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.

The prevalence of left ventricular hypertrophy associated with type-2 diabetes in Shiraz, Iran: a cross-sectional study.

BACKGROUND: Left ventricular hypertrophy (LVH) is a common diagnosis in patients with cardiovascular disease (CVD). The prevalence of LVH among patients with Type-2 Diabetes Mellitus (T2DM), high blood pressure and aging is higher than the healthy population and has been independently associated with an increased risk for future cardiac event, including stroke. The aim of this study is to identify the prevalence of LVH among T2DM subjects and evaluate its association with related risk factors of CVD patients in the metropolis of Shiraz, Iran. The novelty of this study is that there has been no known published epidemiological study related to the relationship of LVH and T2DM on this unique population. MATERIALS AND METHOD: This cross-sectional study was designed based on collected data of 7715 free dwelling subjects in the community-based Shiraz Cohort Heart Study (SCHS) from 2015 to 2021, ages 40-70 years. Overall, 1118 subjects with T2DM were identified in the SCHS and after exclusion criteria, 595 subjects remained eligible for study. Subjects with electrocardiography (ECG) results, which are appropriate and diagnostics tools, were evaluated for the presence of LVH. Thus, the variables related to LVH and non-LVH in subjects with diabetes were analyzed using version-22 statistical package for social sciences software program to ensure consistency, accuracy, reliability, and validity for final analysis. Based upon related variables and identifying LVH and non-LVH subjects, the relevant statistical analysis was implemented to ensure its consistency, accuracy, reliability, and validity for final analysis. RESULTS: Overall, the prevalence of diabetic subjects was 14.5% in the SCHS study. Furthermore, the prevalence of hypertension in the study subjects aged 40-70 years was 37.8%. The prevalence of hypertension history in T2DM study subjects for LVH compared to non-LVH was (53.7% vs. 33.7%). The prevalence of LVH among patients with T2DM as the primary target of this study was 20.7%. Analytical findings comparing both LVH and non-LVH subjects who have T2DM identified significance for variables in the older (≥ 60) mean and categorical age group (P < 0.0001), history of hypertension (P < 0.0001), mean and categorical duration of hypertension in years (P < 0.0160), status of controlled versus uncontrolled hypertension level (P < 0.0120), the mean systolic blood pressure (P < 0.0001) as well as mean duration years of T2DM and categorical duration of diabetes in years (< 0.0001 and P < 0.0060), mean fasting blood sugar (< 0.0307) and categorical status of FBS Level (mg/dl): controlled and uncontrolled FBS status of controlled vs. uncontrolled FBS levels P < 0.0020). However, there were no significant findings for gender (P = 0.3112), diastolic blood pressure mean (P = 0.7722) and body mass index (BMI) mean and categorical BMI (P = 0.2888 and P = 0.4080, respectively). CONCLUSION: The prevalence of LVH in the study increases significantly among T2DM patients with hypertension, older age, years of hypertension, years of diabetes, and higher FBS. Thus, given the significant risk of diabetes and CVD, evaluation of LVH through reasonable diagnostic testing with ECG can help reduce the risk of future complications through the development of risk factor modifications and treatments guidelines.

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.

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.

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.

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.

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.

BRCA1 polymorphisms and breast cancer epidemiology in the Western New York exposures and breast cancer (WEB) study.

Results of studies for the association of BRCA1 genotypes and haplotypes with sporadic breast cancer have been inconsistent. Therefore, a candidate single nucleotide polymorphism (SNP) approach was used in a breast cancer case-control study to explore genotypes and haplotypes that have the potential to affect protein functions or levels. In a breast cancer case-control study, genotyping of BRCA1 polymorphisms Q356R, D693N, and E1038G was performed on 1,005 cases and 1,765 controls. Unconditional, polytomous logistic regression and χ(2) -tests were used to examine the associations of breast cancer with genotypes and haplotypes. In addition, interactions between genotype and smoking, benign breast disease, family history of breast cancer, body mass index (BMI), alcohol consumption, and hormonal risk factors, hormone receptor status, and breast cancer pathology were calculated also using logistic regression and χ(2) . Although sporadic breast cancer was not associated with BRCA1 genotypes or haplotypes overall or by menopausal status, there was evidence of an interaction between the E1038G BRCA1 genotype, smoking, and BMI among premenopausal women (P for interaction = 0.01 and 0.045, respectively) and between E1038G and D693N BRCA1 genotypes and hormone therapy use among postmenopausal women (P for interaction = 0.01 and 0.02, respectively). There were no other associations found between BRCA1 genotypes and stage, histological grade, or nuclear grade. However, the D693N SNP was associated with the risk of triple negative breast cancer (odds ratio = 2.31 95% confidence interval 1.08-4.93). The BRCA1 variants studied may play a role in the etiology of triple negative breast cancer and may interact with environmental factors such as hormone therapy or smoking and increase sporadic breast cancer risk.

