Incorporation of Anions into Anodic Alumina-A New Track in Cr(VI) Anodizing Substitution?

Aluminum technical alloys are well known for their outstanding mechanical properties, especially after heat treatment. However, quenching and aging, which improve the mechanical properties, by the formation of Cu-rich zones and phases that are coherent with the matrix and block the dislocation motion, cause uneven distribution of the elements in the alloy and consequently make it prone to corrosion. One method providing satisfactory corrosion protection of aluminum alloys is anodizing. On an industrial scale, it is usually carried out in electrolytes containing chromates that were found to be cancerogenic and toxic. Therefore, much effort has been undertaken to find substitutions. Currently, there are many Cr(VI)-free substitutes like tartaric-sulfuric acid anodizing or citric-sulfuric acid anodizing. Despite using such approaches even on the industrial scale, Cr(VI)-based anodizing still seems to be superior; therefore, there is an urge to find more complex but more effective approaches in anodizing. The incorporation of anions into anodic alumina from the electrolytes is a commonly known effect. Researchers used this phenomenon to entrap various other anions and organic compounds into anodic alumina to change their properties. In this review paper, the impact of the incorporation of various corrosion inhibitors into anodic alumina on the corrosion performance of the alloys is discussed. It is shown that Mo compounds are promising, especially when combined with organic acids.

Quality of Life of Women with Polycystic Ovary Syndrome.

Background and Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by multiple hormonal and metabolic abnormalities, including insulin resistance, hyperandrogenism, and disturbances in lipid and carbohydrate metabolism. The objective of this study is to assess the quality of life of women diagnosed with polycystic ovary syndrome (PCOS) and to identify any factors within the study group that may impact the scores related to quality of life. Materials and Methods: This research was carried out among women diagnosed with PCOS. An original questionnaire, developed through an online Google Forms survey, was utilized as the research instrument and distributed through social networks and support groups to women facing PCOS. This study encompassed a participant pool of 200 women with PCOS, aged 24 years or older. For the analytical component, Pearson's χ2 test was employed-a nonparametric test designed to assess the relationship between two variables measured on a qualitative scale. The chosen level of statistical significance was set at p < 0.05. Results: The analysis revealed that the quality of life of the women under study was not linked to the duration of the disease or comorbidities. However, a significant association was observed with the inconvenience caused by PCOS symptoms. Women experiencing very bothersome symptoms of PCOS reported a lower quality of life compared to those with symptoms rated as not very bothersome. Despite the majority of women with PCOS rating their quality of life as good or very good, they often find the associated symptoms of PCOS bothersome. Women reporting lower quality of life tend to acknowledge the impact of PCOS on their lives, experience a sense of lack of control over the disease, struggle with depression, and do not accept their physical appearance. Conclusions: Hence, the support from specialists like endocrinologists, gynecologists, and nutritionists becomes crucial for many women dealing with PCOS. Adopting a healthy lifestyle, incorporating a balanced diet, and engaging in regular physical activity can assist in managing the troublesome symptoms of PCOS, thereby enhancing overall quality of life. In instances of emotional difficulties, seeking psychological support is equally important, and the significance of support and acceptance from loved ones should not be overlooked.

Canonical analysis of concentrations of toxic metals in endometrium of women with gynecological disorders.

OBJECTIVES: Among the main adverse environmental factors, we usually distinguish the impact of heavy metals, especially Cd and Pb. Apart from the carcinogenic and toxic properties, their potential, stimulating estrogen receptors effect (metaloestrogens) is strongly emphasized; as well as participation in gene regulation mechanisms (epigenetic). The aim of this study is to examine if there is a special scheme of concentrations of heavy metals accumulated in the female endometrium in certain pathologies: endometrial hyperplasia, endometrial cancer, endometrial polyps and miscarriages. The control group consisted of patients with abnormal uterine bleeding or functional bleeding with correct histopathological findings. MATERIAL AND METHODS: The study was performed on 92 women. Microwave induced plasma atomic emission spectrometry was used to assess metals concentrations in tissue material and the results of obtained concentrations were converted to µg/kg. The calculations were performed using discriminant and canonical analyses and revealed four discriminant functions. RESULTS: The results showed that metal's tissue concentrations vary in different types of histopathological diagnosis and the scheme of concentrations might be characteristic for analyzed diagnosis. Pb and Al has the most substantial impact on discrimination. CONCLUSIONS: Endometrium may accumulate toxic metals such as: Pb, Cd, Ni, Mn, Cu, Zn, Al, Cr. It can be assumed that there are characteristic distributions of toxic metals concentrations for individual histopathological diagnoses.

