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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.

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.

PURPOSE Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed < 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred forty-two (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.

Background Ovarian cancer is the fifth most common cause of cancer death among women in the US, yet few modifiable risk factors have been established. Diets high in glycemic index (GI) and glycemic load (GL) have been linked to several cancers, but epidemiologic studies of ovarian cancer have yielded inconsistent results. Objective In this study, we aimed to examine associations between GI or GL and ovarian cancer. Methods We used prospective data from the Prostate, Lung, Colorectal, and Ovarian cohort. GI and GL were calculated from validated FFQs. Participants were women who were aged 60 to 74 y, did not have a history of cancer, and had both ovaries. Cox proportional hazard models were used to calculate HRs and 95% CIs for risk of ovarian cancer associated with quartiles of GI and GL. Analyses were performed separately for those who completed the dietary questionnaire at baseline (DQX) or later in the study (DHQ). Results From the DQX sample set, 181 cases were identified among 24,633 women with median follow-up of 12.1 y; there were 211 cases among 42,410 women in the DHQ set, with median follow-up of 8.9 y. After adjusting for age at dietary questionnaire completion, year of randomization, year of questionnaire, study center, and oral contraceptive use, the risk of ovarian cancer decreased by 43% (HR: 0.57; 95% CI: 0.37, 0.88) among those in the highest compared with those in the lowest quartile of GL (DQX). Those in the highest compared with those in the lowest quartile of GI (DHQ), had a 38% lower risk (HR: 0.62; 95% CI: 0.42, 1.00). Conclusions We observed lower risk of ovarian cancer associated with higher GI and GL. Results should be interpreted with caution as they may have been influenced by limitations including lack of variability in dietary intake. Additional studies are needed to better understand what is driving these associations.

Background: There is growing evidence of an association between sugar-sweetened beverages (SSB) and increased risk of mortality in various populations. However, SSB influence on mortality among patients with breast cancer is unknown. Methods: We assessed the relationship between sugar-sweetened soda and both all-cause and breast cancer mortality among women with incident, invasive breast cancer from the Western New York Exposures and Breast Cancer Study. Breast cancer cases were followed for a median of 18.7 years, with ascertainment of vital status via the National Death Index. Frequency of sugar-sweetened soda consumption was determined via dietary recall using a food frequency questionnaire. Cox proportional hazards, adjusting for relevant variables, were used to estimate HRs and 95% confidence intervals (CI). Results: Of the 927 breast cancer cases, 386 (54.7%) had died by the end of follow-up. Compared with never/rarely sugar-sweetened soda drinkers, consumption at ≥5 times per week was associated with increased risk of both total (HR = 1.62; 95% CI, 1.16–2.26; Ptrend < 0.01) and breast cancer mortality (HR = 1.85; 95% CI, 1.16–2.94; Ptrend < 0.01). Risk of mortality was similarly increased among ER-positive, but not ER-negative patients; among women with body mass index above the median, but not below the median; and among premenopausal, but not postmenopausal women for total mortality only. Conclusions: Reported higher frequency of sugar-sweetened soda intake was associated with increased risks of both total and breast cancer mortality among patients with breast cancer. Impact: These results support existing guidelines on reducing consumption of SSB, including for women with a diagnosis of breast cancer.

Background: Nicotine-containing electronic cigarette (e-cig) use has become widespread. However, understanding the biological impact of e-cigs compared with smoking on the lung is needed. There are major gaps in knowledge for chronic effects and for an etiology to recent acute lung toxicity leading to death among vapers. Methods: We conducted bronchoscopies in a cross-sectional study of 73 subjects (42 never-smokers, 15 e-cig users, and 16 smokers). Using bronchoalveolar lavage and brushings, we examined lung inflammation by cell counts, cytokines, genome-wide gene expression, and DNA methylation. Results: There were statistically significant differences among never-smokers, e-cig users, and smokers for inflammatory cell counts and cytokines (FDR q < 0.1). The e-cig users had values intermediate between smokers and never-smokers, with levels for most of the biomarkers more similar to never-smokers. For differential gene expression and DNA methylation, e-cig users also more like never-smokers; many of these genes corresponded to smoking-related pathways, including those for xenobiotic metabolism, aryl hydrocarbon receptor signaling, and oxidative stress. Differentially methylated genes were correlated with changes in gene expression, providing evidence for biological effects of the methylation associations. Conclusions: These data indicate that e-cigs are associated with less toxicity than cigarettes for smoking-related pathways. What is unknown may be unique effects for e-cigs not measured herein, and a comparison of smokers completely switching to e-cigs compared with former smokers. Clinical trials for smokers switching to e-cigs who undergo serial bronchoscopy and larger cross-sectional studies of former smokers with and without e-cig use, and for e-cigs who relapse back to smoking, are needed. Impact: These data can be used for product regulation and for informing tobacco users considering or using e-cigs. What is unknown may be unique effects for e-cigs not measured herein, and clinical trials with serial bronchoscopy underway can demonstrate a direct relationship for changes in lung biomarkers.

Objectives To describe the self-reported oral health of participants in the Black Women's Health Study (BWHS), a national cohort of 59,000 Black women, and to assess factors associated with this self-report. Methods Annual follow-up of the BWHS cohort occurs via surveys. The 2011 questionnaire included oral health self-report items, on which 38,573 respondents had complete data. Sample characteristics were summarized using descriptive statistics. We assessed correlations with several covariates by estimating odds ratios using multivariable-adjusted logistic regression models. Results Those who reported fair or poor oral health were more likely to report current smoking, recent tooth loss, diabetes or hypertension diagnoses, lower education levels, obesity, and higher parity. Few factors were related to self-reported gum disease with bone loss. Conclusions The oral health of US Black women is poorly understood. Correlates of oral health in the BWHS are largely consistent with what has been observed in other populations.

