Healthy Nonsmoking Women Research Articles

Polymorphic variants of the hOGG1, APEX1, XPD, SOD2, and CAT genes involved in DNA repair processes and antioxidant defense and their association with breast cancer risk.

Breast cancer is one of the leading causes of mortality among women. The most frequently encountered tumors are luminal tumors. Associations of polymorphisms in the hOGG1 (rs1052133), APEX1 (rs1130409), XPD (rs13181), SOD2 (rs4880), and CAT (rs1001179) genes were studied in 313 nonsmoking postmenopausal patients with luminal B subtype breast cancer. The control group consisted of 233 healthy nonsmoking postmenopausal women. Statistically significant associations of the XPD and APEX1 gene polymorphisms with the risk of developing luminal B Her2-negative subtype of breast cancer were observed in a log-additive inheritance model, while the CAT gene polymorphism showed an association in a dominant inheritance model (OR = 1.41; CI 95 %: 1.08-1.85; Padj.= 0.011; OR = 1.39; CI 95 %: 1.07-1.81; Padj = 0.013 и OR = 1.70; CI 95 %: 1.19-2.43; Padj = 0.004, respectively). In the group of elderly women (aged 60-74 years), an association of the CAT gene polymorphism with the risk of developing luminal B subtype of breast cancer was found in a log-additive inheritance model (OR = 1.87; 95 % CI: 1.22-2.85; Padj = 0.0024). Using MDR analysis, the most optimal statistically significant 3-locus model of gene-gene interactions in the development of luminal B Her2-negative subtype breast cancer was found. MDR analysis also showed a close interaction and mutual enhancement of effects between the APEX1 and SOD2 loci and the independence of the effects of these loci from the CAT locus in the formation of luminal B subtype breast cancer.

RESPIRATORY DISEASE ASSOCIATED WITH BIOMASS SMOKE EXPOSURE IN RURAL WOMEN

Objective:The aim of this study was to evaluate the effect of biomass fuel combustion on pulmonary function tests (PFTs) and comparing the PFTs between biomass users and Liquefied petroleum gas (LPG) users. Method: 150 healthy non-smoking women were randomly selected within the age group of 21-50 years for this cross-sectional study. The study group comprised of 75 subjects who used biomass fuel for cooking (Biomass users) and 75 age matched subjects who were not exposed to biomass served as the controls (LPG users). . The anthropometric data i.e., age, height, weight, blood pressure, respiratory rate was noted and the subjects pulmonary functions were evaluated using RMS Medspiror. Result: The lung function parameters were significantly lower in the study group, exposed to biomass fuel than the controls FEV1 (p<0.001); FEV1/FVC (p<0.001) and PEFR (p<0.001), except FVC (p<0.338). The evaluation of PFTs suggested the increased risk to the obstructive type of pulmonary disease in biomass users. Conclusion: The reduction in the pulmonary function in the biomass exposed women could be due to high exposure to biomass pollutants with inadequate ventilation in cooking area leading to chronic pulmonary disease.

Urinary iodine excretion and optimal time point for sampling when estimating 24-h urinary iodine.

Iodine deficiency may cause thyroid dysfunction. The iodine intake in a population is measured by urinary iodine concentration (UIC) in spot samples or 24-h urinary iodine excretion (24UIE). 24UIE is considered the gold standard and may be estimated using an equation including UIC, urinary creatinine concentration, sex and age (e24UIE). The aims of this study were to evaluate the preferable timing of UIC when using this equation and assess the variability of UIE. Sixty healthy non-smoking women (n 31) and men (n 29) were included in Gothenburg, Sweden. Twelve urine samples were collected at six fixed times on two separate days. Variability was calculated for UIC, 24UIE, e24UIE, iodine excretion per hour (iHr) and UIC adjusted for creatinine and specific gravity. Median 24UIE was 156 µg/24 h and the median UIC (all spot samples) was 104 µg/l. UIC (P < 0·001), 24UIE (P = 0·001) and e24UIE (P < 0·001) were significantly higher in men. e24UIE was relatively similar to 24UIE. However, when e24UIE was calculated from UIC in the first void, it was about 15 % lower than 24UIE (P < 0·001). iHr was lowest in the morning and highest in the afternoon. Median iHr was higher in men (7·4 v. 5·3 µg/h, P < 0·001). The variability of UIE was higher within individuals than between individuals. This study suggests that most time points for estimation of individual 24UIE are appropriate, but they should preferably not be collected in the first void.