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

BACKGROUND: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. METHODS: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. RESULTS: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8). CONCLUSIONS: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.

Common Susceptibility Loci for Male Breast Cancer.

BACKGROUND: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. RESULTS: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.

ASSOCIATION BETWEEN EATING HABITS AND PHYSICAL ACTIVITY IN PRIMARY SCHOOL STUDENTS.

OBJECTIVE: The aim: The study aimed to assess the association between the physical activity level and eating habits of primary school students. PATIENTS AND METHODS: Material and methods: 139 children attending one of the Polish primary school or football school were included. The research tool was author's anonymous survey. RESULTS: Results: The high physical activity level was observed in 34.1% of boys and in 8.8% of girls. As the level of physical activity increased, the consumption of vegetables and fruits also increased. Whole grain bread, coarse-grained groats, whole grain pasta and brown rice were more popular among students with a high physical activity level. The greater the physical activity, the greater the amount of water drank by students. The consumption of sweets, fast food, and ready-made meals, such as frozen pizza or Chinese soup, decreased with increased physical activity. The choice of healthier substitutes for unhealthy snacks was declared by students with moderate or high physical activity level. There was no correlation between BMI and age and the physical activity level. Girls were less active than boys. CONCLUSION: Conclusions: More active physically children had better eating habits and were more aware of healthy eating principles than less active people.

ASSESSMENT OF ADULT EATING HABITS IN THE NUTRITIONAL PREVENTION OF STROKE.

OBJECTIVE: Introduction: Lifestyle modification, including changing eating habits, plays an essential role in the prevention of stroke. The aim: The study aimed to assess the nutritional prevention of cerebrovascular diseases in adult inhabitants of Poland. PATIENTS AND METHODS: Material and Methods: The study was conducted using the author's questionnaire among 145 women and 76 men, aged 18 - 30 (53.9%) and 50 - 70 (46.1%) years. RESULTS: Results: The following stroke risk factors were found in the examined group: overweight or obesity (46.6%), lack of regular physical activity (48%), smoking (33%), hypertension (22.1%), dyslipidemia (8.6%), diabetes (5.9%), and cardiac arrhythmias (6.3%). The younger subjects compared to older ones more often declared the daily consumption of whole-grain cereal products and vegetables, fish at least once a week, and they preferred vegetable oils. On the other hand, older subjects declared the consumption of sweets, sweet drinks, salt, and fast food less frequently than younger ones. Also, fruits were more often chosen by older people. Both groups declared similar moderate consumption of milk and dairy products with reduced fat content, lean meat, and alcohol. Only 38% of respondents considered their eating habits to be appropriate. CONCLUSION: Conclusions: The eating habits of examined adults only partially met the recommendations regarding the nutritional prevention of stroke. In some elements, younger people were more likely to follow appropriate dietary recommendations, while older people were more appropriate in others. The education regarding the principles of the nutritional prevention of cerebrovascular diseases is still necessary and should be age-appropriate.

DNA methylation of the long intergenic noncoding RNA 299 gene in triple-negative breast cancer: results from a prospective study.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with a high rate of recurrence and poor prognosis. Recently we identified a hypermethylation in the long noncoding RNA 299 (LINC00299) gene in blood-derived DNA from TNBC patients compared with healthy controls implying that LINC00299 hypermethylation may serve as a circulating biomarker for TNBC. In the present study, we investigated whether LINC00299 methylation is associated with TNBC in a prospective nested breast cancer case-control study within the Generations Study. Methylation at cg06588802 in LINC00299 was measured in 154 TNBC cases and 159 breast cancer-free matched controls using MethyLight droplet digital PCR. To assess the association between methylation level and TNBC risk, logistic regression was used to calculate odd ratios and 95% confidence intervals, adjusted for smoking status. We found no evidence for association between methylation levels and TNBC overall (P = 0.062). Subgroup analysis according to age at diagnosis and age at blood draw revealed increased methylation levels in TNBC cases compared with controls in the young age groups [age 26-52 (P = 0.0025) and age 22-46 (P = 0.001), respectively]. Our results suggest a potential association of LINC00299 hypermethylation with TNBC in young women.

Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.

BACKGROUND: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. METHODS: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. RESULTS: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10-12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_vs_Q1 = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. CONCLUSION: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.

[Knowledge on cardiovascular risk factors and symptoms of stroke among inhabitants of rural communite].

