 2.74-11.52; Q trend < 0.0001), taurochenodeoxycholic acid (TCDCA) (OR, 4.77; 95% CI, 2.26-10.08; Q trend < 0.0001), and glycocholic acid (GCA) OR, 5.30; 95% CI, 2.41-11.66; Q trend < 0.0001), and 11 were positively associated with fatal liver disease risk, including TCDCA (OR, 9.65; 95% CI, 4.41-21.14; Q trend < 0.0001), TCA (OR, 7.45; 95% CI, 3.70-14.97; Q trend < 0.0001), and GCA (OR, 6.98; 95% CI, 3.32-14.68; Q trend < 0.0001). For biliary tract cancer, associations were generally >1 but not significant after FDR correction. Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between BA metabolism and liver cancer or death from liver disease.

Correlation of Vertical Dentoalveolar Heights with Palatal Plane Inclination in Adults with Different Vertical Facial Patterns / Corrélation des hauteurs dento-alvéolaires verticales avec l'inclinaison du plan palatin chez les adultes présentant différentes typologies faciales verticales

Introduction: Various studies showed inconsistent and different results regarding the correlation between open bites and palate planes whether normal or abnormal. This study had for objective to investigate the correlation between dentoalveolar heights and palatal plane inclination in different vertical facial patterns. Materials and Methods: 120 lateral cephalometric radiographs (60 females and 60 males) were selected from the archives of the Faculty of Dentistry, Beirut Arab University. The sample consisted of three equal groups: hypodivergent (SN/MP<27°), normodivergent (SN/MP=27°-37°) and hyperdivergent (SN/MP>37°). The radiographs were digitally traced and cephalometric skeletal and dentoalveolar variables were measured. Statistical analysis was carried out with significance level at p<0.05. Results: The palatal plane inclination showed statistically significant difference between hyperdivergent and both hypodivergent and normodivergent subjects with no statistically significant difference between hypodivergent and normodivergent subjects. A statistically significant difference in the upper anterior dentoalveolar height (UADAH) was found between hypodivergent and both hyperdivergent and normodivergent subjects. No statistically significant difference was found in the other dentoalveolar heights between the different vertical patterns. A negative moderate correlation was only observed between the palatal plane angle and UADAH in the hyperdivergent group. Multiregression analysis showed that the greatest contribution to overbite pooled across all groups other than the skeletal pattern was attributed to UADAH. Conclusion: UADAH seems to influence the overbite depth compared to other dentoalveolar heights. It is possible that UADAH acts as a compensatory factor for palatal plane inclination in hyperdivergent subjects.

Introduction: Diverses études ont montré des résultats incohérents et différents concernant la corrélation entre les béances et les plans du palais, qu'ils soient normaux ou anormaux. Cette étude avait pour objectif d'analyser la corrélation entre les hauteurs dento-alvéolaires et l'inclinaison du plan palatin dans différentes typologies faciales verticales. Matériels et méthodes: Au total, 120 radiographies céphalométriques latérales (60 femmes et 60 hommes) ont été sélectionnées dans les archives de la Faculté de médecine dentaire de l'Université Arabe de Beyrouth. L'échantillon était composé de trois groupes égaux : hypodivergent (SN/PM < 27°), normodivergent (SN/PM = 27° - 37°) et hyperdivergent (SN/PM > 37°). Les radiographies ont été tracées numériquement et les variables squelettiques et dento-alvéolaires céphalométriques ont été mesurées. L'analyse statistique a été réalisée avec un seuil de signification à p < 0,05. Résultats: L'inclinaison du plan palatin a montré une différence statistiquement significative entre les sujets hyperdivergents et les sujets hypodivergents et normodivergents, sans différence statistiquement significative entre les sujets hypodivergents et normodivergents. Une différence statistiquement significative dans la hauteur dento-alvéolaire antérieure supérieure (HDAAS) a été trouvée entre les sujets hypodivergents et les sujets hyperdivergents et normodivergents. Aucune différence statistiquement significative n'a été trouvée dans les autres hauteurs dento-alvéolaires entre les différents modèles verticaux. Une corrélation négative modérée n'a été observée qu'entre l'angle du plan palatin et la HDAAS dans le groupe hyperdivergent. L'analyse multirégression a montré que la plus grande contribution à la supraclusion regroupée dans tous les groupes autres que le schéma squelettique était attribuée à la HDAAS. Conclusion: La HDAAS semble influencer la profondeur de supraclusion par rapport aux autres hauteurs dento-alvéolaires. Il est possible que celle-ci agisse comme un facteur compensateur de l'inclinaison du plan palatin chez les sujets hyperdivergents.

Reproducibility, Temporal Variability, and Concordance of Serum and Fecal Bile Acids and Short Chain Fatty Acids in a Population-Based Study.