Serum heavy metals of passive smoker females and its correlation to bone biomarkers and risk of osteoporosis.

Serum total and free calcium reflect the status of the body health and disease. Smoking is risk factor for many diseases as cardiovascular, lung, and cancers. The goal of this work is to evaluate the correlation between serum lead, cadmium arsenate resulting from passive smoking, and bone status in females. This study was conducted on two hundred women (age 30-50 years) divided into four groups (each 50). Group I, control, included non-smoking healthy women. Group II included heavy smoker (>20 cigarettes/day). Group III, nonsmoker women with osteoporosis, have many fractures. Group IV, smoking women with osteoporosis, included heavy smokers (>20 cigarettes/day) with osteoporotic women and have many fractures. Data obtained showed that T-score of osteoporotic smokers was -3.5 that indicated reduced bone mineral density (BMD) while serum total and ionized calcium were statistically significant decreased in smokers with or without osteoporosis compared with nonsmokers (p < 0.001). A negative correlation between total and free calcium and cadmium levels in smokers was compared with nonsmokers (r =-0.65). The levels of C-terminal pro-peptide of pro-collagen type I (PICP) and N-terminal pro-peptide of procollagen type I (PINP) were higher in smoker osteoporotic women than nonsmokers. It was concluded that cadmium resulting from smoking may compete with absorption of calcium and reduced its level and BMD and increased incidence of osteoporosis. The elevated PICP and PINP indicated decreased rate of proto collagen I turnover in bone tissue and increased incidence of osteoporosis.

Study of the Lung Function Tests in Healthy Non-Smoking Women Using Different Cooking Fuels

Background: In developing country like India still a large group of women use biomass as the cookingfuel in a poorly ventilated cooking area and it is considered as a major risk factor for respiratory diseases.Throughthis study we sought to find the effect of biomass and LPG fuel use on the lung function by studspirometry.Method: This cross-sectional study was conducted in the rural and urban areas of Ghaziabad. We assessedthe lung function in 100 non-smoker females (50 biomass and 50 LPG fuel users) and studies the presenceof any correlation between lung function and the duration of exposure.Results: Compared to LPG users biomass fuel users had significantly lower values of FVC (p = 0.007), FEV1(p = 0.0024), FEV1/FVC (p &lt;0.0001) and PEFR (p = 0.007). Statistically significant negative correlationwas also found between exposure index and spirometry values in both the groups.Conclusion: Biomass fuel has a more adverse effect on the lung function and the lung function decline isassociated with the exposure duration.

Effects of smoking cessation on sexual functions and health quality of life in premenopausal women: A prospective case - Controlled study.

To evaluate whether smoking cessation has an effect on female sexual function and quality of life. After approval by the local ethics committee, smoking and non-smoking female participants were included in the study and all participants filled the female sexual function index (FSFI) and the short form 36 (SF-36). The same questionnaires were filled again at the ninth month control after smoking cessation. The scores of these questionnaires were compared between the groups. In addition, the FSFI and SF-36 scores of the participants in the smoking group were also compared with the scores in the ninth month after smoking cessation. The rate of female sexual dysfunction (FSD) was significantly higher in the smoking group when compared with the control group (86.0% vs 32.5%; P<0,001). The FSFI total and sub-domains score was significantly lower in the smoking group when compared control group [21.5 (min:14.4-max:28.69) and 28.9 (min:17.7-max:32.8); P<.001, respectively]. The rate of FSD was significantly decreased after nine months of smoking cessation (86% to 35.1%; P<.001). After smoking cessation, significant improvements on FSFI total and sub-domain scores and SF-36 sub-domain scores were determined. In this study, it was shown that smoking negatively affected FSD and QOL when compared with healthy non-smoking women, and smoking cessation caused significant improvements in FSFI and SF-36 scores in these women after 9months.

