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1.
Br J Cancer ; 124(4): 842-854, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33495599

RESUMO

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.

2.
Wiad Lek ; 73(10): 2120-2126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33310933

RESUMO

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.


Assuntos
Comportamento Alimentar , Estudantes , Criança , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino , Polônia , Instituições Acadêmicas , Inquéritos e Questionários
3.
Wiad Lek ; 73(9 cz. 2): 1904-1908, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33148832

RESUMO

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.


Assuntos
Comportamento Alimentar , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Acidente Vascular Cerebral/prevenção & controle , Inquéritos e Questionários , Verduras
4.
J Natl Cancer Inst ; 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32785646

RESUMO

BACKGROUND: The aetiology 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 (GWAS) of MBC identified two predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism (SNP) genotyping of European ancestry MBC case subjects and controls, in three stages. Associations between directly genotyped and imputed SNPs with MBC were assessed using fixed-effects meta-analysis of 1,380 cases and 3,620 controls. Replication genotyping of 810 cases and 1,026 controls was used to validate variants with P-values < 1 x 10-06. Genetic correlation with FBC was evaluated using LD 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 (PRS) and MBC. All statistical tests were two-sided. RESULTS: The GWAS identified three novel MBC susceptibility loci that attained genome-wide significance (P < 5 x 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen-receptor (ER) positive FBC. Males in the top quintile of genetic risk had a four-fold 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 x 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic aetiology with FBC and identifying a four-fold high risk group of susceptible men.

5.
Sci Rep ; 10(1): 11762, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678138

RESUMO

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.

6.
Wiad Lek ; 72(9 cz 2): 1740-1746, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31622258

RESUMO

OBJECTIVE: Introduction: Dietary trends such as consumption of lactose-free and gluten-free products or the use of alternative slimming diets are gaining increasing popularity, especially among young people. They determine their dietary choices, which are important from the point of view of human health. Unconventional diets are still considered as effective weight loss methods. The use of alternative diets may cause shortages of an essential nutrients, increase the risk of chronic non-communicable diseases and lead to the formation of incorrect eating habits. Balanced diet, in contrast to the alternative diet, takes into account the principles of rational nutrition and nutritional recommendations of the Institute of Food and Nutrition (IZZ). The aim: To investigate the influence of popular dietary trends on nutrition of high school adolescences. PATIENTS AND METHODS: Material and methods: Subjects were adolescences in the age of 17-21 years attending high schools in Ruda Slaska (262 students, including 157 women and 105 men). Self-constructed questionnaire was applied in the study. Participation in the study was anonymous and voluntary. RESULTS: Results: In more than a half of young women (54,8%) and men (52,4%) the body mass deficiency was revealed (BMI<18 kg/m2). 33,6% of the respondents were on the non-balanced diets at least once in their lives. High school students knew gluten-free and lactose-free products but dietary trends, such as the consumption of gluten-free and lactose-free products, did not affect their diet. The main source of nutritional knowledge among respondents were their friends (78,2%). CONCLUSION: Conclusions: The results of the conducted research indicate the need to implement educational programs on the principles of proper nutrition. The increasing awareness of the youth in this regard may contribute to reducing the interest in still popular alternative diets among young people and taking appropriate health behaviors by them.


Assuntos
Dieta , Preferências Alimentares , Estado Nutricional , Adolescente , Índice de Massa Corporal , Comportamento Alimentar , Feminino , Humanos , Masculino , Estudantes , Inquéritos e Questionários
7.
Clin Epigenetics ; 11(1): 66, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039828

RESUMO

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.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA , Estrogênios/efeitos adversos , Estudo de Associação Genômica Ampla/métodos , Estudos de Casos e Controles , Ilhas de CpG , Metilação de DNA/efeitos dos fármacos , Epigênese Genética , Feminino , Predisposição Genética para Doença , Humanos , Itália , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Wiad Lek ; 72(12 cz 1): 2371-2377, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-32124756

RESUMO

In the population of Poland, as well as in other European countries, an aging process is taking place. It is expected that in Poland in 2050, up to 35% of the population may be seniors. With increasing age, there are numerous changes in the body that necessitate the modification of the current diet. Incorrect diet is a risk factor for many old age diseases, including neurodegenerative diseases, osteoporosis, atherosclerosis, stroke, type 2 diabetes and hypertension. The aim of this study is to review the nutrition recommendations in selected diseases of the elderly. The diet of seniors should provide the right amount of nutrients and be adapted to existing diseases. A proper diet can reduce the risk of complications from senile diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Dieta , Europa (Continente) , Humanos , Estado Nutricional , Polônia
9.
Wiad Lek ; 71(7): 1214-1221, 2018.
Artigo em Polonês | MEDLINE | ID: mdl-30448787

RESUMO

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.


Assuntos
Doenças Cardiovasculares/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Acidente Vascular Cerebral/epidemiologia , Adulto , Feminino , Humanos , Masculino , Polônia , Fatores de Risco , População Rural
10.
Prz Menopauzalny ; 17(2): 101-104, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30150920

RESUMO

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.