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.

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 = 0.54). 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. This article is protected by copyright. All rights reserved.

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 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.

During the COVID-19 pandemic, social distancing measures often resulted in individual isolation, which can lead to adverse mental outcomes. We collected online questionnaires from 3,952 US adults to examine the impact of “shelter-in-place” guidelines on mental health, and to explore potential disparities and modifiable factors. Self-reported anxiety, depression, and PTSD symptoms were associated with more restrictive quarantine. Younger adults, women, those with lower income, more insecurity, more media exposure, reduced physical activity, or worsened family relationships were particularly affected. Targeted prevention on susceptible subpopulations, including young adults and lower SES groups, might help mitigate disparities in COVID-19-related mental health problems.

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.

Background: Somatic driver mutations in TP53 are associated with triple negative breast cancer (TNBC) and poorer outcomes. Breast cancers arising in women of African ancestry (AA) are more likely to be TNBC and have somatic TP53 mutations than non-Hispanic White (NHW) women. Missense driver mutations in TP53 are known to have different functional effects including loss-of function (LOF) or gain-of-function (GOF) activity. A subset of variants exhibit dominant negative (DNE) activity over wildtype TP53 or other TP53 family members. Methods: To determine if there were differences in TP53 mutation type by race or TNBC status we identified published and unpublished datasets with somatic mutation data, race, age, and hormone receptor status. Mutations were classified as LOF, GOF or CpG Island hotspot by published literature or type of mutation (e.g. frameshift and nonsense mutations were considered to be LOF). We used Fisher’s Exact test to assess for significant differences.Results: We identified 96 independent breast cancer studies with race and somatic TP53 mutation status available. The study comprised data from a total of 2964 women with somatic TP53 mutations: 715 (24.1%) Asian, 258 (8.7%) AA, 1931 (65.2%) NHW, and 60 (2%) Latina. Of the total TP53 mutations, 939 (31.7%) were GOF, 1739 (58.7%) were LOF, and the remaining 286 (9.6%) were not able to be classified. With respect to DNE activity, 1246 (42%) showed activity, 1190 (40.1%) showed no activity, and 528 (17.8%) were unknown status. The distribution of TP53 mutation type was similar by race and ethnicity. However, 35.8% of tumors from NHW individuals had GOF mutations compared to 29% in AA individuals (p=0.04). Mutations lacking 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: In summary, ER negative and TNBC breast tumors are less likely to have DNE+ TP53 mutations which could reflect biological processes. Larger cohorts are needed to further elucidate some of these findings.

Background An outbreak of E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) with significant morbidity and mortality was reported in 2019. While most patients with EVALI report vaping tetrahydrocannabinol (THC) oils contaminated with vitamin E acetate, a subset report only vaping with nicotine-containing electronic cigarettes (e-cigs). Whether or not e-cigs cause EVALI, the outbreak highlights the need for identifying long term health effects of e-cigs. EVALI pathology includes alveolar damage, pneumonitis and/or organizing pneumonia, often with lipid-laden macrophages (LLM). We assessed LLM in the lungs of healthy smokers, e-cig users, and never-smokers as a potential marker of e-cig toxicity and EVALI. Methods A cross-sectional study using bronchoscopy was conducted in healthy smokers, e-cig users, and never-smokers (n = 64). LLM, inflammatory cell counts, and cytokines were determined in bronchial alveolar fluids (BAL). E-cig users included both never-smokers and former light smokers. Findings High LLM was found in the lungs of almost all smokers and half of the e-cig users, but not those of never-smokers. LLM were not related to THC exposure or smoking history. LLM were significantly associated with inflammatory cytokines IL-4 and IL-10 in e-cig users, but not smoking-related cytokines. Interpretation This is the first report of lung LLM comparing apparently healthy smokers, e-cig users, and never-smokers. LLM are not a specific marker for EVALI given the frequent positivity in smokers; whether LLMs are a marker of lung inflammation in some e-cig users requires further study. 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

Globally, more than 2 million new cases of breast cancer are reported annually. The United States alone has more than 496,000 new cases every year. The worldwide prevalence is approximately 6.8 million cases. Although many risk factors for breast cancer are not modifiable, understanding the role of the factors that can be altered is critical. Alcohol consumption is a modifiable factor. Studies of alcohol in relation to breast cancer incidence have included hundreds of thousands of women. Evidence is consistent that intake, even intake of less than 10-15 grams per day, is associated with increased risk of this disease. In addition, evidence, although less extensive, shows that possible early indicators of risk, such as benign breast disease and increased breast density, are associated with alcohol consumption. Evidence is less strong for differences based on geographic region, beverage type, drinking pattern, or breast cancer subtype. Some studies have examined the association between alcohol and recurrence or survival after a breast cancer diagnosis. These findings are less consistent. Public awareness of alcohol as a risk factor for breast cancer is low, and public health measures to increase that awareness are warranted.