Impact of maternal height on birthweight classification in singleton births at term: a cohort study in The Netherlands

Objective To assess the association between maternal height and birthweight in a healthy population and to study the effect of maternal height on the classification of birthweight as small for gestational age (SGA) and large for gestational age (LGA). Methods A descriptive, observational retrospective study was conducted in a low risk population in the Netherlands. The study included term singleton healthy nonsmoking pregnant women with normal body mass index (n = 9291). We calculated the impact of maternal height on birthweight using multiple linear regression analyses with adjustment for gestational age, gender, and parity. We calculated the number of newborns classified as SGA and LGA using the cutoff point of the Dutch Birthweight chart, which does not customize for maternal height. Subsequently, we calculated the changes in classification from SGA and LGA to appropriate for gestational age (AGA) in case of customization for maternal height. Results A significant association was found between maternal height and birthweight; 15.0 g higher birthweight per extra cm maternal height (95% confidence interval 13.8–16.1; p<.001; R 2 model = 0.28). The incidence of SGA was 7.1% (range 17.4–2.0% form shortest to tallest maternal height category) and of LGA 8.4% (range 1.9–21.5% from shortest to tallest maternal height category). We calculated a shift in classification: 114 newborns (17.3%) in shorter (<167 cm) women previously SGA and 165 newborns (21.1%) in taller (>173 cm) women previously LGA were classified as AGA when controlling for maternal height. Conclusions Maternal height is significantly associated with birthweight. Birthweight charts customized for maternal height change classification in one out of six SGA or LGA newborns at term.

Expression of genes involved in inflammation and growth - does sampling site in human full-term placenta matter?

Objective To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy. Methods All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR). Results The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively). Conclusion Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.

Effects of biomass burning on pulmonary functions in tribal women in northeastern India

ABSTRACTWood smoke causes adverse effects on pulmonary function (PF) in women in developing countries. This study compared PF among rural tribal women in northeastern India among 266 wood users and 82 liquefied petroleum gas (LPG) users, all healthy nonsmoking women from April to July, 2014. PF measurements included FVC, FEV1, FEV1/FVC, PEF, and FEF25–75%. Information on participants’ health status, demographic, and socioeconomic characteristics were collected by questionnaire. Multiple linear regressions were performed to compare PF between the two groups, adjusting for potential confounders. Wood users had significantly lower pulmonary values than LPG users: FVC (2.65 vs. 2.85 L, p < .001), FEV1 (1.46 vs. 1.92 L, p < .001), PEF (1.89 vs. 2.56 L/s, p < .001), and FEF25–75% (1.12 vs. 1.68 L/s, p < .001) except for FEV1/FVC (76.5 vs. 75.5 percent, p = .27). Wood use was associated with 7 percent lower FVC, 24 percent lower FEV1, 1.3 percent lower FEV1/FVC, 26 percent lower PEF, and 33 percent lower FEEF25–75% compared to LPG use. Wood use was associated with a 0.27-L decrease in FEV1, adjusted for covariates. Women cooking with wood had lower PF and more respiratory symptoms and gastritis than those using LPG. Thus, reducing indoor air pollution from biomass burning is needed to protect tribal women’s health.

