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.

Prevalence of metabolic syndrome among Vietnamese adult employees.

BACKGROUND AND AIMS: Metabolic syndrome (MtS) is associated with increased risk of many health disorders, especially cardiovascular diseases. In Vietnam, study examining MtS is meager and especially lacking for the workforce. We estimated the prevalence of MtS and its associated factors among Vietnamese employees. METHODS AND RESULTS: We analyzed secondary data of annual health check of employees of 300 Vietnamese companies from the Vinmec Healthcare System. We used three definitions for MtS: International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and NCEP ATP III-Asia. Of 57,997 participants evaluated, 48.5 % were males and 66.2 % were younger than 40 years old. The unadjusted MtS prevalence was 8.4 % (IDF), 10.2 % (NCEP ATP III), and 16.0 % (NCEP ATP III-Asia). The age-sex adjusted prevalence of MtS (NCEP ATP III-Asia) was 21.8 % (95 % confidence interval (CI): 21.4 %, 22.2 %). MtS prevalence increased with age, reached 49.6 % for age ≥60. The aging related increase was more remarkable in females than males (prevalence ratio (PR) (95 % CI) for age ≥60 comparing to age <30 years old in males vs. females was 4.0 (3.6, 4.3) vs. 20.1 (17.7, 22.9)). High blood triglyceride (83.4 %) and abdominal obesity (74.5 %) were the predominant contributors to MtS. CONCLUSION: In this relatively young Vietnamese working population, 16 % had MtS with high triglyceride and abdominal obesity being the predominant contributors. These findings emphasize the need for developing effective high triglyceride and abdominal obesity prevention and control programs to curb the emerging epidemic of metabolic disorders in the workforce.

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

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

Sugar-Sweetened Soda Consumption and Total and Breast Cancer Mortality: The Western New York Exposures and Breast Cancer (WEB) Study.

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; P trend < 0.01) and breast cancer mortality (HR = 1.85; 95% CI, 1.16-2.94; P trend < 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.

Mediterranean diet and all-cause mortality: A cohort of Italian men.

BACKGROUND AND AIMS: The present study analyzes the relation between diet and all-cause mortality in a cohort of Italian men residing in different regions of Italy. METHODS AND RESULTS: The cohort was established using the members of the Associazione Nazionale Alpini, a voluntary organization that enlists individuals who have served in the Alpine troup; a mountain warfare infantry corps of the Italian Army. For the purpose of these analyses a total of 5049 participants were followed for an average of seven years. At baseline information was collected regarding age, education, life style habits, with special emphasis on diet (with the use of a validated dietary questionnaire), smoking and alcohol use. A total of 190 deaths were ascertained. In multivariate analyses the consumption of a Mediterranean type diet was inversely associated with mortality. Additional findings of relevance include: an inverse association between mortality and intake of vegetable fats and proteins, monounsaturated (MUFA) fats of vegetable origins, starch and folic acid. Positive association were evident between mortality and intake of animal fats, MUFA of animal origins and sugar. CONCLUSIONS: This study, focusing on a homogenous cohort characterized by a varied intake and high intake of monounsaturated fats, confirms the inverse association between a Mediterranean type diet and mortality and points out that the nature of the MUFA may be relevant for their effects on health. In addition, the study confirms that fats of animal origins and dietary sugar are associated with an overall deleterious effect on mortality.

The Association Between Low Serum Cholesterol and Non-Cardiovascular Mortality among Italian Males and Females: A Nine- Year Prospective Cohort Ctudy

Background: No study to date provides evidence suggesting that lower cholesterol is associated with excess death in non-cardiovascular disease (NCVD). This study aimed to determine the association between low cholesterol level and NCVD mortality. Methods: A nine-year cohort study was conducted on 3,079 male and 26,005 female Italians aged 20-69 years old. The Cox proportional hazard models implied a hazard ratio with 95% confidence interval for association. Results: Among males, there were significant inverse associations between the lowest cholesterol decile (< 160mg/dl) hazard ratio and all-cause deaths and non-cardiovascular deaths, 1.50 (1.19-1.89) and 2.06 (1.54-2.74), respectively. Among females, there was a significant inverse association of lowest and fourth cholesterol deciles, 1.53 (1.01-2.34); 1.52 (1.06-2.18) hazard ratio for all-cause deaths and risk for non-cardiovascular deaths in the same deciles 1.52 (0.91-2.50); 1.78 (1.16-2.71), respectively. Remarkably, in depth analysis for NCVD, found significant inverse associations hazard of cholesterol <160 mg/dl for cancer, non-cancer liver dysfunction (NCLD), other non-cancer-non- CVD in males and only NCLD death was significant in females. Conclusion: Among males, there were significant inverse hazard associations between the lowest cholesterol decile and all-cause and non-CVD deaths . Among females, there were significant inverse hazard associations of lowest and fourth cholesterol decile for all-cause and also risk first and fourth deciles for non-CVD mortality.

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.

The Mutual Impact of Smoking and Low Cholesterol on All-Cause, Non-Cardiovascular, and Cardiovascular Mortalities in Males.

