Hypertension and risk of endometrial cancer: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: The incidence rates of endometrial cancer (EC) are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for EC. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of EC remains unclear. In this study we evaluated hypertension as an independent risk factor for EC and whether this association is modified by other established risk factors. METHODS: We included 15,631 EC cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between hypertension and EC and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of EC (OR=1.14, 95% CI:1.09-1.19). There was significant heterogeneity by study design (Phet<0.01), with a stronger magnitude of association observed among case-control vs. cohort studies. Stronger associations were also noted for pre-/peri-menopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with EC risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for EC.

Sleep duration and mortality among breast cancer survivors in the Western New York Exposures and Breast Cancer (WEB) Study.

PURPOSE: There is increasing evidence that sleep duration may affect breast cancer survival through effects on circadian function, influencing disease progression. However, further investigation of this association is needed. METHODS: In a population-based, prospective cohort study of women from the Western New York Exposures and Breast Cancer Study, we examined mortality outcomes with invasive breast cancer identified using the National Death Index. Cox proportion hazards ratios with 95% confidence intervals were used to estimate risk of all-cause (AC) and breast cancer-specific (BC) mortality associated with self-reported usual sleep duration with adjustment for age, race/ethnicity, years of education, body mass index (BMI), menopausal status, pack-years of smoking, tumor stage, and estrogen-receptor (ER) status. We further examined associations within strata of BMI, tumor stage, menopausal status, and ER status. RESULTS: A sample of 817 patients with breast cancer were followed for a median of 18.7 years, during which 339 deaths were reported, including 132 breast cancer-specific deaths. Those who reported shorter or longer sleep tended to have a slightly higher BMI, to be less proportionately non-Hispanic White, to report a previous history of benign breast disease, and to have consumed more alcohol during their lifetime. We found no significant associations between sleep duration and AC or BC mortality, including within stratified analyses. CONCLUSION: Sleep duration was not associated with either AC or BC mortality including within strata of BMI, tumor stage, menopausal status, or ER status.

Alcohol Consumption and the Diversity of the Oral Microbiome in Postmenopausal Women.

BACKGROUND: Alcohol reduces neutrophil function and decreases salivary flow, which could affect the composition of the oral microbiome. OBJECTIVE: We hypothesized that the α- and ß-diversity of the oral microbiome and the relative abundance of bacterial taxa would differ by frequency and type of alcohol consumption. METHODS: We used a food frequency questionnaire to assess the frequency of consumption of beer, wine, and liquor (drinks/week) in a sample of 1179 postmenopausal women in the Osteoporosis and Periodontal Disease Study. Women were categorized as nondrinkers, drinking <1 drink/wk, ≥1 to <7 drinks/wk, or ≥7 drinks/wk for total alcohol consumption and for beer, wine, and liquor consumption. The composition and diversity of the oral microbiome was assessed from subgingival plaque samples using 16S ribosomal RNA amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) was used to examine ß-diversity (between-sample diversity) in the microbiome between alcohol consumption categories. Analysis of covariance was used to examine the mean α-diversity (within-sample diversity), assessed by the Shannon index (species evenness), Chao1 index (species richness), and observed operational taxonomic unit (OTU) count and the mean relative abundance of 245 bacterial taxa across alcohol consumption categories. RESULTS: Over half of the participants (67%) consumed alcohol, with 14% reporting ≥1 drink/d. The ß-diversity across categories of total alcohol consumption, but not categories of alcohol type, was statistically significantly different (P for PERMANOVA = 0.016). Mean α-diversity measures were statistically significantly higher (P < 0.05) in the highest category of total alcohol and wine consumption compared to nondrinkers; no significant associations were found for beer or liquor consumption. The relative abundance of 1 OTU, Selenomonassp._oral_taxon_133, was significantly lower in the highest level of total alcohol consumption compared to nondrinkers after adjustment for multiple comparisons. CONCLUSIONS: Alcohol consumption was associated with the diversity and composition of the subgingival microbiome.

Accelerated epigenetic age, inflammation, and gene expression in lung: comparisons of smokers and vapers with non-smokers.