Research Article: Impact of Cooking Fuel Choices on Maternal Lung Functions in Selected Rural and Urban Areas of Copperbelt Province, Zambia

Background: Considering the respiratory health risk of exposure to biomass cooking fuel emissions, this study was conducted to elucidate the relationship between cooking fuel choices and declined pulmonary function in rural and urban population in the Copperbelt Province of Zambia. Methods: We carried out a cross-sectional study of 1,170 healthy nonsmoking pregnant women from Masaiti and Ndola predominantly using biomass fuel for cooking. Questionnaire based data was acquired along with standardized measures of lung function. MIR Spirobank G (Italy) was used in spirometry based on American Thoracic Standards. Results: The present study found that over two thirds (69.2%) of pregnant women in the study population use biomass for cooking and only 12.4 % use electricity only. Declined lung function was found to be statistically significantly associated with cooking fuel choices (p – value 0.005) and a weak association was observed with gravida at a p-value of 0.056. Pregnant women using crop residues as cooking fuel were two times more likely to have a declined lung function [AOR 2.33 (1.27, 4.30)] compared with pregnant women using mixed fuel type (biomass and electricity) and those using electricity only were 57% less likely to have a declined lung function [AOD 0.43 (0.26, 0.69)]. Conclusion: Use of biomass for cooking among pregnant women is a strong determinant of declined lung function. Interventions to improve maternal respiratory health outcomes in Zambia and other countries in sub-Saharan Africa should involve making cleaner cooking fuel energy options available and accessible by ordinary women from both rural and urban areas.

The DAMA trial: a diet and physical activity intervention trial to reduce mammographic breast density in postmenopausal women in Tuscany, Italy. Study protocol and baseline characteristics.

Aims and background. High mammographic breast density (MBD) is an established risk factor for breast cancer (BC). The influence of diet and physical activity (PA) on MBD has long been investigated. In an observational study of a cohort in Florence, we observed inverse associations between consumption of vegetables and olive oil and moderate leisure-time PA and MBD, while high alcohol intake and high glycemic load diets were positively associated with MBD. We set out to investigate whether dietary and PA interventions were able to reduce MBD in postmenopausal women with high MBD (>50%). Methods and study design. The DAMA (Diet, physical Activity and MAmmography) trial, a factorial randomized trial involving healthy nonsmoking postmenopausal women not using hormone replacement therapy and having MBD >50%, is aimed at evaluating the ability of a 24-month intervention based on moderate-intensity PA and/or dietary modification focused on plant foods with a low glycemic load, low in saturated fats and alcohol, and rich in antioxidants and fiber, to reduce the percent MBD. Participants have been randomized to 1 of 4 study arms (diet, PA, diet + PA, control). Dietary and PA habits and anthropometry are collected at baseline and at the end of the intervention phase together with repeated blood and urine samples. The primary outcome of the study is the absolute change in percent MBD as assessed on baseline and follow-up digital mammograms performed in the framework of the local screening program. Results. Of 728 eligible women, 234 (32.1%) agreed to participate. We did not observe any difference across study arms in the baseline distribution of variables of interest related to diet and lifestyle. Conclusions. The DAMA trial may contribute to a better understanding of MBD determinants. This will provide insight into the pathogenesis of BC and may allow the development of strategies for primary prevention focused on high-MBD groups that are easily identifiable in large-scale BC screening programs. ISRCTN28492718.

611: The effects of pre-pregnancy BMI and antenatal weight change on adiopocytokine levels

Numerous adipocytokines are implicated as contributing factors to various perinatal disease states, though data are conflicting. This study aims to determine the influence of pre-pregnancy body mass index (BMI) and antenatal weight changes on the maternal and fetal levels of adiponectin, leptin and resistin, in healthy women. This was a prospective cohort study of healthy non-smoking women without gestational-diabetes, with singleton gestations. Maternal serum was collected between 32-34 weeks, with maternal and cord blood collected at delivery. Plasma adiponectin, leptin and resistin were measured using commercial immunoassays. Cohorts were defined in two modes: BMI <25 vs. ≥25 and gaining ≤ Institute of Medicine (IOM) weight recommendation vs. > IOM recommendations. Analysis performed using T-test with bootstrapping, Chi-square tests and Spearman’s correlations, with generalized linear models to control for confounding. 61% of subjects began pregnancy with a BMI ≥25, of whom 65% exceeded IOM weight gain recommendations. 62% with a BMI<25 exceeded IOM recommendations (P=0.77). There were no significant demographic differences between groups. Leptin levels were significantly higher in maternal and fetal subjects who exceeded IOM recommendations, which persisted after controlling for BMI. Women with a BMI<25 had higher 32-34 week and term adiponectin levels and lower leptin levels, which persisted after controlling for weight change (Table 1). Leptin demonstrated a significant positive correlation with net weight change at 32-24 weeks and term (Table 2). A negative trend between net weight change and term adiponectin levels was noted, with a significant negative correlation between pre-pregnancy BMI and both 32-34 week and term adiponectin levels. A woman’s BMI at conception influences third trimester adiponectin and leptin levels, with a lesser impact on resistin. Exceeding IOM weight gain recommendations (regardless of BMI at conception) effects only leptin levels.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Personal exposure to fine particulate matter and benzo[a]pyrene from indoor air pollution and leukocyte mitochondrial DNA copy number in rural China.

Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal combustion. Previous studies found that increased exposure to PM2.5 and benzo[a]pyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-μg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell [95% confidence interval (95% CI): -18.6, -2.0; P = 0.02]. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.

Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women.

Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21–45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value<0.1). The most significant protein was succinate dehydrogenase subunit C (SDHC), a key enzyme complex of the mitochondrial tricarboxylic acid (TCA) cycle. The other statistically significant proteins (NR2F1, MSI1, MYH1, FOXO1, KHDRBS3, NFKBIE, LYZ and IKZF1) are involved in multiple pathways, including DNA base-pair repair, inflammation and oncogenic pathways. None of the 258 KEGG and 1,139 GO pathways was found to be statistically significant after FDR adjustment. This study suggests several chemopreventive mechanisms of aspirin in humans, which have previously been reported to play a role in anti- or pro-carcinogenesis in cell systems; however, larger, confirmatory studies are needed.

How Does Tobacco Smoke Affect Fetal Growth Potential in the First Trimester of Pregnancy as Measured by Volume Parameters of the Fetus, Trophoblast, and Gestational Sac?

We aimed to assess if tobacco smoke, as measured by the serum concentration of cotinine and blood concentration of cadmium, influences the fetal, sac, and trophoblast volume in the first trimester of pregnancy. We enrolled women in weeks 11 to 14 of pregnancy: 35 smokers, 24 passive smokers, and 98 nonsmoking healthy women. We found that the fetus volume was similar in all groups (18.70 ± 6.29, 17.11 ± 5.4, 18.97 ± 7.55 cm3). The trophoblast was significantly smallest in smokers (50.27 ± 19.56, 56.71 ± 23.50, 61.95 ± 22.94 cm3). The trophoblast volume was correlated with cotinine and cadmium concentration ( r = -0.54, r = -0.44). In passive smokers, gestational sac and trophoblast volume grew systematically and were correlated with the mean parental height. In smokers, only the gestational sac grew systematically and was correlated with the mean parental height. The fetus volume was independent of mean parental height and intensity of exposure to tobacco smoke. Volumetric changes of the fetus, trophoblast, and sac may be observed in the first trimester; however, their consequences require further research.

Abstract 4284: Exploratory plasma proteomic analysis in a randomized cross-over trial of aspirin among healthy individuals