Breast cancer is a heterogeneous disease, characterized by molecularly and phenotypically distinct tumor subtypes, linked to disparate clinical outcomes. American women of African ancestry (AA) are more likely than those of European ancestry (EA) to be diagnosed with aggressive, estrogen receptor negative (ER−) or triple negative breast cancer, and to die of this disease. However, the underlying causes of AA predisposition to ER−/triple negative breast cancer are still largely unknown. In this study, we performed high-throughput whole-genome miRNA expression profiling in breast tissue samples from both AA and EA women. A number of differentially expressed miRNAs, i.e., DEmiRs defined as >2-fold change in expression and false discovery rate

Background We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. Methods We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. Results Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23–0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03–3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05–5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26–0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p Conclusions We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

Night shift work is associated with increased breast cancer risk, possibly from altered sleep. Epidemiologic evidence is sparse regarding sleep disturbances and breast cancer tumor markers. We examined sleep disturbance in association with breast tumor aggressiveness and mortality following diagnosis.We analyzed associations of measures of sleep disturbance in a sample of 1,122 incident breast cancer cases from the Western New York Exposures and Breast Cancer (WEB) Study. Sleep disturbance was assessed using self-administered questionnaires; responses about difficulty falling asleep, waking up frequently, having trouble staying asleep, and waking up feeling tired and worn out were used to create a summary sleep disturbance score. We used general linear models to examine associations of sleep disturbance with markers of tumor aggressiveness among cases: estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor receptor-2 (HER2) status; tumor size, stage, grade, lymph node involvement, and presence of metastasis. In addition, we examined the association between sleep disturbance and survival using Cox regression.Among breast cancer cases, sleep disturbance was higher for women with ER- / PR- tumors compared to women with ER+ / PR+ tumors, even after adjusting for potential covariates (Sleep disturbance may be associated with aggressive subtypes of breast cancer; however, further studies are needed.

Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women's Health Initiative Observational Study. Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. All analyses were conducted two-sided. Results: During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95% CI, 1.08–1.20); findings were similar in analyses limited to 34,097 never-smokers (HR, 1.12; 95% CI, 1.04–1.22). Associations were observed for breast (HR, 1.13; 95% CI, 1.03–1.23), lung (HR, 1.31; 95% CI, 1.14–1.51), esophagus (HR, 3.28; 95% CI, 1.64–6.53), gallbladder (HR, 1.73; 95% CI, 1.01–2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02–1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94–2.67). Conclusions: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255–65. ©2017 AACR.

Background Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women’s Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial. Methods The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50–79 years, recruited at 40 U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models. Results After 11 years’ cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71–1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment ( p = 0.04 for interaction). Conclusions Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers.

Objectives To identify the types of cancer patients admitted to inpatient medical rehabilitation and to describe their rehabilitation outcomes. Design Retrospective cohort study. Setting U.S. inpatient rehabilitation facilities (IRFs). Participants Adult patients (N=27,952) with a malignant cancer diagnosis admitted to an IRF with a cancer-related impairment between October 2010 and September 2012 were identified from the Uniform Data System for Medical Rehabilitation database. Interventions Not applicable. Main Outcome Measures Demographic, medical, and rehabilitation characteristics for patients with various cancer tumor types were summarized using data collected from the Inpatient Rehabilitation Facility–Patient Assessment Instrument. Rehabilitation outcomes included the percentage of patients discharged to the community and acute care settings, and functional change from admission to discharge. Functional status was measured using the FIM instrument. Results Cancer patients constituted about 2.4% of the total IRF patient population. Cancer types included brain and nervous system (52.9%), digestive (12.0%), bone and joint (8.7%), blood and lymphatic (7.6%), respiratory (7.1%), and other (11.7%). Overall, 72% were discharged to a community setting, and 16.5% were discharged back to acute care. Patients with blood and lymphatic cancers had the highest frequency of discharge back to acute care (28%). On average, all cancer patient groups made significant functional gains during their IRF stay (mean FIM total change ± SD, 23.5±16.2). Conclusions In a database representing approximately 70% of all U.S. patients in IRFs, we found that patients with a variety of cancer types are admitted to inpatient rehabilitation. Most cancer patients admitted to IRFs were discharged to a community setting and, on average, improved their function. Future research is warranted to understand the referral patterns of admission to postacute care rehabilitation and to identify factors that are associated with rehabilitation benefit in order to inform the establishment of appropriate care protocols.

Epidemiological studies suggest that short sleep duration and poor sleep quality may increase breast cancer risk. However, whether sleep is associated with breast tumor aggressiveness characteristics has largely been unexplored.The study included 4171 non-Hispanic whites (NHW) and 235 African Americans (AA) diagnosed with incident, primary, invasive breast cancer in the Women's Health Initiative (WHI) Observational Study (1994-2013). We used logistic regression to examine the association of baseline sleep (sleep duration, sleep quality, WHI Insomnia Rating Scale) with tumor grade, stage, hormone receptor status, HER2 status.In NHW, women who reported 6 h of sleep/night were more likely to have tumors classified as regional/distant stage at diagnosis compared to women who slept 7-8 h/night (adjusted odds ratio (OR): 1.25, 95% confidence interval (CI): 1.05-1.48). AA women who reported their typical night's sleep as 'average quality' or 'restless or very restless sleep' were more likely to be diagnosed with triple-negative tumors than those who reported 'sound or restful' sleep (adjusted ORs: 2.91 (1.11, 7.63) and 3.74 (1.10, 12.77), respectively).Our findings provide indications that aspects of sleep (sleep duration and quality), partially modifiable health behaviors, may be associated with development of aggressive tumor characteristics in postmenopausal women. The role of these sleep attributes may differ for NHW and AA women; however, further study in robust, racial diverse samples is needed. This study provides evidence that facets of sleep behavior are associated with the development of aggressive tumor features and these associations differ by race.