OBJECTIVE: Introduction: Stroke is one of the leading causes of mortality and disability in the world. A wide knowledge of risk factors for cerebrovascular diseases is one of the main elements of primary prevention, while knowledge of stroke symptoms can significantly speed up treatment and reduce negative health effects. The aim: To assess the knowledge about stroke and risk factors of cerebrovascular diseases among the inhabitants of the randomly selected rural community (in Lodz Province). PATIENTS AND METHODS: Material and methods: The study included 143 adult residents of Rzasnia. The research was carried out using a self-constructed questionnaire, prepared on the basis of available literature. RESULTS: Results: The average score obtained from the knowledge survey on stroke was 5.79 +/- 3.47 (maximum number of points - 14). The average number of points in people with a family history of stroke was statistically significantly higher (7.46±3.31) than in those with no stroke in the family (4.20±2.98 ) (p <0.001). There was no statistically significant difference between the average number of points and gender (women - 6.13±3.55 points, men - 5.64±3.55, NS) and age (R = -0.1, NS ). However, the positive correlation between educational level and the score obtained in our questionnaire was found (R =0.4, p <0.05). The average number of correctly listed risk factors was: 0.6 ± 1.6. At least one risk factor was reported by only 34% of respondents. Respondents most often mentioned: excessive alcohol consumption (18%), smoking (18%), hypertension (14%), atherosclerosis (11%). The average number of correctly listed symptoms of stroke was: 1.2±1.3. At least one symptom of stroke was reported by only 58% of respondents. The respondents most often reported: headache (29%), speech disorders (22%), gait disturbances (13%), and sensory disorders (13%). If a stroke was suspected, the majority of respondents would call an ambulance (94%). CONCLUSION: Conclusions: Knowledge of the residents of the chosen rural commune about the stroke is not satisfactory and should be supplemented with an educational program that would include as many people as possible.

Uterine rupture at 28 weeks of gestation after laparoscopic myomectomy - a case report.

There are many reasons for sterility, and uterine malformations are of the greatest concern. Among uterine disorders, myomas play a significant role and are present in 27% of infertile women. The occurrence of myomas is frequent - 20-40% in women of reproductive age. Thus, for those infertile patients surgical treatment may be needed to preserve an opportunity to conceive. This case report refers to an uterine rupture at 28 weeks of gestation after laparoscopic myomectomy (3 months before conceiving). The myomectomy was conducted correctly and two layers of sutures on the myometrium were performed. The purpose of the myomectomy in a young woman should be well considered. In cases of infertility, removal of the lesions is usually necessary to give the patient a chance of pregnancy. At the same time, the risk of uterine rupture is increased. There are some suggestions referring to myomectomy to reduce the risk of uterine rupture in a subsequent pregnancy. It seems that the method of sewing the uterine closure is crucial. For example, multilayer uterine stitches, preservation of the endometrial cavity, and avoidance of using electrosurgery to prevent devascularization (to avoid haematoma formation) should be taken into consideration to prevent weakness of the wall of the uterus. Uterine scars differ histologically and biochemically.

[Eating habits of the youth from Ruda Slaska].

OBJECTIVE: Introduction: In recent years, interests on dietary and health food have grown considerably. Nutritional knowledge and eating habits determined in the youth have an impact on the health condition in adulthood. The aim: To evaluate the eating habits in the population of young people from Silesian province. PATIENTS AND METHODS: Materials and methods: The anonymous questionnaire survey was conducted in the group of high school students aged 17-21 years coming from Silesian province, randomly chosen from high schools in Ruda Slaska. The study group consisted of 262 students, 157 (59,9%) women and 105 (40,1%) men. The student`s participation in the study was voluntary. RESULTS: Results: The analysis showed that as many as 40% of high school students never eat regularly and eating of regular meals reported only 11,5%. Less than a half (46,9%) of participants eat breakfast every day. The most commonly consumed meals was lunch (n = 217; 82,8%) and dinner (n = 143; 54,6%). The vast majority of students (77,5%) didn't know the correct classification of the feeding pyramid floors. Moreover, in more than a half of young women (54,8%) and men (52,4%) the body mass deficiency was revealed (BMI<18kg/m2). CONCLUSION: Conclusions: The study showed abnormal nutritional behavior of high school youth. Therefore, there is a need to conduct activities under health prevention, which improve the eating habits of young people.

Identification of toxic metals in human embryonic tissues.