BACKGROUND: Cigarette smoking and aging are the main risk factors for pulmonary diseases, including cancer. Epigenetic aging may explain the relationship between smoking, electronic cigarette vaping, and pulmonary health. No study has examined smoking and vaping-related epigenetic aging in relation to lung biomarkers. METHODS: Lung epigenetic aging measured by DNA methylation (mAge) and its acceleration (mAA) was assessed in young (age 21-30) electronic cigarette vapers (EC, n = 14, including 3 never-smoking EC), smokers (SM, n = 16), and non-EC/non-SM (NS, n = 39). We investigated relationships of mAge estimates with chronological age (Horvath-mAge), lifespan/mortality (Grim-mAge), telomere length (TL-mAge), smoking/EC history, urinary biomarkers, lung cytokines, and transcriptome. RESULTS: Compared to NS, EC and SM had significantly older Grim-mAge, shorter TL-mAge, significantly accelerated Grim-mAge and decelerated TL-mAge. Among SM, Grim-mAA was associated with nicotine intake and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). For EC, Horvath-mAA was significantly correlated with puffs per day. Overall, cytokines (IL-1ß, IL-6, and IL-8) and 759 transcripts (651 unique genes) were significantly associated with Grim-mAA. Grim-mAA-associated genes were highly enriched in immune-related pathways and genes that play a role in the morphology and structures of cells/tissues. CONCLUSIONS: Faster lung mAge for SM is consistent with prior studies of blood. Faster lung mAge for EC compared to NS indicates possible adverse pulmonary effects of EC on biological aging. Our findings support further research, particularly on epigenetic markers, on effects of smoking and vaping on pulmonary health. Given that most EC are former smokers, further study is needed to understand unique effects of electronic cigarettes on biological aging.

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.

Untargeted Metabolomics and Body Mass in Adolescents: A Cross-Sectional and Longitudinal Analysis.

Obesity in children and adolescents has increased globally. Increased body mass index (BMI) during adolescence carries significant long-term adverse health outcomes, including chronic diseases such as cardiovascular disease, stroke, diabetes, and cancer. Little is known about the metabolic consequences of changes in BMI in adolescents outside of typical clinical parameters. Here, we used untargeted metabolomics to assess changing BMI in male adolescents. Untargeted metabolomic profiling was performed on urine samples from 360 adolescents using UPLC-QTOF-MS. The study includes a baseline of 235 subjects in a discovery set and 125 subjects in a validation set. Of them, a follow-up of 81 subjects (1 year later) as a replication set was studied. Linear regression analysis models were used to estimate the associations of metabolic features with BMI z-score in the discovery and validation sets, after adjusting for age, race, and total energy intake (kcal) at false-discovery-rate correction (FDR) ≤ 0.1. We identified 221 and 16 significant metabolic features in the discovery and in the validation set, respectively. The metabolites associated with BMI z-score in validation sets are glycylproline, citrulline, 4-vinylsyringol, 3'-sialyllactose, estrone sulfate, carnosine, formiminoglutamic acid, 4-hydroxyproline, hydroxyprolyl-asparagine, 2-hexenoylcarnitine, L-glutamine, inosine, N-(2-Hydroxyphenyl) acetamide glucuronide, and galactosylhydroxylysine. Of those 16 features, 9 significant metabolic features were associated with a positive change in BMI in the replication set 1 year later. Histidine and arginine metabolism were the most affected metabolic pathways. Our findings suggest that obesity and its metabolic outcomes in the urine metabolome of children are linked to altered amino acids, lipid, and carbohydrate metabolism. These identified metabolites may serve as biomarkers and aid in the investigation of obesity's underlying pathological mechanisms. Whether these features are associated with the development of obesity, or a consequence of changing BMI, requires further study.

Disparities in insecurity, social support, and family relationships in association with poor mental health among US adults during the COVID-19 pandemic.