The relationship between obesity and depression is well described. However, the evidence linking depression and body mass index (BMI) across the broad range of body size is less consistent. We examined the association between depressive symptoms and BMI in a sample of adult women in the Buffalo-Niagara region between 1997 and 2001. Using logistic regression, we investigated whether increased weight status beyond normal-weight was associated with a higher prevalence of depressive symptoms, and if educational attainment modified the association between obesity and depression. There was a trend for increased weight status to be associated with higher depressive symptoms (obese II/III, OR 1.57, 95% CI 1.03–2.41), whereas higher education was associated with lower odds of depressive symptoms, in an adjusted model including BMI (more than 12 but less than 16 years, OR 0.70, 95% CI 0.49–0.98; 16 or more years of education, OR 0.61, 95% CI 0.40–0.93). The association of being obese I with depressive symptoms was different for more educated (OR 2.15, 95% CI 1.27–3.62) compared to less educated women (OR 0.90, 95% CI 0.50–1.62); the sample was larger for the more educated women and reached statistical significance. There were no differences in the association for obese II/III women in strata of education. There was evidence of risk-difference heterogeneity (0.88, 95% CI 0.84–0.93). In this population-based sample of women in western New York State, increased weight was negligibly associated with depressive symptoms. The association of being obese I with depressive symptoms was different for more compared to less educated women.

Studies show an inverse association between onion and garlic intake and risk of cancers of the lung, prostate, and stomach. There is limited evidence on the association between onion and garlic intake and breast cancer. We assessed this association in a population-based, case-control study in Puerto Rico. Incident, primary breast cancer cases (

Background A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. Methods We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. Results Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for

Background The relation of lifetime drinking trajectories to coronary heart disease is not well understood. Methods Cases hospitalized for a nonfatal acute myocardial infarction (AMI) and healthy population-based controls matched on age and sex completed a physical examination and an interview covering known AMI risk factors and a detailed lifetime drinking history. Distinct lifetime drinking trajectories based on ounces of ethanol consumed per decade between ages 10 and 59 years were derived and characterized according to lifetime drinking patterns associated with each. Sex-specific multiple logistic regression analyses were conducted to estimate AMI risk among participants who never drank regularly compared to lifetime drinking trajectories and risk associated with distinct trajectories among former and current drinkers. Results Two lifetime drinking trajectories were derived, early peak and stable. Early peak trajectories were characterized by earlier onset of regular drinking, less frequent drinking, more drinks per drinking day, fewer total drinks, more frequent drunkenness per drinking year, and reduced alcohol intake or abstention by middle age. Never drinking regularly, reported by significantly more women than men, was associated with significantly higher AMI risk than stable lifetime drinking trajectories among men and in the sex-combined analysis of former drinkers only. Compared to stable lifetime drinking trajectories, early peak trajectories were associated with significantly higher AMI risk among male former drinkers, among sex-combined former drinkers, and among female current drinkers. Conclusions Epidemiological studies of alcohol and health in populations over age 35 may have underestimated the impact of heavy episodic drinking during adolescence and emerging adulthood on the cardiovascular system.

We evaluated the association between methylation of 9 genes, SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1, and SFN in tumor samples from 720 breast cancer cases with clinicopathological features of the tumors and survival. Logistic regression was used to estimate odds ratios (OR) of methylation and Cox proportional hazards models to estimate hazard ratios (HR) between methylation and breast cancer related mortality. Estrogen receptor (ER) and progesterone receptor (PR) positivity were associated with increased SCGB3A1 methylation among pre- and post-menopausal cases. Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1-19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4-39.9; Stage III/IV OR = 5.6, 95% CI: 1.1-29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1-0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1-0.8; Stage III/IV OR = 0.6, 95% CI: 0.1-3.4). Among postmenopausal women, methylation of SYK was associated with increased tumor size (OR = 1.7, 95% CI: 1.0-2.7) and higher nuclear grade (OR = 2.0, 95% CI 1.2-3.6). Associations between methylation and breast cancer related mortality were observed among pre- but not post-menopausal women. Methylation of SCGB3A1 was associated with reduced risk of death from breast cancer (HR = 0.41, 95% CI: 0.17-0.99) as was BRCA1 (HR = 0.41, 95% CI: 0.16-0.97). CCND2 methylation was associated with increased risk of breast cancer mortality (HR = 3.4, 95% CI: 1.1-10.5). We observed differences in methylation associated with tumor characteristics; methylation of these genes was also associated with breast cancer survival among premenopausal cases. Understanding of the associations of DNA methylation with other clinicopathological features may have implications for prevention and treatment.

Extraoral translocation of oral bacteria may contribute to associations between periodontal disease and cancer. The associations among the presence of three orange-complex periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus), two red-complex periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia), and cancer risk were investigated.A total of 1,252 postmenopausal females enrolled in the Buffalo Osteoporosis and Periodontal Disease Study were followed prospectively. Baseline subgingival plaque samples were assessed for the presence of periodontal pathogens using indirect immunofluorescence. Incident cancer cases were adjudicated by staff physicians via review of medical records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of periodontal pathogens with total cancer and site-specific cancer risk in unadjusted and multivariable-adjusted models.Neither the presence of individual pathogens nor the presence of any red-complex pathogens was associated with total cancer or site-specific cancers. Borderline associations were seen among the presence of any orange-complex pathogens (F. nucleatum, P. intermedia, and C. rectus), total cancer risk (HR = 1.35, 95% CI = 1.00 to 1.84), and lung cancer risk (HR = 3.02, 95% CI = 0.98 to 9.29).No associations were found between the presence of individual subgingival pathogens and cancer risk. However, there were suggestions of borderline positive associations of the presence of any orange-complex pathogens with total cancer and lung cancer risk. The study is limited by the small number of cancer cases and the assessment of only five oral bacteria. Additional research is needed to understand the possible role of periodontal disease in carcinogenesis.