The aim of the current study was to examine the possible relationship between the mutual effects of smoking and low cholesterol on all-cause, non-cardiovascular, and cardiovascular mortalities in males. This is a prospective cohort study of 30,179 males sampled from the Risk Factors and Life Expectancy (RIFLE) studies in the Italian population. The RIFLE data are from 19 different large-scale studies over a 9.5-year follow-up period. The Cox Proportional Hazard model was applied to analyze the data. The associations are presented as hazard ratios (HRs) with 95% confidence interval (CI). Cholesterol data were reported in categories. There were significant mortality risk mutual associations for never-smokers and those in the low cholesterol category (<160 mg/dl) for all-cause (HR = 3.13, 95% CI [1.69, 5.80]), and non-cardiovascular disease (CVD) (HR = 6.51, 95% CI [2.19, 19.33]) mortality in men with an insignificant risk for CVD mortality (HR = 1.90, 95% CI [0.85, 4.22]). There were significant mortality risk associations of the mutual effects of ex-smokers and low cholesterol for non-CVD in the first to third cholesterol categories (HR = 2.50, 95% CI [1.40, 4.46]; HR = 2.65, 95% CI [1.50, 4.71]; HR = 2.12, 95% CI [1.17, 3.82], respectively), but no significant findings for all-cause and CVD deaths. Furthermore, there were significant mortality risk association of mutual effects of current-smokers and low cholesterol for non-CVD (HR = 1.56, 95% CI [1.11, 2.28]) in the first category of cholesterol level, but insignificant risk associations for all-cause deaths (HR = 1.21, 95% CI [0.89, 1.66]). Interestingly, findings indicate a mutual protective association for current-smokers and low cholesterol (<160 mg/dl) for CVD risk in males (HR = 0.42, 95% CI [0.19, 0.91]). Findings of this study identified significant mortality risk association for mutual effects of never-smokers, ex-smokers, and low cholesterol for non-CVD. However, there is significant protective association for current-smokers and low cholesterol for CVD.

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.

Sleep and Breast Cancer in the Western New York Exposures and Breast Cancer (WEB) Study.

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (P for trend = .02). Results suggest that the association of sleep quality differs by menopausal status, where mild sleep disturbance is associated with higher breast cancer mortality in premenopausal women; however, we had a relatively small sample size. CONCLUSIONS: Sleep disturbance may be associated with aggressive subtypes of breast cancer; however, further studies are needed.

Is low cholesterol a risk factor for cancer mortality?

Although a large number of studies have shown the associations of high plasma lipid profile levels with cancer, few studies demonstrate the association between low serum cholesterol (<160 mg/dl) and risk for cancer mortality. The aim of this study was to determine the association of low serum cholesterol level as a risk factor for mortality in cancer. The prospective cohort studies were conducted on 19 of 52 cohort studies including 30 179 male and 26 005 female participants who were followed up for 9 years. Cox proportion hazard model was applied to analyze these data. The associations are presented as hazard ratios (HRs) with 95% confidence intervals (CI). The statistical package for the social sciences software was used for analysis. The multivariate analysis results showed risk associations with low serum cholesterol for the first decile among male participants (cancer: HR=1.52, 95% CI: 1.06-2.18; noncancer liver dysfunction: HR=10.73, 95% CI: 3.74-30.18) and female participants (cancer: HR=1.03, 95% CI: 0.52-2.05; noncancer liver dysfunction: HR=25.8, 95% CI: 3.09-217.70). Furthermore, in the second decile, this association among male patients (noncancer liver dysfunction: HR=3.73, 95% CI: 1.16-11.95) had a statistically significant result. For the remaining deciles in both sexes, cancer and noncancer liver dysfunction has some risk or protective association, although not significant. Findings of this study indicated an inverse association between low serum cholesterol and cancer and noncancer liver dysfunction mortality.

DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study.

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.

Single-Nucleotide Polymorphisms and Markers of Oxidative Stress in Healthy Women.

PURPOSE: There is accumulating evidence that oxidative stress is an important contributor to carcinogenesis. We hypothesized that genetic variation in genes involved in maintaining antioxidant/oxidant balance would be associated with overall oxidative stress. METHODS: We examined associations between single nucleotide polymorphisms (SNPs) in MnSOD, GSTP1, GSTM1, GPX1, GPX3, and CAT genes and thiobarbituric acid-reactive substances (TBARS), a blood biomarker of oxidative damage, in healthy white women randomly selected from Western New York (n = 1402). We used general linear models to calculate age-adjusted geometric means of TBARS across the variants. We also examined the associations within strata of menopausal status. RESULTS: For MnSOD, being heterozygous was associated with lower geometric means of TBARS (less oxidative stress), 1.28 mg/dL, compared to homozygous T-allele or homozygous C-allele,1.35 mg/dL, and 1.31 mg/dL correspondingly (p for trend = 0.01). This difference remained among postmenopausal women, 1.40 mg/dL for TT, 1.32 mg/dL for TC, and 1.34mg/dL for CC (p for trend 0.015); it was attenuated among premenopausal women. SNPs in the other genes examined (GSTP1, GSTM1, GPX1, GPX3, and CAT) were not associated with TBARS. CONCLUSIONS: Our findings suggest that genetic variation in MnSOD gene may be associated with oxidative status, particularly among postmenopausal women.

Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio.

Adiposity is associated with p53 gene mutations in breast cancer.

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.

Alcohol intake, reproductive hormones, and menstrual cycle function: a prospective cohort study.

BACKGROUND: Although habitual low-to-moderate alcohol intake has been linked with reduced all-cause mortality and morbidity, the effect of recent alcohol intake on female reproductive function has not been clearly established. OBJECTIVE: We assessed the relation between acute alcohol consumption, reproductive hormones, and markers of menstrual cycle dysfunction including sporadic anovulation, irregular cycle length, luteal phase deficiency, long menses, and heavy blood loss. DESIGN: A total of 259 healthy, premenopausal women from Western New York were followed for ≤2 menstrual cycles (2005-2007) and provided fasting blood specimens during ≤8 visits/cycle and four 24-h dietary recalls/cycle. Linear mixed models were used to estimate associations between previous day's alcohol intake and hormone concentrations, whereas Poisson regression was used to assess RR of cycle-average alcohol intake and menstrual cycle function. RESULTS: For every alcoholic drink consumed, the geometric mean total and free estradiol, total and free testosterone, and luteinizing hormone were higher by 5.26% (95% CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%), 1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively, after adjustment for age, race, percentage of body fat, perceived stress, pain-medication use, sexual activity, caffeine, and sleep. Binge compared with nonbinge drinking (defined as reporting ≥4 compared with <4 drinks/d, respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53% (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically significant associations were shown between cycle-average alcohol intake and menstrual cycle function. CONCLUSION: Although recent moderate alcohol intake does not appear to have adverse short-term effects on menstrual cycle function, including sporadic anovulation, potential protective and deleterious long-term effects of alterations in reproductive hormones on other chronic diseases warrant additional investigation.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Association between metabolic syndrome and periodontal disease measures in postmenopausal women: the Buffalo OsteoPerio study.

BACKGROUND: The objective of this study is to characterize the association between metabolic syndrome (MetS) and periodontitis in women, for which there is limited evidence. METHODS: Cross-sectional associations between MetS and periodontitis were examined in 657 postmenopausal women aged 50 to 79 years enrolled in a periodontal disease study ancillary to the Women's Health Initiative Observational Study. Whole-mouth measures of alveolar crest height (ACH), clinical attachment level (CAL), probing depth (PD), gingival bleeding, and supragingival plaque and measures to define MetS using National Cholesterol Education Program criteria were from a clinical examination. Study outcomes were defined as: 1) mean ACH ≥3 mm, two sites ≥5 mm, or tooth loss to periodontitis; 2) ≥2 sites with CAL ≥6 mm and ≥1 site with PD ≥5 mm; 3) gingival bleeding at ≥50% of sites; and 4) supragingival plaque at ≥50% of sites. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In unadjusted analyses, MetS (prevalence: 25.6%) was significantly associated with supragingival plaque (OR = 1.74; 95% CI: 1.22 to 2.50) and non-significantly associated with periodontitis defined by ACH (OR = 1.23; 95% CI: 0.81 to 1.85) and gingival bleeding (OR = 1.20; 95% CI: 0.81 to 1.77). Adjustment for age, smoking, and other confounders attenuated observed associations, though supragingival plaque remained significant (OR = 1.47; 95% CI: 1.00 to 2.16; P = 0.049). MetS was not associated with periodontitis defined by CAL and PD. CONCLUSIONS: A consistent association between MetS and measures of periodontitis was not seen in this cohort of postmenopausal women. An association between MetS and supragingival plaque requires further investigation.

Association of prediagnostic physical activity with survival following breast cancer diagnosis: influence of TP53 mutation status.

PURPOSE: Physical activity both before and after breast cancer diagnosis has been associated with improved survival. However, it is not clear whether this association differs by molecular features of the tumor or by recency of the physical activity to the time of diagnosis. METHODS: We examined the association of prediagnostic physical activity with survival in a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer, examining tumor molecular subtypes. Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI). RESULTS: Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. Compared with inactive patients (<3 h/week), women with higher average lifetime physical activity (>6 h/week) had reduced risk of all-cause mortality (adjusted HR = 0.61, 95 % CI 0.40-0.95; p trend =0.04). There were no clear differences in the associations for lifetime and more recent physical activity. Lifetime physical activity was also weakly associated with decreased risk of breast cancer-specific mortality. Higher lifetime physical activity was associated with reduced risk of all-cause mortality among women with ER-positive tumors (HR = 0.52, 95 % CI 0.29-0.93) and mutant TP53 tumors (HR = 0.22, 95 % CI 0.06-0.72); however, no statistically significant interactions were observed for ER or TP53 status. CONCLUSIONS: Our study further supports that prediagnostic physical activity improves overall survival following breast cancer and suggests that the associations of prediagnostic physical activity with survival following breast cancer may vary by molecular features of the tumor, particularly ER and TP53 status.

The association of depressive symptoms and pulmonary function in healthy adults.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.