Social Networks, Social Determinants and Mortality: Western New York Exposures and Breast Cancer (WEB) Study.

BACKGROUND: There are few studies of social support and other social determinants of health after breast cancer (BC) diagnosis and their associations with mortality; results have been inconclusive. Further, it is not known if observed associations are specific to women with BC diagnosis or if associations would be similar among healthy women. METHODS: Women with incident, pathologically confirmed invasive BC, stage I-IV (n = 1012) and healthy frequency age-matched controls (n = 2036), answered a social support questionnaire in prospective follow-up of a population-based case-control study, the Western New York Exposures and Breast Cancer (WEB) Study. At interview, all participants were aged 35-79 years and resident of two counties in Western New York State. Mortality status was ascertained from the National Death Index. Participants were queried regarding the number of their close friends, frequency of seeing them, household size, household income, and marital status. Hazard ratios (HR) and 95% confidence intervals (CI) for BC specific mortality (BC women only) and all-cause mortality were estimated. RESULTS: Lower household income was associated with higher all-cause mortality among women diagnosed with BC (HR 2.48, 95% CI, 1.24-4.97) and similarly among the healthy women (HR 2.63, 95% CI, 1.25-5.53). Number and frequency of seeing friends, marital status, and household size were not associated with mortality, either among BC patients or among healthy women. CONCLUSION: Among both those diagnosed with BC and healthy women, lower income was associated with more than twice the mortality. Marital status, household size, number or frequency of meeting friends were not associated with survival.

Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy.

BACKGROUND: Menopausal hormone therapy (MHT) increases the risk of coronary heart disease (CHD) in older women with elevated low-density lipoprotein (LDLC) levels. The endogenous estrogen receptor antagonist 27-hydroxycholesterol (27OHC) is correlated with LDLC levels and may block the beneficial effects of estrogen on the cardiovascular system. METHODS AND RESULTS: We conducted a nested case-control study in the Women's Health Initiative trials of 350 CHD cases and 813 matched controls to explore potential mediation by 27OHC of the dependence of the CHD risk elevation with MHT on LDLC. Baseline levels of 27OHC were not associated with CHD risk when LDLC was included in the multivariable models. The odds ratio for CHD associated with increased LDLC was 1.15 (95% confidence interval, 1.08-1.23) and was unchanged at 1.14 (95% confidence interval, 1.07-1.22) when 27OHC was added to the model. Baseline 27OHC did not interact with MHT on CHD risk (P=0.81). In contrast, LDLC levels modified the effect of MHT on CHD risk (P for interaction=0.02), and adding 27OHC did not affect this result. With the use of log scales, the effect of MHT on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at ≈3.36 mmol/L (130 mg/dL). CONCLUSIONS: This study found that 27OHC does not independently increase the risk of CHD, does not modify the increased risk of CHD resulting from MHT, and does not mediate the interaction of LDLC with MHT. Measuring blood lipids may aid in counseling individual women about initiating MHT and cardiovascular risk mitigation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association.

A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes.

Alcohol intake over the life course and breast cancer survival in Western New York exposures and breast cancer (WEB) study: quantity and intensity of intake.