ObjectivesTo assess radiation exposure-related work history and risk of cataract and cataract surgery among radiologic technologists assisting with fluoroscopically guided interventional procedures (FGIP).MethodsThis retrospective study included 35 751 radiologic technologists who reported being cataract-free at baseline (1994–1998) and completed a follow-up questionnaire (2013–2014). Frequencies of assisting with 21 types of FGIP and use of radiation protection equipment during five time periods (before 1970, 1970–1979, 1980–1989, 1990–1999, 2000–2009) were derived from an additional self-administered questionnaire in 2013–2014. Multivariable-adjusted relative risks (RRs) for self-reported cataract diagnosis and cataract surgery were estimated according to FGIP work history.ResultsDuring follow-up, 9372 technologists reported incident physician-diagnosed cataract; 4278 of incident cases reported undergoing cataract surgery. Technologists who ever assisted with FGIP had increased risk for cataract compared with those who never assisted with FGIP (RR: 1.18, 95% CI 1.11 to 1.25). Risk increased with increasing cumulative number of FGIP; the RR for technologists who assisted with >5000 FGIP compared with those who never assisted was 1.38 (95% CI 1.24 to 1.53; p trend 3 feet (>0.9 m) (RRs for >5000 at ≤3 feet vs never FGIP were 1.48, 95% CI 1.27 to 1.74 and 1.15, 95% CI 0.98 to 1.35, respectively; pdifference=0.04). Similar risks, although not statistically significant, were observed for cataract surgery.ConclusionTechnologists who reported assisting with FGIP, particularly high-volume FGIP within 3 feet of the patient, had increased risk of incident cataract. Additional investigation should evaluate estimated dose response and medically validated cataract type.

BACKGROUND: While obesity is an established risk factor for postmenopausal breast cancer, studies of weight loss and breast cancer provide are inconsistent. Therefore, we evaluated associations between weight change and breast cancer risk in postmenopausal women in the Women’s Health Initiative (WHI) Observational Study. METHODS: Postmenopausal women (n=61,335) with no prior breast cancer and normal mammogram had body weight and height measured and body mass index (BMI) calculated at baseline and year 3. Weight change at year 3 was categorized as: stable (change < 5%), loss (change ≥ 5%), or gain (change ≥ 5%) with further assessment of weight loss intentionality by self-report. Multi-variable Cox proportional hazards regression models were used to evaluate relationships between weight change and subsequent breast cancer incidence. RESULTS: During 11.4 years (mean) follow-up with 3,061 incident breast cancers, women with weight loss (n=8,175) had a significantly lower breast cancer risk compared with stable weight women (n=41,139) (hazard ratio [HR] 0.88 95% confidence interval [CI] 0.78-0.98, P= 0.02) with no interaction by BMI. Adjustment for mammography did not alter findings (HR 0.88 95% CI 0.78-0.99) with no significant difference by weight loss intentionality. Weight gain (≥ 5%) (n=12,021) was not associated with breast cancer risk (HR 1.02 95% CI 0.93-1.11) but was associated with higher triple negative breast cancer incidence (HR 1.54 95% CI 1.16-2.05). CONCLUSIONS: Postmenopausal women who lost weight have lower breast cancer risk than those with stable weight. These findings suggest that postmenopausal women who lose weight may reduce their breast cancer risk.

Background Bisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women’s Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI. Patients and methods The association between oral bisphosphonate use and lung cancer risk was examined in 151 432 postmenopausal women enrolled into the WHI in 1993–1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates. Results After a mean follow-up of 13.3 years, 2511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio = 0.91; 95% confidence intervals, 0.80–1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (hazard ratio = 0.57, 95% confidence interval, 0.39–0.84; P Conclusion In this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings.

Mutations in the p53 gene are among the most frequent genetic events in human cancer and may be triggered by environmental and occupational exposures. We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations. Using tumor blocks from incident cases from a case-control study in western New York, we screened for p53 mutations in exons 2-11 using the Affymetrix p53 Gene Chip array and analyzed case-case comparisons using logistic regression. The p53 mutation frequency among cases was 28.1 %; 95 % were point mutations (13 % of which were silent) and the remainder were single base pair deletions. Sixty seven percent of all point mutations were transitions; 24 % of them are G:C>A:T at CpG sites. Positive p53 mutation status was associated with poorer differentiation (OR, 95 % CI 2.29, 1.21-4.32), higher nuclear grade (OR, 95 % CI 1.99, 1.22-3.25), and increased Ki-67 status (OR, 95 % CI 1.81, 1.10-2.98). Cases with P53 mutations were more likely to have a combined ER-positive and PR-negative status (OR, 95 % CI 1.65, 1.01-2.71), and a combined ER-negative and PR-negative status (OR, 95 % CI 2.18, 1.47-3.23). Body mass index >30 kg/m(2), waist circumference >79 cm, and waist-to-hip ratio >0.86 were also associated with p53 status; obese breast cancer cases are more likely to have p53 mutations (OR, 95 % CI 1.78, 1.19-2.68). We confirmed that p53 mutations are associated with less favorable tumor characteristics and identified an association of p53 mutation status and adiposity.

Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility.

Documentation of a new or worsened pressure ulcer is a new, required quality indicator for all inpatient rehabilitation facilities (IRFs) in the United States; however, there is little research regarding risk factors for pressure ulcers among patients seen in IRFs.To examine the risk factors for development of a new or worsened pressure ulcer among patients seen in IRFs.A retrospective cohort study.IRFs in the United States.IRF patients more than 18 years of age, with documented new or worsened pressure ulcer during their rehabilitation stay (n = 2766) and IRF patients with no new or worsened pressure ulcer documented from admission to discharge (n = 190,996) discharged October 2008 to September 2011, included in the Uniform Data System for Medical Rehabilitation database.Multiple logistic regression analysis was used to estimate risk factors for the development of a new or worsened pressure ulcer utilizing data captured in the Centers for Medicare and Medicaid Services (CMS) payment document. Examined were demographic variables, including age and gender, medical variables, including impairment type and presence of comorbidities, and functional status, as measured through the Functional Independence Measure (FIM) instrument.Development of a new or worsened pressure ulcer in patients during the rehabilitation stay compared to patients with no documented pressure ulcer or no worsened ulcer.Admission FIM total was strongly associated with development of a new or worsened pressure ulcer, P.001 in analyses of all patients and for each of the 3 impairment-specific groups with the highest rate of ulcer development among spinal cord injury, orthopedic, and amputation cases. CMS comorbidity tier was also significantly associated with ulcers in all models. Other variables that entered one or more models included increased age, male gender, and use of a wheelchair.Admission FIM total and CMS comorbidity tier may be useful in the identification of patients at risk for development of new or worsened pressure ulcers in IRFs. Identification of pressure ulcer risk factors has important implications for individual plan-of-care decisions as well as for resource provisions during the rehabilitation stay.