The COVID-19 pandemic has had a significant impact on mental health. Identifying risk factors and susceptible subgroups will guide efforts to address mental health concerns during the pandemic and long-term management and monitoring after the pandemic. We aimed to examine associations of insecurity (concerns about food, health insurance, and/or money), social support, and change in family relationships with poor mental health and to explore disparities in these associations. An online survey was collected from 3952 US adults between May and August 2020. Symptoms of anxiety, depression, stress, and trauma-related disorders were assessed by the Generalized Anxiety Disorder 7-item scale, the Patient Health Questionnaire-9, the Perceived Stress Scale-4, and the Primary Care Post-Traumatic Stress Disorder Screen, respectively. Social support was measured by the Oslo Social Support Scale. Logistic regression was used and stratified analyses by age, race/ethnicity, and sex were performed. We found a higher prevalence of poor mental health among those who were younger, female, with lower socioeconomic status, and racial/ethnic minorities. Participants who were worried about money, health insurance, or food had higher odds of symptoms of anxiety (OR = 3.74, 95% CI: 3.06-4.56), depression (OR = 3.20, 95% CI: 2.67-3.84), stress (OR = 3.08, 95% CI: 2.67-3.57), and trauma-related disorders (OR = 2.93, 95% CI: 2.42-3.55) compared to those who were not. Compared to poor social support, moderate and strong social support was associated with lower odds of all four symptoms. Participants who had changes in relationships with parents, children, or significant others had worse mental health. Our findings identified groups at higher risk for poor mental health, which offers insights for implementing targeted interventions.

A Pilot Cross-Sectional Study of Immunological and Microbiome Profiling Reveals Distinct Inflammatory Profiles for Smokers, Electronic Cigarette Users, and Never-Smokers.

Smokers (SM) have increased lung immune cell counts and inflammatory gene expression compared to electronic cigarette (EC) users and never-smokers (NS). The objective of this study is to further assess associations for SM and EC lung microbiomes with immune cell subtypes and inflammatory gene expression in samples obtained by bronchoscopy and bronchoalveolar lavage (n = 28). RNASeq with the CIBERSORT computational algorithm were used to determine immune cell subtypes, along with inflammatory gene expression and microbiome metatranscriptomics. Macrophage subtypes revealed a two-fold increase in M0 (undifferentiated) macrophages for SM and EC users relative to NS, with a concordant decrease in M2 (anti-inflammatory) macrophages. There were 68, 19, and 1 significantly differentially expressed inflammatory genes (DEG) between SM/NS, SM/EC users, and EC users/NS, respectively. CSF-1 and GATA3 expression correlated positively and inversely with M0 and M2 macrophages, respectively. Correlation profiling for DEG showed distinct lung profiles for each participant group. There were three bacteria genera-DEG correlations and three bacteria genera-macrophage subtype correlations. In this pilot study, SM and EC use were associated with an increase in undifferentiated M0 macrophages, but SM differed from EC users and NS for inflammatory gene expression. The data support the hypothesis that SM and EC have toxic lung effects influencing inflammatory responses, but this may not be via changes in the microbiome.

Alcohol Consumption and Mental Health during the COVID-19 Pandemic.

AIMS: To examine the association between alcohol consumption and mental health during the COVID-19 pandemic. METHODS: An anonymous online survey was distributed among US adults during May-August 2020 through social networks and ResearchMatch. We collected information on demographic, lifestyles and mental health symptoms including anxiety, depression, stress and post-traumatic stress disorder. Logistic regression models were used to examine the cross-sectional association between alcohol consumption and mental health symptoms. We also examined effect modification by race, age, gender, social support, financial insecurity and quarantine status. RESULTS: The analytical sample consists of 3623 adults. Stable drinking habits and regular drinking behaviors were found to co-exist with better mental health status. Participants who increased their alcohol use had higher odds of developing mental health disorders than those who maintained their pre-pandemic drinking habits. Additionally, participants who engaged in binge drinking during the pandemic had higher odds of depression and stress than those who did not. The associations regarding increased drinking and binge drinking in relation to adverse mental health outcomes were stronger among females, racial minorities, and individuals with financial concerns, poor social support and restricted quarantine status than their counterparts. CONCLUSIONS: During the early stage of the COVID-19 pandemic, increased alcohol use and binge drinking are cross-sectionally associated with higher odds of mental health disorders, which highlighted the need for targeted intervention to address the mental health needs of individuals who have engaged in these behaviors, especially among females, minorities, those with insecurities or with restricted quarantine status.

Dietary Fats and All-cause and Breast Cancer-specific Mortality among Women with Breast Cancer: The Western New York Exposures and Breast Cancer Study.