Alcohol intake is a risk factor for breast cancer, but the association between alcohol and mortality among breast cancer survivors is poorly understood. We examined the association between alcohol intake from all sources, assessed by cognitive lifetime drinking history, and all-cause and breast cancer mortality among women with breast cancer (N = 1,097) who participated in a population-based case-control study. Vital status was ascertained through 2006 using the National Death Index. Using Cox proportional hazards models, we computed hazard ratios for all-cause and breast cancer mortality in association with alcohol intake. We examined lifetime volume and intensity (drinks per drinking day) of alcohol consumption as well as drinking status during various life periods. Analyses were stratified by menopausal status. After adjustment for total intake, postmenopausal women with consumption of four or more drinks per drinking day over their lifetimes were nearly three times more likely to die from any cause compared to abstainers (HR 2.94, 95 % CI 1.31, 6.62). There was a similar but non-significant association with breast cancer mortality (HR 2.68, 95 % CI 0.94, 7.67). Postmenopausal women who drank one drink or fewer per drinking day between menarche and first birth had a significantly decreased hazard of all-cause (HR 0.54, 95 % CI 0.31, 0.95) and breast cancer mortality (HR 0.27, 95 % CI 0.09, 0.77). Premenopausal breast cancer survival was not associated with drinking intensity. We observed no associations between drinking status or total volume of alcohol intake and breast cancer or all-cause mortality. High-intensity alcohol consumption may be associated with decreased survival in postmenopausal women with breast cancer. Low-intensity alcohol consumption between menarche and first birth may be inversely associated with all-cause and breast cancer mortality; this period may be critical for development of and survival from breast cancer. Intensity of alcohol intake may be a more important factor than absolute volume of intake on survival in women with breast cancer.

Clustering of place of birth for women with breast cancer: differences by tumor characteristics.

PURPOSE: There is increasing evidence that exposures in early life affect breast cancer risk, and that breast cancer etiology differs by tumor subtype. If environmental exposures in early life contribute to risk, it is expected that there would be clustering of women with breast cancer by their place of birth, and that clustering might differ by subtype. We examined spatial associations between place of birth and breast cancer by subtype, using hormone receptor status and molecular profiles of breast tumors. METHODS: Data were drawn from the Western New York Exposures and Breast Cancer study, a population-based case-control study of incident, pathologically confirmed breast cancer (1996-2001) in Erie and Niagara Counties. Included were women born in the study area (579 cases and 931 controls). Clustering of breast cancer subgroups relative to controls was examined by the k-function method in groups stratified by estrogen receptor (ER), progesterone receptor (PR), and HER2 status, and by DNA methylation status and p53 mutation status, and the k-function difference was used to compare relative spatial aggregation and spatial range of the difference between case subgroups and controls. RESULTS: We found a tendency to cluster among ER positive, PR positive, and HER2 negative cases (i.e., luminal A subtype), especially among premenopausal women, but not among the other groups defined by hormonal receptor status, or by either methylation or p53 mutation status. CONCLUSIONS: While our findings cannot rule out clustering of cases by birth place because of shared behaviors related to residence location, they also suggest that early life environmental exposures may affect subsequent breast cancer risk, and that premenopausal breast tumors of the luminal A subtype may be more affected by these early life exposures than other subtypes.

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.

Pregnancy-related characteristics and breast cancer risk.

Breast tissues undergo extensive physiologic changes during pregnancy, which may affect breast carcinogenesis. Gestational hypertension, preeclampsia/eclampsia, gestational diabetes, pregnancy weight gain, and nausea and vomiting (N&V) during pregnancy may be indicative of altered hormonal and metabolic profiles and could impact breast cancer risk. Here, we examined associations between these characteristics of a woman's pregnancy and her subsequent breast cancer risk. Participants were parous women that were recruited to a population-based case-control study (Western New York Exposures and Breast Cancer Study). Cases (n = 960), aged 35-79 years, had incident, primary, histologically confirmed breast cancer. Controls (n = 1,852) were randomly selected from motor vehicle records (< 65 years) or Medicare rolls (≥ 65 years). Women were queried on their lifetime pregnancy experiences. Multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). N&V during pregnancy was inversely associated with breast cancer risk. Relative to those who never experienced N&V, ever experiencing N&V was associated with decreased risk (OR 0.69, 95% CI 0.56-0.84) as were increased N&V severity (p trend < 0.001), longer duration (p trend < 0.01), and larger proportion of affected pregnancies (p trend < 0.0001) among women with ≥ 3 pregnancies. Associations were stronger for more recent pregnancies (< 5 years). Findings did not differ by menopausal status or breast cancer subtype including estrogen receptor and HER2 expression status. Other pregnancy characteristics examined were not associated with risk. We observed strong inverse associations between pregnancy N&V and breast cancer risk. Replication of these findings and exploration of underlying mechanisms could provide important insight into breast cancer etiology and prevention.

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.