Background: Use of calcium channel blockers (CCBs) has been associated with increased risk of breast cancer in some, but not all, studies. Differences in reported associations from prior studies may be due, in part, to inadequate control of confounding factors. Methods: Participants were 28,561 postmenopausal women from the Women's Health Initiative who reported use of either CCBs or other antihypertensive medications (AHMs) at baseline; 1,402 incident breast cancer cases were diagnosed during 12 years of follow-up. Adjusted Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the associations between CCB use relative to other AHM use and breast cancer risk. Results: Use of CCBs was not associated with breast cancer risk (HR, 1.06; 95% CI, 0.94–1.20) relative to use of other AHMs. Associations approximated the null value when CCBs were considered by duration of use, length of action, or drug class. Conclusions: We provide additional evidence that CCBs do not influence breast cancer risk in postmenopausal women. Impact: The results from this study, which includes strong control for potential confounding factors, cast doubt on increases in risk with CCBs. Cancer Epidemiol Biomarkers Prev; 26(8); 1345–8. ©2017 AACR.

Objective To examine the association between the Medicare pressure ulcer quality indicator (the development of new or worsened pressure ulcers) and rehabilitation outcomes among Medicare patients seen in an inpatient rehabilitation facility (IRF). Design Retrospective descriptive study. Setting IRFs subscribed to the Uniform Data System for Medical Rehabilitation. Participants Nearly 500,000 IRF Medicare patients who were discharged between January 2013 and September 2014 were examined. Interventions Not applicable. Main Outcome Measures Functional independence, functional change (gain), and discharge destination. Results The pressure ulcer quality indicator was associated with poorer rehabilitation outcomes; patients were less likely to achieve functional independence (odds ratio [OR], .47; 95% confidence interval [CI], .44–.51), were less likely to be discharged to a community setting (OR, .88; 95% CI, .82–.95), and made less functional gain during their IRF stay (a difference of 6 FIM points). Conclusions These results support that the pressure ulcer quality indicator is associated with lower quality of rehabilitation outcomes; however, given that those patients with a new or worsened pressure injury still made functional gains and most were discharged to the community, the risk of pressure injury development should not preclude the admission of these cases to an IRF.

The use of electronic cigarettes (e-cigs) is increasing rapidly, but their effects on lung toxicity are largely unknown. Smoking is a well-established cause of lung cancer and respiratory disease, in part through inflammation. It is plausible that e-cig use might affect similar inflammatory pathways. E-cigs are used by some smokers as an aid for quitting or smoking reduction, and by never smokers (e.g., adolescents and young adults). The relative effects for impacting disease risk may differ for these groups. Cell culture and experimental animal data indicate that e-cigs have the potential for inducing inflammation, albeit much less than smoking. Human studies show that e-cig use in smokers is associated with substantial reductions in blood or urinary biomarkers of tobacco toxicants when completely switching and somewhat for dual use. However, the extent to which these biomarkers are surrogates for potential lung toxicity remains unclear. The FDA now has regulatory authority over e-cigs and can regulate product and e-liquid design features, such as nicotine content and delivery, voltage, e-liquid formulations, and flavors. All of these factors may impact pulmonary toxicity. This review summarizes current data on pulmonary inflammation related to both smoking and e-cig use, with a focus on human lung biomarkers. Cancer Epidemiol Biomarkers Prev; 26(8); 1175–91. ©2017 AACR.

Background Few studies have reported associations between periodontitis and cardiovascular disease ( CVD ) risk in older women, which is the objective of the present investigation. Methods and Results Participants were 57 001 postmenopausal women ages 55 to 89 years (mean 68 years; >85% 60 and older) who were enrolled (1993–1998) in the Women's Health Initiative Observational Study, and were without known CVD when history of periodontitis and edentulism was assessed by questionnaire at study Year‐5 (1998–2003). There were 3589 incident CVD events and 3816 total deaths during a mean follow‐up of 6.7 years. In multivariable analysis, periodontitis was not associated with CVD events, but was associated with higher total mortality (hazard ratio ( HR )=1.12, 95% CI : 1.05–1.21). Edentulism was associated with higher age‐ and smoking‐adjusted risks of CVD ( HR =1.42, 95% CI : 1.27–1.59) and mortality ( HR =1.47, 95% CI : 1.32–1.63). Further adjustment eliminated the association with CVD , but mortality remained significantly increased ( HR =1.17, 95% CI : 1.02–1.33). Stratification on age, race‐ethnicity, smoking, and diabetes mellitus yielded comparable results; however, edentulism was more strongly associated with CVD in women reporting ≥1 dental visit ( HR =1.57) compared with HR 1.03, interaction P =0.004) annually. Conclusions In community‐dwelling older women, edentulism was associated with increased risks of CVD and total mortality, and presence of periodontitis, which is more prevalent than edentulism, was associated with 17% higher mortality rate. These findings suggest that improving periodontal condition of the general population could reduce overall mortality.

Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97–1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19–3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03–1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

To investigate the association between breastfeeding and endometrial cancer risk using pooled data from 17 studies participating in the Epidemiology of Endometrial Cancer Consortium.We conducted a meta-analysis with individual-level data from three cohort and 14 case-control studies. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between breastfeeding and risk of endometrial cancer using multivariable logistic regression and pooled using random-effects meta-analysis. We investigated between-study heterogeneity with I and Q statistics and metaregression.After excluding nulliparous women, the analyses included 8,981 women with endometrial cancer and 17,241 women in a control group. Ever breastfeeding was associated with an 11% reduction in risk of endometrial cancer (pooled OR 0.89, 95% CI 0.81-0.98). Longer average duration of breastfeeding per child was associated with lower risk of endometrial cancer, although there appeared to be some leveling of this effect beyond 6-9 months. The association with ever breastfeeding was not explained by greater parity and did not vary notably by body mass index or histologic subtype (grouped as endometrioid and mucinous compared with serous and clear cell).Our findings suggest that reducing endometrial cancer risk can be added to the list of maternal benefits associated with breastfeeding. Ongoing promotion, support, and facilitation of this safe and beneficial behavior might therefore contribute to the prevention of this increasingly common cancer.

Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients. Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes. Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced). Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival. Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470–3. ©2017 AACR.

p16(INK4a) is a tumor suppressor gene, frequently hypermethylated in breast cancer; this epigenetic silencing of p16(INK4a) occurs early in carcinogenesis. The risk factors and functional consequences of p16(INK4a) methylation are unknown. Alcohol consumption, a breast cancer risk factor, impedes folate metabolism and may thereby alter gene methylation since folate plays a pivotal role in DNA methylation. In a cross-sectional study of 138 women with no history of breast cancer who underwent reduction mammoplasty, we studied breast cancer risk factors, plasma and breast folate concentrations, variation in one-carbon metabolism genes, p16(INK4a) promoter methylation and P16 protein expression. Logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). p16(INK4a) methylation was negatively correlated with P16 expression (r = -0.28; P = 0.002). Alcohol consumption was associated with lower breast folate (P = 0.03), higher p16(INK4a) promoter methylation (P = 0.007) and less P16 expression (P = 0.002). Higher breast folate concentrations were associated with lower p16(INK4a) promoter methylation (P = 0.06). Genetic variation in MTRR (rs1801394) and MTHFD1 (rs1950902) was associated with higher p16 (INK4a) promoter methylation (OR = 2.66, 95% CI: 1.11-6.42 and OR = 2.72, 95% CI: 1.12-6.66, respectively), whereas variation in TYMS (rs502396) was associated with less P16 protein expression (OR = 0.22, 95% CI: 0.05-0.99). Given that this is the first study to indicate that alcohol consumption, breast folate and variation in one-carbon metabolism genes are associated with p16(INK4a) promoter methylation and P16 protein expression in healthy tissues; these findings require replication.

Background: Circulating adipokines may be associated with breast cancer risk. Genetic variants governing adipokines and adipokine receptors may also predict risk, but their effect on breast adipokine concentrations is unknown. Methods: We conducted a cross-sectional analysis of functional SNPs in 5 adipokine genes [adiponectin, leptin (LEP), and their receptors] among 85 cancer-free women who were undergoing reduction mammoplasty. Results: In multivariable-adjusted regression models, compared with the common GG genotype, the AA genotype of the LEP A19G SNP was associated with 27% lower plasma adiponectin [ratio, 0.73; 95% confidence interval (CI), 0.54–0.98] and leptin (ratio, 0.73; 95% CI, 0.55–0.96). Women with the AG genotype of LEP A19G had 39% lower breast leptin (ratio, 0.61; 95% CI, 0.39–0.97) compared with those with the GG genotype. No associations were observed for SNPs in the remaining genes. Conclusions: Genetic variation in LEP may alter endogenous adipokine concentrations in circulation and in breast tissues. Impact: These preliminary findings may support the hypothesis that genetic variation in adipokine genes modifies circulating adipokine concentrations and possibly leptin concentrations in local breast tissues, which may be associated with breast cancer risk. Cancer Epidemiol Biomarkers Prev; 23(8); 1559–68. ©2014 AACR.

While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women.Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women's Health Initiative Observational Study. History of PD (prevalence of 26.1 %) was self-reported, and 754 incident lung cancer cases occurred during an average 6.8 (SD ± 2.6) years of follow-up. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR 1.24, 95 % CI 1.07-1.45). There was a positive additive interaction between PD with pack-years of smoking (p = 0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR 1.02, 95 % CI 0.68-1.53).Periodontal disease was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination.

Background: Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality. Methods: Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women's Health Initiative's Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles. Results: Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55–0.99; Ptrend = 0.043) and a 42% lower risk of death from non–breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38–0.87; Ptrend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60–1.40; Ptrend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER+ tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38–0.79; Ptrend = 0.0009). Conclusion: Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non–breast cancer causes. Impact: Breast cancer survivors may experience improved survival by adhering to U.S. dietary guidelines. Cancer Epidemiol Biomarkers Prev; 23(4); 575–83. ©2014 AACR.

American women of African ancestry (AA) are more likely than European-Americans (EA) to be diagnosed with aggressive, estrogen receptor (ER) negative breast tumors; mechanisms underlying these disparities are poorly understood. We conducted a genome wide (450K loci) methylation analysis to determine if there were differences in DNA methylation patterns between tumors from AA and EA women and if these differences were similar for both ER positive and ER negative breast cancer. Methylation levels at CpG loci within CpG islands (CGI)s and CGI-shores were significantly higher in tumors (n=138) than in reduction mammoplasty samples (n=124). In hierarchical cluster analysis, there was separation between tumor and normal samples, and in tumors, there was delineation by ER status, but not by ancestry. However, differential methylation analysis identified 157 CpG loci with a mean β value difference of at least 0.17 between races, with almost twice as many differences in ER-negative tumors compared to ER-positive cancers. This first genome-wide methylation study to address disparities indicates that there are likely differing etiologic pathways for the development of ER negative breast cancer between AA and EA women. Further investigation of the genes most differentially methylated by race in ER negative tumors can guide new approaches for cancer prevention and targeted therapies, and elucidate the biologic basis of breast cancer disparities.