BACKGROUND: Study results of prediagnostic dietary fat intake and breast cancer mortality have been inconclusive. While dietary fat subtypes [saturated (SFA), polyunsaturated (PUFA), and monounsaturated (MUFA) fatty acids] may have different biological effects, there is little evidence regarding the association of dietary fat and fat subtype intake with mortality after breast cancer diagnosis. METHODS: Women with incident, pathologically confirmed invasive breast cancer and complete dietary data (n = 793) were followed in a population-based study, the Western New York Exposures and Breast Cancer study. Usual intake before diagnosis of total fat and subtypes were estimated from a food frequency questionnaire completed at baseline. HRs and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality were estimated with Cox proportional hazards models. Interactions by menopausal status, estrogen receptor (ER) status, and tumor stage were examined. RESULTS: Median follow-up time was 18.75 years; 327 (41.2%) participants had died. Compared with lower intake, greater intake of total fat (HR, 1.05; 95% CI, 0.65-1.70), SFA (1.31; 0.82-2.10), MUFA (0.99; 0.61-1.60), and PUFA (0.99; 0.56-1.75) was not associated with breast cancer-specific mortality. There was also no association with all-cause mortality. Results did not vary by menopausal status, ER status, or tumor stage. CONCLUSIONS: Prediagnostic intake of dietary fat and fat subtypes was not associated with either all-cause or breast cancer mortality in a population-based cohort of breast cancer survivors. IMPACT: Understanding factors affecting survival among women diagnosed with breast cancer is critically important. Dietary fat intake prior to diagnosis may not impact that survival.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Risk prediction models for endometrial cancer: development and validation in an international consortium.

BACKGROUND: Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. METHODS: We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses' Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. RESULTS: Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O] = 1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O = 1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O = 0.55, 95% CI = 0.51 to 0.59). CONCLUSIONS: Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.

Lung mitochondrial DNA copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers.

BACKGROUND: Mitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, and is linked to nuclear DNA methylation and gene expression. Increased mtCN in the blood is associated with smoking and respiratory disease, but has received little attention for target organ effects for smoking or electronic cigarette (EC) use. METHODS: Bronchoscopy biospecimens from healthy EC users, smokers (SM), and never-smokers (NS) were assessed for associations of mtCN with mtDNA point mutations, immune responses, nuclear DNA methylation and gene expression using linear regression. Ingenuity pathway analysis was used for enriched pathways. GEO and TCGA respiratory disease datasets were used to explore the involvement of mtCN-associated signatures. FINDINGS: mtCN was higher in SM than NS, but EC was not statistically different from either. Overall there was a negative association of mtCN with a point mutation in the D-loop but no difference within groups. Positive associations of mtCN with IL-2 and IL-4 were found in EC only. mtCN was significantly associated with 71,487 CpGs and 321 transcripts. 263 CpGs were correlated with nearby transcripts for genes enriched in the immune system. EC-specific mtCN-associated-CpGs and genes were differentially expressed in respiratory diseases compared to controls, including genes involved in cellular movement, inflammation, metabolism, and airway hyperresponsiveness. INTERPRETATION: Smoking may elicit a lung toxic effect through mtCN. While the impact of EC is less clear, EC-specific associations of mtCN with nuclear biomarkers suggest exposure may not be harmless. Further research is needed to understand the role of smoking and EC-related mtCN on lung disease risks. FUNDING: The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds.

Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking.

The microbiome has increasingly been linked to cancer. Little is known about the lung and oral cavity microbiomes in smokers, and even less for electronic cigarette (EC) users, compared with never-smokers. In a cross-sectional study (n = 28) of smokers, EC users, and never-smokers, bronchoalveolar lavage and saliva samples underwent metatranscriptome profiling to examine associations with lung and oral microbiomes. Pairwise comparisons assessed differentially abundant bacteria species. Total bacterial load was similar between groups, with no differences in bacterial diversity across lung microbiomes. In lungs, 44 bacteria species differed significantly (FDR < 0.1) between smokers/never-smokers, with most decreased in smokers. Twelve species differed between smokers/EC users, all decreased in smokers of which Neisseria sp. KEM232 and Curvibacter sp. AEP1-3 were observed. Among the top five decreased species in both comparisons, Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae were observed. In the oral microbiome, 152 species were differentially abundant for smokers/never-smokers, and 17 between smokers/electronic cigarette users, but only 21 species were differentially abundant in both the lung and oral cavity. EC use is not associated with changes in the lung microbiome compared with never-smokers, indicating EC toxicity does not affect microbiota. Statistically different bacteria in smokers compared with EC users and never-smokers were almost all decreased, potentially due to toxic effects of cigarette smoke. The low numbers of overlapping oral and lung microbes suggest that the oral microbiome is not a surrogate for analyzing smoking-related effects in the lung. PREVENTION RELEVANCE: The microbiome affects cancer and other disease risk. The effects of e-cig usage on the lung microbiome are essentially unknown. Given the importance of lung microbiome dysbiosis populated by oral species which have been observed to drive lung cancer progression, it is important to study effects of e-cig use on microbiome.