Abstract Background: Long-term use of aspirin is associated with lower colorectal cancer (CRC) incidence; however, the mechanism of the chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Methods: We assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized, double-blinded, placebo-controlled, cross-over trial of 44 healthy non-smoking men and women, aged 21-45 years. Plasma proteomics was analyzed on an antibody microarray with ∼3,000 full-length antibodies, printed in triplicate. Moderated paired t-test was performed on individual antibodies, and gene set analyses were performed for KEGG and GO pathways. Results: Among the 3,387 antibodies, significant differences in plasma protein levels were observed for 267 antibodies (p&amp;lt;0.05), the most significant protein being a transcription-factor regulator belonging to a steroid receptor family and found to be differentially expressed in colon cancer cells. Other significant proteins are involved in multiple oncogenic pathways related to colon tumorigenesis. In the pathway analysis, 4 KEGG (among 138) and 69 GO (among 1,089) pathways were found to be significant (p&amp;lt;0.05), including natural killer (NK) cell-mediated cytotoxicity, butanoate metabolism and Wnt signaling pathways. Pathways that modulate cellular protein binding to steroid receptors were also significantly different between aspirin treatment and placebo (p&amp;lt;0.05). None of the results remained statistically significant after correction for multiple testing. Conclusion: Several proteins and pathways, which have previously been reported as playing a role in colorectal carcinogenesis in vitro were found to be differentially expressed after aspirin treatment vs. placebo in healthy human subjects. This study suggests several chemopreventive mechanisms of aspirin; however, larger, confirmatory studies are needed. Citation Format: Xiaoliang Wang, Yuzheng Zhang, Ali Shojaie, Paul D. Lampe, Lisa Levy, Ulrike Peters, John D. Potter, Emily White, Johanna W. Lampe. Exploratory plasma proteomic analysis in a randomized cross-over trial of aspirin among healthy individuals. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4284.

ANTIBODIES TO BENZO[A]PYRENE, ESTRADIOL AND PROGESTERONE IN THE POSTMENOPAUSAL BREAST CANCER WOMEN

The identification of women who are at high risk of developing breast cancer plays a key role in chemoprevention of breast cancer selective estrogen receptor modulators. purpose: To study specific immune responses to chemical carcinogens and sex steroid hormones associated with breast cancer in postmenopausal women. material and methods. Serum IgA-antibodies specific to benzo[a]pyrene, estradiol and progesterone were studied in 203 non-smoking healthy women and 469 non-smoking breast cancer patients (125 with ER– and 344 with ER+) using semi-quantitative enzyme immunoassay. results. The low levels of all three antibodies were revealed in 53.2 % of healthy donors, in 47.2 % of breast cancer patients with ER– and in 40.7 % of patients with ER+. The high levels of all three antibodies were found in 12.3 %, 18.4 % and 26.5 % of cases, respectively. In the studied groups, the levels of antibodies to estradiol and progesterone were correlated with the levels of antibodies to benzo[a]pyrene (rs=0.54–0.7, p<0.0001). Conclusion. Immunoassay of antibodies to exogenous and endogenous antigens could be useful for determining risk of developing ER+ breast cancer and preventing administration of tamoxifen and others selective modulators of estrogen receptors. Active immunization against exogenous chemical carcinogens could increase the levels of antibodies to endogenous steroids, thus stimulating breast cancer.

Smoking impairs and circulating stem cells favour the protective effect of the T allele of the connexin37 gene in ischemic heart disease – A multinational study

BackgroundThe connexin 37 (Cx37) gene is considered to be a candidate gene for ischemic heart disease (IHD). We analyzed the association between the C1019 > T (Pro319 > Ser) variant of the Cx37 gene and IHD in patients in the Czech Republic, Croatia, Hungary and Romania with regard to the presence/absence of selected cardiovascular risk factors (RF). In a complementary study, we analyzed the association between the Cx37 gene and circulating stem and endothelial progenitor cells in healthy women. MethodsThe study population comprised 2396 patients (663 women) with IHD. The control population comprised 2476 subjects (1, 337 women). Additionally, in 662 healthy women, the association between the Cx37 gene and circulating stem and endothelial progenitor cells was analyzed. ResultsThe strongest protective effect of the Cx37 T allele was detected in non-smoking patients without diabetes mellitus and hypertension (OR 0.610, 95% CI 0.377–0.990); a similar effect was found in non-smoking men (OR 0.781, 95% CI 0.628–0.971); weaker effect was found in non-smoking women (OR 0.768, 95% CI 0.560–1.050). In non-smoking healthy women, stem cells were significantly higher in TT than in CT and CC carriers (p for trend 0.011). Additionally, non-smoking TT carriers had significantly higher number of stem cells than past and current smoking TT carriers (p for trend = 0.006); no such trend was found in CT and CC carriers. ConclusionsThe protective effect of the T allele of the Cx37 gene might be strongly modified by smoking; in women, this effect could be mediated through stem cells.