There is growing evidence that body size in early life influences lifetime breast cancer risk, but little is known for African American (AA) women.We evaluated body size during childhood and young adulthood and breast cancer risk among 1,751 cases [979 AA and 772 European American (EA)] and 1,673 controls (958 AA and 715 EA) in the Women's Circle of Health Study. Odds ratio (OR) and 95 % confidence intervals (CI) were computed using logistic regression models while adjusting for potential covariates.Among AA women, being shorter at 7-8 years compared to peers was associated with increased postmenopausal breast cancer risk (OR 1.68, 95 % CI 1.02-2.74), and being heavier at menarche with decreased postmenopausal breast cancer risk, although of borderline significance (OR 0.45, 95 % CI 0.20-1.02). For EA women, being shorter from childhood through adolescence, particularly at menarche, was associated with reduced premenopausal breast cancer risk (OR 0.55, 95 % CI 0.31-0.98). After excluding hormone replacement therapy users, an inverse association with postmenopausal breast cancer was found among EA women reporting to be heavier than their peers at menarche (OR 0.18, 95 % CI 0.04-0.79). The inverse relationship between BMI at age 20 and breast cancer risk was stronger and only statistically significant in EA women. No clear association with weight gain since age 20 was found.Findings suggest that the impact of childhood height on breast cancer risk may differ for EA and AA women and confirm the inverse association previously reported in EA populations with adolescent body fatness, in AA women.

Chronic lung disease is exacerbated by comorbid psychiatric issues and treatment of depression may improve disease symptoms. We sought to add to the literature as to whether depression is associated with pulmonary function in healthy adults.In 2551 healthy adults from New York State, we studied the association of depression via the Center for Epidemiologic Studies Depression scale (CES-D) scale score and forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) using general linear models and a cross-sectional design.We identified statistically significant inverse trends in FEV1, FVC, FEV1%, and FVC% by CES-D category, especially in ever-smokers and men. When adjusted for covariates, the difference in FEV1 and FEV1% for smokers with more than 18.5 lifetime pack-years from CES-D scores 0 to 3 to 16 or more (depressed) is approximately 0.25 l and 5.0% (adjusted p values for trend are.001 and .019, respectively). In men, we also observed statistically significant inverse trends in pulmonary function with increasing CES-D.We identified an inverse association of depressive symptoms and pulmonary function in healthy adults, especially in men and individuals with a heavy smoking history. Further studies of these associations are essential for the development and tailoring of interventions for the prevention and treatment of chronic lung disease.

Lymph node metastases and tumor characteristics predict breast cancer prognosis but correlate imperfectly with likelihood of metastatic relapse. Discovery of genetic polymorphisms affecting metastasis may improve identification of patients requiring aggressive adjuvant therapy to prevent recurrence. We investigated associations between several variants in the BRMS1 and SIPA1 metastasis-modifying genes and lymph node metastases, tumor subtype and grade, recurrence, disease-free survival, and overall survival. This cross-sectional and prospective prognostic analysis included 859 patients who received surgery for incident breast cancer at Roswell Park Cancer Institute, participated in the DataBank and BioRepository shared resource, and had DNA, clinical, and pathology data available for analysis. Genotyping for BRMS1 (rs11537993, rs3116068, and rs1052566) and SIPA1 (rs75894763, rs746429, rs3741378, and rs2306364) polymorphisms was performed using Sequenom® iPLEX Gold and Taqman® real-time PCR assays. Logistic and Cox proportional hazards regressions were used to estimate odds ratios (OR) and hazard ratios (HR), respectively. BRMS1 rs1052566 heterozygous individuals were more likely to have node-positive tumors (OR = 1.58, 95 % CI 1.13–2.23), although there was no dose–response relationship, and those with at least one variant allele were less likely to have the luminal B subtype (AG + AA: OR = 0.59, 95 % CI 0.36–0.98). BRMS1 rs3116068 was associated with increased likelihood of having the luminal B and the HER2-enriched tumor subtype (P trend = 0.03). Two SIPA1 SNPs, rs746429 and rs2306364, were associated with decreased risk of triple-negative tumors (P trend = 0.04 and 0.07, respectively). Presence of 8 or more risk alleles was associated with an increased likelihood of having a node-positive tumor (OR = 2.14, 95 % CI 1.18–3.36, P trend = 0.002). There were no significant associations with survival. Polymorphisms in metastasis-associated genes may be related to tumor characteristics and lymph node metastasis, but not survival. Future evaluation of metastasis-modifying gene variants is necessary to better understand the biology of metastasis.

The use of geocoded historical residence as proxy for retrospective assessment of exposure in early life is increasing in epidemiological studies of chronic health outcomes. Dealing with historical residence poses challenges, primarily due to higher uncertainties associated with data collection and processing. A possible source of bias is connected with the exclusion of subjects, who cannot, for various reasons, be geocoded. We evaluated the potential bias that may arise due to incomplete geocoding, using birth residence data collected as part of a population-based case-control study of breast cancer in western New York state. We found that geocoded and non-geocoded populations did not differ in the distribution of most risk factors compared, and that the geocoding status did not modify the spatial patterns of the study populations. However, the results emphasize the need for epidemiological studies to consider the potential biases that may be introduced by geocoding of historical residence when investigating retrospectively chronic disease and early-life exposure.