Differences in somatic TP53 mutation type in breast tumors by race and receptor status.

PURPOSE: Somatic driver mutations in TP53 are associated with triple-negative breast cancer (TNBC) and poorer outcomes. Breast cancers in women of African ancestry (AA) are more likely to be TNBC and have somatic TP53 mutations than cancers in non-Hispanic White (NHW) women. Missense driver mutations in TP53 have varied functional impact including loss-of-function (LOF) or gain-of-function (GOF) activity, and dominant negative (DNE) effects. We aimed to determine if there were differences in somatic TP53 mutation types by patient ancestry or TNBC status. METHODS: We identified breast cancer datasets with somatic TP53 mutation data, ancestry, age, and hormone receptor status. Mutations were classified for functional impact using published data and type of mutation. We assessed differences using Fisher's exact test. RESULTS: From 96 breast cancer studies, we identified 2964 women with somatic TP53 mutations: 715 (24.1%) Asian, 258 (8.7%) AA, 1931 (65.2%) NHW, and 60 (2%) Latina. The distribution of TP53 mutation type was similar by ancestry. However, 35.8% of tumors from NHW individuals had GOF mutations compared to 29% from AA individuals (p = 0.04). Mutations with DNE activity were positively associated with TNBC (OR 1.37, p = 0.03) and estrogen receptor (ER) negative status (OR 1.38; p = 0.005). CONCLUSIONS: Somatic TP53 mutation types did not differ by ancestry overall, but GOF mutations were more common in NHW women than AA women. ER-negative and TNBC tumors are less likely to have DNE+ TP53 mutations which could reflect biological processes. Larger cohorts and functional studies are needed to further elucidate these findings.

Dietary carbohydrate intake is associated with the subgingival plaque oral microbiome abundance and diversity in a cohort of postmenopausal women.

Limited research exists on carbohydrate intake and oral microbiome diversity and composition assessed with next-generation sequencing. We aimed to better understand the association between habitual carbohydrate intake and the oral microbiome, as the oral microbiome has been associated with caries, periodontal disease, and systemic diseases. We investigated if total carbohydrates, starch, monosaccharides, disaccharides, fiber, or glycemic load (GL) were associated with the diversity and composition of oral bacteria in subgingival plaque samples of 1204 post-menopausal women. Carbohydrate intake and GL were assessed from a food frequency questionnaire, and adjusted for energy intake. The V3-V4 region of the 16S rRNA gene from subgingival plaque samples were sequenced to identify the relative abundance of microbiome compositional data expressed as operational taxonomic units (OTUs). The abundance of OTUs were centered log(2)-ratio transformed to account for the compositional data structure. Associations between carbohydrate/GL intake and microbiome alpha-diversity measures were examined using linear regression. PERMANOVA analyses were conducted to examine microbiome beta-diversity measures across quartiles of carbohydrate/GL intake. Associations between intake of carbohydrates and GL and the abundance of the 245 identified OTUs were examined by using linear regression. Total carbohydrates, GL, starch, lactose, and sucrose intake were inversely associated with alpha-diversity measures. Beta-diversity across quartiles of total carbohydrates, fiber, GL, sucrose, and galactose, were all statistically significant (p for PERMANOVA p < 0.05). Positive associations were observed between total carbohydrates, GL, sucrose and Streptococcus mutans; GL and both Sphingomonas HOT 006 and Scardovia wiggsiae; and sucrose and Streptococcus lactarius. A negative association was observed between lactose and Aggregatibacter segnis, and between sucrose and both TM7_[G-1] HOT 346 and Leptotrichia HOT 223. Intake of total carbohydrate, GL, and sucrose were inversely associated with subgingival bacteria alpha-diversity, the microbial beta-diversity varied by their intake, and they were associated with the relative abundance of specific OTUs. Higher intake of sucrose, or high GL foods, may influence poor oral health outcomes (and perhaps systemic health outcomes) in older women via their influence on the oral microbiome.

Perinatal factors, female breast cancer, and associated risk factors in Puerto Rico: evidence from the Atabey epidemiology of breast cancer study.