BACKGROUND: Bile acid (BA) and short chain fatty acid (SCFA) production is affected by diet and microbial metabolism. These metabolites may play important roles in human carcinogenesis. METHODS: We used a fully quantitative targeted LC-MS/MS system to measure serum and fecal BA and SCFA concentrations in 136 Costa Rican adults at study baseline and 6-months. We randomly selected 50 participants and measured their baseline samples in duplicate. Our objective was to evaluate: Technical reproducibility; 6-month temporal variability; and concordance between sample type collected from the same individual at approximately the same time. RESULTS: Technical reproducibility was excellent, with intraclass correlation coefficients (ICC) ≥0.83 for all BAs except serum tauroursodeoxycholic acid (ICC = 0.72) and fecal glycolithocholic acid (ICC = 0.66) and ICCs ≥0.81 for all SCFAs except serum 2-methylbutyric acid (ICC = 0.56) and serum isobutyric acid (ICC = 0.64). Temporal variability ICCs were generally low, but several BAs (i.e., deoxycholic, glycoursodeoxycholic, lithocholic, taurocholic, and tauroursodeoxycholic acid) and SCFAs (i.e., 2-methylbutyric, butyric, propionic, and valeric acid) had 6-month ICCs ≥0.44. The highest degree of concordance was observed for secondary and tertiary BAs. CONCLUSIONS: Serum and fecal BAs and SCFAs were reproducibly measured. However, 6-month ICCs were generally low, indicating that serial biospecimen collections would increase statistical power in etiologic studies. The low concordance for most serum and fecal metabolites suggests that consideration should be paid to treating these as proxies. IMPACT: Our findings will inform the design and interpretation of future human studies on associations of BAs, SCFAs, and potentially other microbial metabolites, with disease risk.

Periodontal Disease and Breast Cancer Risk: Results from the Nurses' Health Study.

BACKGROUND: While periodontal disease has been linked to increased cancer risk, studies regarding an association with breast cancer are limited. METHODS: We examined the relationship between self-reported diagnosis of periodontal bone loss and incidence of breast cancer in a large, prospective cohort study, the Nurses' Health Study (1998-2014). We calculated HRs using Cox proportional hazards modeling, adjusting for risk factors common to both periodontal disease and breast cancer. RESULTS: During 1,023,647 person-years of follow-up, 5,110 of breast cancer cases were reported. We observed no association between periodontal disease and overall breast cancer risk (HR, 1.02; 95% confidence interval: 0.94-1.10); the association was not modified by smoking status, or other breast cancer risk factors or by breast tumor subtypes. CONCLUSIONS: We did not observe any association between periodontal disease and breast cancer risk. IMPACT: Given inconsistent findings in the literature, further research with standardized clinical measures of periodontitis is warranted.

Changes in arachidonic acid (AA)- and linoleic acid (LA)-derived hydroxy metabolites and their interplay with inflammatory biomarkers in response to drastic changes in air pollution exposure.

BACKGROUND: Untargeted metabolomics analyses have indicated that fatty acids and their hydroxy derivatives may be important metabolites in the mechanism through which air pollution potentiates diseases. This study aimed to use targeted analysis to investigate how metabolites in arachidonic acid (AA) and linoleic acid (LA) pathways respond to short-term changes in air pollution exposure. We further explored how they might interact with markers of antioxidant enzymes and systemic inflammation. METHODS: This study included a subset of participants (n = 53) from the Beijing Olympics Air Pollution (BoaP) study in which blood samples were collected before, during, and after the Beijing Olympics. Hydroxy fatty acids were measured by liquid chromatography/mass spectrometry (LC/MS). Native total fatty acids were measured as fatty acid methyl esters (FAMEs) using gas chromatography. A set of chemokines were measured by ELISA-based chemiluminescent assay and antioxidant enzyme activities were analyzed by kinetic enzyme assays. Changes in levels of metabolites over the three time points were examined using linear mixed-effects models, adjusting for age, sex, body mass index (BMI), and smoking status. Pearson correlation and repeated measures correlation coefficients were calculated to explore the relationships of metabolites with levels of serum chemokines and antioxidant enzymes. RESULTS: 12-hydroxyeicosatetraenoic acid (12-HETE) decreased by 50.5% (95% CI: -66.5, -34.5; p < 0.0001) when air pollution dropped during the Olympics and increased by 119.4% (95% CI: 36.4, 202.3; p < 0.0001) when air pollution returned to high levels after the Olympics. In contrast, 13-hydroxyoctadecadienoic acid (13-HODE) elevated significantly (p = 0.023) during the Olympics and decreased nonsignificantly after the games (p = 0.104). Interleukin 8 (IL-8) correlated with 12-HETE (r = 0.399, BH-adjusted p = 0.004) and 13-HODE (r = 0.342, BH-adjusted p = 0.014) over the three points; it presented a positive and moderate correlation with 12-HETE during the Olympics (r = 0.583, BH-adjusted p = 0.002) and with 13-HODE before the Olympics (r = 0.543, BH-adjusted p = 0.008). CONCLUSION: AA- and LA-derived hydroxy metabolites are associated with air pollution and might interact with systemic inflammation in response to air pollution exposure.

