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.

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.

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.

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.

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.

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.

Glycemic Index, Glycemic Load, and Risk of Ovarian Cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cohort.

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.

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

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

Lung cancer mortality associated with protracted low-dose occupational radiation exposures and smoking behaviors in U.S. radiologic technologists, 1983-2012.

In the Japanese atomic bomb survivors, risk of lung cancer has been shown to increase with greater acute exposure to ionizing radiation. Although similar findings have been observed in populations exposed to low-dose, protracted radiation, such studies lack information on cigarette smoking history, a potential confounder. In a cohort of 106 068 U.S. radiologic technologists, we examined the association between estimated cumulative lung absorbed dose from occupational radiation exposure and lung cancer mortality. Poisson regression models, adjusted for attained age, sex, birth cohort, pack-years smoked and years since quitting smoking, were used to calculate linear excess relative risks (ERR) per 100 mGy, using time-dependent cumulative lung absorbed dose, lagged 10 years. Mean cumulative absorbed dose to the lung was 25 mGy (range: 0-810 mGy). During the 1983 to 2012 follow-up, 1090 participants died from lung cancer. Greater occupational radiation lung dose was not associated with lung cancer mortality overall (ERR per 100 mGy: -0.02, 95% CI: <0-0.13). However, significant dose-response relationships were observed for some subgroups, which might be false-positive results given the number of statistical tests performed. As observed in other studies of radiation and smoking, the interaction between radiation and smoking appeared to be sub-multiplicative with an ERR per 100 mGy of 0.41 (95% CI: 0.01-1.15) for those who smoked <20 pack-years and -0.03 (95% CI: <0-0.15) for those who smoked ≥20 pack-years. Our study provides some evidence that greater protracted radiation exposure in the low-dose range is positively associated with lung cancer mortality.

Onion and Garlic Intake and Breast Cancer, a Case-Control Study in Puerto Rico.

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 (n = 314) were identified among women aged 30-79 from hospital and clinic records. Controls (n = 346) were women with no history of cancer other than nonmelanoma skin cancer, residents of the same area. Dietary intake was estimated using a food frequency questionnaire. Total onion and garlic intake included sofrito (a popular garlic- and onion-based condiment) intake frequency. Unconditional logistic regression assessed the association between onion and garlic consumption and breast cancer adjusting for age, education, parity, family history, body mass index, age at menarche, total energy, and smoking. Inverse associations with breast cancer were observed for moderate (OR (odds ratio) = 0.59, 95% CI (confidence interval): 0.35, 1.01) and high consumption (OR = 0.51, 95% CI: 0.30, 0.87) compared to low consumption of onion and garlic (Ptrend = 0.02). Results were similar when stratified by menopausal status. Study results suggest that high onion and garlic consumption is protective against breast cancer in this population.

Differences in microRNA expression in breast cancer between women of African and European ancestry.

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 <0.05, were identified as up- or downregulated by tumor ER status or by ancestry. We found that among 102 ER-subtype-related DEmiRs identified in breast tumors, the majority of these DEmiRs were race specific, with only 23 DEmiRs shared in tumors from both AAs and EAs; this finding indicates that there are unique subsets of miRNAs differentially expressed between ER- and ER positive tumors within AAs versus EAs. Our overall results support the notion that miRNA expression patterns may differ not only by tumor subtype but by ancestry, indicating differences in tumor biology and heterogeneity of breast cancer between AAs and EAs. These results will provide the basis for further functional analysis to elucidate biological differences between AAs and EAs and to help develop targeted treatment strategies to reduce disparities in breast cancer.

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

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 < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors. CONCLUSIONS: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer.

Weight loss and breast cancer incidence in postmenopausal women.

BACKGROUND: Although obesity is an established risk factor for postmenopausal breast cancer, the results of weight loss and breast cancer studies are inconsistent. Therefore, we evaluated associations between weight change and breast cancer risk in postmenopausal women in the Women's Health Initiative Observational Study. METHODS: Postmenopausal women (n = 61,335) who had no prior breast cancer and a 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 (<5%), loss (≥5%), or gain (≥5%) with further assessment of weight loss intentionality by self-report. Multivariable Cox proportional hazard regression models were used to evaluate relationships between weight change and subsequent breast cancer incidence. RESULTS: During a mean follow-up of 11.4 years with 3061 incident breast cancers, women with weight loss (n = 8175) had a significantly lower risk of breast cancer compared with women whose weight remained stable (n = 41,139) (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78-0.98; P = .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 lose 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.

Active and secondhand smoke exposure throughout life and DNA methylation in breast tumors.

PURPOSE: Tobacco smoke exposure has been associated with altered DNA methylation. However, there is a paucity of information regarding tobacco smoke exposure and DNA methylation of breast tumors. METHODS: We conducted a case-only analysis using breast tumor tissue from 493 postmenopausal and 225 premenopausal cases 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 measured with pyrosequencing. Participants reported their secondhand smoke (SHS) and active smoking exposure for seven time periods. Unconditional logistic regression was used to estimate odds ratios (OR) of having methylation higher than the median. RESULTS: SHS exposure was associated with tumor DNA methylation among postmenopausal but not premenopausal women. Active smoking at certain ages was associated with increased methylation of GSTP1, FHIT, and CDKN2A and decreased methylation of SCGB3A1 and BRCA1 among both pre- and postmenopausal women. CONCLUSION: Exposure to tobacco smoke may contribute to breast carcinogenesis via alterations in DNA methylation. Further studies in a larger panel of genes are warranted.

Lifetime Drinking Trajectories and Nonfatal Acute Myocardial Infarction.

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.

Cataract risk in US radiologic technologists assisting with fluoroscopically guided interventional procedures: a retrospective cohort study.

OBJECTIVES: To assess radiation exposure-related work history and risk of cataract and cataract surgery among radiologic technologists assisting with fluoroscopically guided interventional procedures (FGIP). METHODS: This 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. RESULTS: During 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 <0.001). These associations were more pronounced for FGIP when technologists were located ≤3 feet (≤0.9 m) from the patient compared with >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. CONCLUSION: Technologists 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.

Cardiometabolic risk factors and survival after breast cancer in the Women's Health Initiative.

BACKGROUND: Few studies have examined the relationship between cardiometabolic risk factors linked to metabolic syndrome and mortality among women with breast cancer. METHODS: We used the Women's Health Initiative to evaluate the relationship between cardiometabolic risk factors, including waist circumference (WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and their relation with death from breast cancer, cardiovascular disease (CVD), and other causes among 8641 women with local or regional stage invasive breast cancer. Cox proportional hazards models were used to estimate hazard ratios, and 95% confidence intervals, adjusted for important predictors of survival. RESULTS: After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which were due to breast cancer. Most participants (55.7%) had at least 2 cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk factors was associated with higher risk of CVD and other-cause mortality (P trend < .001 for both), but not with breast cancer mortality (P trend = .86). Increased WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI, 1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses stratified by race, hormone receptor status, or after an analysis of cases diagnosed within 5 years after baseline. CONCLUSIONS: Among women with early stage breast cancer, cardiometabolic risk factors are significantly associated with cardiovascular and other-cause mortality, but not breast cancer mortality. Cancer 2018;124:1798-807. © 2018 American Cancer Society.

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors.

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 < 0.01). 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.