PURPOSE: There is increasing evidence that exposures in utero and in infancy impact breast cancer risk. No previous studies have evaluated these associations among women in Puerto Rico. METHODS: In a population-based case-control study of breast cancer epidemiology in the San Juan metropolitan area in Puerto Rico, we examined the association of early life factors with breast cancer risk and breast cancer risk factors. Both cases (n = 315) and controls (n = 348) completed interviewer-administered questionnaires, including self-reported birth country, birthweight, and history of having been breastfed. Comparisons of characteristics of those with and without the early life factors were made with t-tests or chi-squared tests; associations between early life factors and breast cancer risk were estimated with unconditional logistic regression adjusting for age, education, body mass index (BMI), age at menarche, parity, and menopausal status. RESULTS: Women who had been breastfed tended to have higher adult body mass index (BMI), higher education, and lower parity (p < 0.05). Higher birthweight was associated with higher adult BMI and lower educational attainment (p < 0.05). Those born outside of Puerto Rico or the US were more likely to have higher educational attainment and earlier age at menarche than those born within Puerto Rico or the US (p < 0.05). We found no significant associations between any of the early life factors and breast cancer risk. CONCLUSION: We did not find evidence of an association of early life factors with breast cancer risk among women in Puerto Rico.

Sun Exposure Is Associated with Reduced Breast Cancer Risk among Women Living in the Caribbean: The Atabey Study in Puerto Rico.

BACKGROUND: Though inconsistent, there is evidence that sun exposure is associated with reduced breast cancer risk. Previous studies have been conducted in geographical regions with seasonal variation in UV radiation, including periods of low to no exposure, and among participants mostly of European descent. Puerto Rico has no significant seasonal fluctuation, with continuous exposure to very high UV radiation. METHODS: We conducted a population-based case-control study of breast cancer among women in metropolitan San Juan, Puerto Rico, examining a cumulative sun exposure index (SEI) based on a comparison of reflectance of sun-exposed and non-exposed skin. A chromameter was used to measure skin reflectance and estimate the difference between constitutive (unexposed) and facultative (exposed) skin pigmentation in 307 cases and 328 controls. Breast cancer risk factors were ascertained with interviewer-administered questionnaires. OR and 95% confidence intervals (CI) were estimated with unconditional logistic regression. RESULTS: Adjusted breast cancer odds were lower for the highest tertile of the SEI (ORadj = 0.47; 95% CI, 0.29-0.74). Results were similar within strata of estrogen receptor status. In analyses stratified by constitutive skin pigmentation, among participants with darker skin color, breast cancer risk was lower with more sun exposure (ORadj = 0.33; 95% CI, 0.16-0.70). CONCLUSIONS: We found lower risk of breast cancer associated with greater sun exposure in a population living with high, continuous sun exposure. This beneficial finding should be placed in the context of other effects of sun exposure. IMPACT: Sun exposure is a modifiable factor that may contribute, directly or indirectly, to lower breast cancer risk.

Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative.

Research findings remain inconsistent whether caffeine consumption is associated with invasive breast cancer. We aimed to examine the association between caffeine intake from coffee and tea and incident invasive breast cancer among postmenopausal women. We included 79 871 participants in the Women's Health Initiative Observational Study in the current analysis. Incident invasive breast cancers were identified through September 30, 2015. Caffeine intake (mg/day) from caffeinated and decaffeinated coffee and tea was estimated based on self-reported frequency (cups/day) and average caffeine amount in each beverage. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore whether associations of caffeine intake from coffee and tea with invasive breast cancer were different by age, race and ethnicity, smoking status, body mass index, history of hormone therapy use, alcohol intake and subtypes of breast cancer. During a median follow-up of 16.0 years, 4719 incident invasive breast cancers were identified. No significant association was found between caffeine intake from coffee and tea and invasive breast cancer incidence after adjusting for demographic, lifestyle and reproductive factors: HRs (95% CIs) for increasing quartiles of caffeine intake compared to the lowest were 1.03 (0.94, 1.12), 1.04 (0.95, 1.13) and 1.03 (0.94, 1.13), respectively (P-for-trend = .54). No significant associations of coffee and tea intake (cups/day) with overall breast cancer risk were found. Our findings are consistent with others showing no clear association of caffeine consumption with invasive breast cancer among postmenopausal women.