The effects of Secondhand Smoke (SHS) exposure on microvascular endothelial function among healthy women.

BackgroundStudies have demonstrated that secondhand smoke (SHS) exposure could impair endothelial function. However, the effect of SHS exposure specifically on microvascular endothelial function is not well understood. This study aimed to determine the effects of SHS exposure on microvascular endothelial function among non-smoking, generally healthy women.FindingsWe studied 127 women; and based on their hair nicotine levels measured using gas chromatography-mass spectrometry, 25 of them were categorized as having higher hair nicotine levels, 25 were grouped as having lower hair nicotine and 77 women were grouped into the non-detected group. The non-detected group did not have detectable levels of hair nicotine. Anthropometry, blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured accordingly. Microvascular endothelial function was assessed non-invasively using laser Doppler fluximetry and the process of iontophoresis involving acetylcholine and sodium nitroprusside as endothelium-dependent and endothelium-independent vasodilators respectively. The mean hair nicotine levels for higher and lower hair nicotine groups were 0.74 (1.04) and 0.05 (0.01) ng/mg respectively. There were no significant differences in anthropometry, BP, lipid profile and hsCRP between these groups. There were also no significant differences in the microvascular perfusion and endothelial function between these groups.ConclusionIn this study, generally healthy non-smoking women who have higher, lower and non-detected hair nicotine levels did not show significant differences in their microvascular endothelial function. Low levels of SHS exposure among generally healthy non-smoking women may not significantly impair their microvascular endothelial function.

How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized controlled trial

Controversy surrounds the effectiveness of dietary guidelines for cardiovascular disease (CVD) prevention in healthy middle-aged and older men and women. The objective was to compare effects on vascular and lipid CVD risk factors of following the United Kingdom dietary guidelines with a traditional British diet (control). With the use of a parallel-designed randomized controlled trial in 165 healthy nonsmoking men and women (aged 40-70 y), we measured ambulatory blood pressure (BP) on 5 occasions, vascular function, and CVD risk factors at baseline and during 12 wk after random assignment to treatment. The primary outcomes were differences between treatments in daytime ambulatory systolic BP, flow-mediated dilation, and total cholesterol/HDL cholesterol. Secondary outcomes were differences between treatment in carotid-to-femoral pulse wave velocity, high-sensitivity C-reactive protein, and a measure of insulin sensitivity (Revised Quantitative Insulin Sensitivity Check Index). Data were available on 162 participants, and adherence to the dietary advice was confirmed from dietary records and biomarkers of compliance. In the dietary guidelines group (n = 80) compared with control (n = 82), daytime systolic BP was 4.2 mm Hg (95% CI: 1.7, 6.6 mm Hg; P < 0.001) lower, the treatment effect on flow-mediated dilation [-0.62% (95% CI: -1.48%, 0.24%)] was not significant, the total cholesterol:HDL cholesterol ratio was 0.13 (95% CI: 0, 0.26; P = 0.044) lower, pulse wave velocity was 0.29 m/s (95% CI: 0.07, 0.52 m/s; P = 0.011) lower, high-sensitivity C-reactive protein was 36% (95% CI: 7%, 48%; P = 0.017) lower, the treatment effect on the Revised Quantitative Insulin Sensitivity Check Index [2% (95% CI: -2%, 5%)] was not significant, and body weight was 1.9 kg (95% CI: 1.3, 2.5 kg; P < 0.001) lower. Causal mediated effects analysis based on urinary sodium excretion indicated that sodium reduction explained 2.4 mm Hg (95% CI: 1.0, 3.9 mm Hg) of the fall in blood pressure. Selecting a diet consistent with current dietary guidelines lowers BP and lipids, which would be expected to reduce the risk of CVD by one-third in healthy middle-aged and older men and women. This study is registered at www.isrctn.com as 92382106.