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.

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.

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.

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.

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.

Magnitude of the Quality Assurance, Quality Control, and Testing in the Shiraz Cohort Heart Study.

To determine the conclusive integrity in the Shiraz Cohort Heart Study (SCHS) project, management began quality assurance (QA) and quality control (QC) of the collected data throughout the study end-points. The QA is a focused process that prevents and detects data collection errors and verification of intended requirements in the SCHS. The QC is a subset of QA intended to capture errors in processing data through testing and preventive processes to identify problems, defects, or intended requirements. SCHS involved 10,000 males and females aged 40-70 over a 10-year follow-up period with cardiovascular diseases (CVDs) in the city of Shiraz, Iran. The study measured events and access to preventive care in Shiraz city. The SCHS identified unique barriers to select national study models in developing standardized measures related to variations in ethnicity, religion, cross-cultural considerations, and others. A suggested response to this problem was to develop a mechanism to standardize elements of the questionnaire, study design, and method of administration. This action was based on the geographically normal distribution of the Family Physician Health and Medical Services in Shiraz. Important QA and QC decisions were developed and adopted in the construction of the SCHS and follow-up to ensure conclusive integrity.

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.

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.

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.

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.

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.

Depression and body mass index, differences by education: Evidence from a population-based study of adult women in the U.S. Buffalo-Niagara region.

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

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.