INTRODUCTION: The cause of a significant number of miscarriages remains unexplained. There is a need to identify the potential role of environmental, dietary and lifestyle factors in the risk of pregnancy loss. The present study was the first to investigate the content of miscarried embryonic material with respect to eight metals (aluminium, cadmium, chromium, copper, manganese, nickel, lead and zinc). MATERIAL AND METHODS: Embryonic tissue samples (n = 20) were obtained from women undergoing misoprostol-induced removal of the embryo between the 6th and 9th week of gestation. The content of metals was analyzed using microwave-induced nitrogen plasma atomic emission spectrometry. Based on a short questionnaire, the smoking habits, dietary patterns and place of living of the investigated women were determined. RESULTS: The general mean content of metals (µg/g) decreased in the order copper (33.9) > manganese (24.7) > chromium (13.6) > zinc (13.3) > aluminium (6.5) > nickel (3.0) > lead (2.9) > cadmium (2.5). Profoundly increased concentrations (p < 0.05) of the toxic elements aluminium (over 5-fold), cadmium (over 2-fold) and lead (over 2-fold) were observed in samples obtained from former smoking women. The miscarried material in urban populations also revealed higher levels of cadmium (over 1.5-fold) and lead (over 2-fold) compared to that obtained from women living in rural areas (p < 0.05). No associations with age or diet were found (p > 0.05). CONCLUSIONS: This study identified increased levels of aluminum, cadmium and lead in miscarried embryonic material and suggests some causative factors.

Pregnancy in a woman with acromegaly after transsphenoidal partial resection of pituitary macroadenoma - a case report.

Acromegaly is a systemic disease caused by an excessive release of growth hormone and the hypopituitarism, which is induced by macroadenoma local mass effect. The gynecological and obstetric disorders include irregular menstrual cycles, anovulatory cycles and infertility. Therefore, pregnancy in patients affected by the disease is rare. A CASE REPORT: Patient described in this study became pregnant after pharmacological, surgical and infertility treatment. Hence, the following paper presents the course of pregnancy and the discussion of the impact of acromegaly on female fertility, pregnancy, and concerns related to the diagnosis and treatment.

Metal accumulation in the human uterus varies by pathology and smoking status.

OBJECTIVE: To evaluate the content of Al, Cd, Cr, Cu, Mn, Ni, Pb, and Zn in human endometrium (END), endocervix (ECX), and endometrial (END-P) and endocervical (ECX-P) polyps in relation to histologic image and female demographic characteristics and habits. DESIGN: Tissues were collected during curettage of the uterine cavity, subjected to histopathologic examination, digested, and analyzed with the use of a microwave induced nitrogen plasma atomic emission spectrometer. Demographic/lifestyle characteristics were assessed with the use of a questionnaire. SETTING: University hospital and research laboratory. PATIENT(S): One hundred nine white Polish women undergoing curettage of the END (n = 60) or ECX (n = 23) or dissection of END-P (n = 16) or ECX-P (n = 10). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Trace element concentrations in collected tissues. RESULT(S): Histologic states of analyzed END included: normal (n = 22), irregularity (n = 3), polypoid (n = 12), simple hyperplasia (n = 10), leiomyoma (n = 5), and cancer (n = 8); whereas for ECX: normal (n = 10), inflammation (n = 8), irregularity (n = 2), and cervical intraepithelial neoplasia (CIN; n = 3). All elements were identified in the sampled material. Compared with histologically normal tissues, endometrial cancer, hyperplasia, and CIN revealed significantly increased levels of toxic metals (Cd and Pb), altered status of Cu and Mn, and an elevated Cu/Zn ratio. Current and former smoking was associated with significantly higher Cd and Pb levels in investigated tissues. Polyps represented significant accumulators of Al, Cd, Ni, and Pb (END-P) or Al, Cd, and Cu (ECX-P). CONCLUSION(S): The findings of this study are important in understanding the presence and role of metals in the female reproductive system and its pathology.

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis.