Types of garlic and their anticancer and antioxidant activity: a review of the epidemiologic and experimental evidence.

Garlic, an Allium vegetable, contains rich flavonoids organosulfur compounds (OSCs) that have potent anticancer properties. The aim of the review is to provide an overview of the different types of garlic, their active compounds, and the potential anticancer benefits with a focus on antioxidant activity. Animal and cell line studies have provided convincing evidence that garlic and its organosulfur compounds inhibit carcinogenesis through a number of events including induction of apoptosis, inhibiting cellular proliferation, scavenging radical oxygen species (ROS), increasing the activities of enzymes such as glutathione S-transferase, and reducing tumor size. Epidemiological studies showed compelling evidence that garlic consumption is associated with decreased risk of colorectal cancer, but inconsistent evidence for stomach, breast, and prostate cancers. Studies also suggest that the presence and potency of garlic OSCs varies with respect to the preparation and form of garlic. Further epidemiological studies with information on garlic form consumed or preparation methods and molecular studies regarding its antioxidant mechanisms, such as increasing enzymatic and nonenzymatic antioxidants levels, are warranted.

Responses of serum chemokines to dramatic changes of air pollution levels, a panel study.

Background: Despite the in vitro and in vivo evidence, studies are limited in evaluating whether chemokines are potential inflammatory mediators in response to air pollution exposure in humans. Methods: We conducted a panel study coinciding with the Beijing Olympics, when temporary air pollution controls were implemented. We measured a suite of serum chemokines among healthy adults before, during and after the Olympics, respectively. Linear mixed-effect models were used to evaluate changes in chemokine levels over the three time periods. Results: In response to the 50% drop in air pollution levels during the games, levels of RANTES, MCP-2, and TARC decreased by 25.8%, 20.9% and 35.3%, respectively (p < 0.001) from pre-Olympics, and then increased by 45.8%, 34.9% and 61.5%, respectively (p < 0.001) after the games when air pollution levels went up again. Similar patterns were observed in subgroup analyses by sex, age, smoking and body mass index. GRO-α and IL-8 decreased significantly during the games (22.5% and 30.4%), and increased non-significantly after the games. Eotaxin-1 only increased significantly from during- to post-games. Conclusions: The strongest associations with air pollution levels were observed among RANTES, TARC and MCP-2. Those chemokines may play important roles in the air pollution-induced inflammatory pathway.

How do glutathione antioxidant enzymes and total antioxidant status respond to air pollution exposure?

This study aims to investigate how antioxidant enzyme activity and overall antioxidant capacity respond to short-term changes in exposure to air pollution. 201 participants were recruited before- and followed up during- and after- the 2008 Beijing Olympics. Serum levels of antioxidant enzymes including glutathione S-transferases (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and total antioxidant status (TAS) were measured. We used linear mixed-effects models to compare changes in antioxidant enzymes across the three periods after adjusting for potential confounding factors. Among all participants, glutathione peroxidase (GPx) levels decreased by 12.0% when air pollution dropped by 50-60% during the Olympics and increased by 6.5% when air pollution levels rose after the Olympics. The magnitude of increase among males, smokers, and older individuals was relatively smaller compared to females, nonsmokers, and younger individuals. Among all participants, total antioxidant status (TAS) significantly decreased by 6.23% during the games and continued to decrease by 4.41% after the games. However, among females, nonsmokers, and younger participants, there was an increase in TAS response to the elevated air pollution levels. Our study observed strong responses in GPx and TAS levels to the short-term decrease and increase of air pollution levels and responses varied among subgroups.

Standardized cancer incidence disparities in Upper Manhattan New York City neighborhoods: the role of race/ethnicity, socioeconomic status, and known risk factors.

We examined the effects of race/ethnicity and neighborhood, a proxy of socioeconomic status, on cancer incidence in New York City neighborhoods: East Harlem (EH), Central Harlem (CH), and Upper East Side (UES). In this ecological study, Community Health Survey data (2002-2006) and New York State Cancer Registry incidence data (2007-2011) were stratified by sex, age, race/ethnicity, and neighborhood. Logistic regression models were fitted to each cancer incidence rate with race/ethnicity, neighborhood, and Community Health Survey-derived risk factors as predictor variables. Neighborhood was significantly associated with all cancers and 14 out of 25 major cancers. EH and CH residence conferred a higher risk of all cancers compared with UES (OR=1.34, 95% CI 1.07-1.68; and OR=1.39, 95% CI 1.12-1.72, respectively). The prevalence of diabetes and tobacco smoking were the largest contributors toward high cancer rates. Despite juxtaposition and similar proximity to medical centers, cancer incidence disparities persist among EH, CH, and UES neighborhoods. Targeted, neighborhood-specific outreach may aid in reducing cancer incidence rates.