BACKGROUND: Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean ß values over all probes were calculated as a measurement for epigenome-wide methylation. RESULTS: In EPIC, we found that high epigenome-wide methylation was associated with lower risk of breast cancer (odds ratio (OR) per 1 SD = 0.61, 95 % confidence interval (CI) 0.47-0.80; -0.2 % average difference in epigenome-wide methylation for cases and controls). Specifically, this was observed in gene bodies (OR = 0.51, 95 % CI 0.38-0.69) but not in gene promoters (OR = 0.92, 95 % CI 0.64-1.32). The association was not replicated in NOWAC (OR = 1.03 95 % CI 0.81-1.30). The reasons for heterogeneity across studies are unclear. However, data from the BGS cohort was consistent with epigenome-wide hypomethylation in breast cancer cases across the overlapping 450k probe sites (difference in average epigenome-wide methylation in case and control DNA pools = -0.2 %). CONCLUSIONS: We conclude that epigenome-wide hypomethylation of DNA from pre-diagnostic blood samples may be predictive of breast cancer risk and may thus be useful as a clinical biomarker.

Impact of heavy metals on the female reproductive system.

INTRODUCTION: It has been recognized that environmental pollution can affect the quality of health of the human population. Heavy metals are among the group of highly emitted contaminants and their adverse effect of living organisms has been widely studied in recent decades. Lifestyle and quality of the ambient environment are among these factors which can mainly contribute to the heavy metals exposure in humans. OBJECTIVE: A review of literature linking heavy metals and the female reproductive system and description of the possible associations with emission and exposure of heavy metals and impairments of female reproductive system according to current knowledge. RESULTS: The potential health disorders caused by chronic or acute heavy metals toxicity include immunodeficiency, osteoporosis, neurodegeneration and organ failures. Potential linkages of heavy metals concentration found in different human organs and blood with oestrogen-dependent diseases such as breast cancer, endometrial cancer, endometriosis and spontaneous abortions, as well as pre-term deliveries, stillbirths and hypotrophy, have also been reported. CONCLUSIONS: Environmental deterioration can lead to the elevated risk of human exposure to heavy metals, and consequently, health implications including disturbances in reproduction. It is therefore important to continue the investigations on metal-induced mechanisms of fertility impairment on the genetic, epigenetic and biochemical level.

Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer.

Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC) has been associated with the risk of developing several tumor types. Here we evaluate sources of variation of this biomarker and its association with breast cancer risk in a prospective cohort study. mtDNA copy number was measured using quantitative real-time PCR on PBC DNA samples from participants in the UK-based Breakthrough Generations Study. Temporal and assay variation was evaluated in a serial study of 91 women, with two blood samples collected approximately 6-years apart. Then, associations with breast cancer risk factors and risk were evaluated in 1,108 cases and 1,099 controls using a nested case-control design. In the serial study, mtDNA copy number showed low assay variation but large temporal variation [assay intraclass correlation coefficient (ICC), 79.3%-87.9%; temporal ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger age at blood collection, being premenopausal, having an older age at menopause, and never taking HRT, both in cases and controls. Based on measurements in a single blood sample taken on average 6 years before diagnosis, higher mtDNA copy number was associated with increased breast cancer risk [OR (95% CI) for highest versus lowest quartile, 1.37 (1.02-1.83); P trend = 0.007]. In conclusion, mtDNA copy number is associated with breast cancer risk and represents a promising biomarker for risk assessment. The relatively large temporal variation should be taken into account in future analyses.

Temporal stability and determinants of white blood cell DNA methylation in the breakthrough generations study.

BACKGROUND: Epigenome-wide association studies (EWAS) using measurements of blood DNA methylation are performed to identify associations of methylation changes with environmental and lifestyle exposures and disease risk. However, little is known about the variation of methylation markers in the population and their stability over time, both important factors in the design and interpretation of EWAS. We aimed to identify stable variable methylated probes (VMP), i.e., markers that are variable in the population, yet stable over time. METHODS: We estimated the intraclass correlation coefficient (ICC) for each probe on the Illumina 450K methylation array in paired samples collected approximately 6 years apart from 92 participants in the Breakthrough Generations Study. We also evaluated relationships with age, reproductive and hormonal history, weight, alcohol intake, and smoking. RESULTS: Approximately 17% of probes had an ICC > 0.50 and were considered stable VMPs (stable-VMPs). Stable-VMPs were enriched for probes located in "shores" bordering CpG islands, and at approximately 1.3 kb downstream from the transcription start site in the transition between the unmethylated promoter and methylated gene body. Both cross-sectional and longitudinal data analyses provided strong evidence for associations between changes in methylation levels and aging. Smoking-related probes at 2q37.1 and AHRR were stable-VMPs and related to time since quitting. We also observed associations between methylation and weight changes. CONCLUSION: Our results provide support for the use of white blood cell DNA methylation as a biomarker of exposure in EWAS. IMPACT: Larger studies, preferably with repeated measures over time, will be required to establish associations between specific probes and exposures.