11.
Wiad Lek ; 71(2 pt 2): 358-365, 2018.
Artigo em Polonês | MEDLINE | ID: mdl-29786586

RESUMO

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.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar/psicologia , Preferências Alimentares/psicologia , Comportamentos Relacionados com a Saúde , Estado Nutricional , Adolescente , Dieta/psicologia , Feminino , Humanos , Masculino , Polônia , Distribuição por Sexo , Estudantes/estatística & dados numéricos , Adulto Jovem
12.
Arch Med Sci ; 14(2): 415-421, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29593817

RESUMO

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.

13.
Pol Merkur Lekarski ; 43(258): 268-271, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29298966

RESUMO

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.


Assuntos
Acromegalia/etiologia , Adenoma/complicações , Infertilidade Feminina/etiologia , Neoplasias Hipofisárias/complicações , Acromegalia/complicações , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Adenoma/diagnóstico , Adenoma/cirurgia , Adulto , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/cirurgia , Hipófise/cirurgia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Gravidez , Resultado do Tratamento
14.
Acta Biochim Pol ; 63(4): 737-744, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27741327

RESUMO

RNAComposer is a fully automated, web-interfaced system for RNA 3D structure prediction, freely available at http://rnacomposer.cs.put.poznan.pl/ and http://rnacomposer.ibch.poznan.pl/. Its main components are: manually curated database of RNA 3D structure elements, highly efficient computational engine and user-friendly web application. In this paper, we demonstrate how the latest additions to the system allow the user to significantly affect the process of 3D model composition on several computational levels. Although in general our method is based on the knowledge of secondary structure topology, currently the RNAComposer offers a choice of six incorporated programs for secondary structure prediction. It also allows to apply a conditional search in the database of 3D structure elements and introduce user-provided elements into the final 3D model. This new functionality contributes to a significant improvement of the predicted 3D model reliability and it facilitates a better model adjustment to the experimental data. This is exemplified based on the RNAComposer application for modelling of the 3D structures of precursors of the miR160 family members.


Assuntos
MicroRNAs/química , Software , Animais , Sequência de Bases , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico , Análise de Sequência de RNA
15.
Fertil Steril ; 105(6): 1511-1518.e3, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26921623

RESUMO

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.


Assuntos
Intoxicação por Metais Pesados , Envenenamento/metabolismo , Envenenamento/patologia , Fumar/metabolismo , Fumar/patologia , Útero/metabolismo , Útero/patologia , Adulto , Endométrio/metabolismo , Endométrio/patologia , Feminino , Humanos , Metais Pesados/metabolismo , Pessoa de Meia-Idade , Oligoelementos/análise , Oligoelementos/metabolismo , Útero/química
16.
Ginekol Pol ; 86(7): 504-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26376527

RESUMO

OBJECTIVES: Beta-agonists play an important role in tocolytic treatment. In light of recent changes in the Polish medical care system, we decided to assess the effectiveness of oral continuous treatment (in 2012) and compare it with a 3-day intravenous administration of fenoterol (in 2013). The aim of our study was to contrast cost and effectiveness of fenoterol therapy in pregnant women at risk of preterm labor during two consecutive years: 2012 - when fenoterol had been widely used (group A), and 2013 when its extensive use had been withdrawn (group B). MATERIAL AND METHODS: Retrospective cohort study of 129 pregnant women: 76 treated with intravenous fenoterol, followed by continuous oral administration (November 2012; group A), and 53 treated with intravenous fenoterol only for 48-72 hours (November 2013; group B). RESULTS: Perinatal outcomes (based on the Apgar score and neonatal weight) were comparable in both groups. Continuous oral application of fenoterol resulted in earlier gestational age at delivery and lower cost of hospitalization among women from group A as compared to group B. Regardless, the difference was not statistically significant (37 hbd vs. 35 hbd, p = 0.626; 4334,700PLN vs. 5232,470PLN, p = 0.533). CONCLUSIONS: A 3-day intravenous application of fenoterol is as effective as oral continuous therapy and is characterized by reduced risk of negative side effects.


Assuntos
Fenoterol/uso terapêutico , Trabalho de Parto Prematuro/tratamento farmacológico , Resultado da Gravidez , Tocólise/métodos , Tocolíticos/uso terapêutico , Centros Médicos Acadêmicos , Adulto , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/prevenção & controle , Polônia , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Clin Epigenetics ; 7: 67, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26244061

RESUMO

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.

18.
Ann Agric Environ Med ; 22(2): 259-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26094520

RESUMO

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.


Assuntos
Poluentes Ambientais/toxicidade , Genitália Feminina/efeitos dos fármacos , Metais Pesados/toxicidade , Reprodução/efeitos dos fármacos , Animais , Cádmio/toxicidade , Cricetinae , Feminino , Intoxicação por Metais Pesados , Humanos , Chumbo/toxicidade , Mercúrio/toxicidade , Camundongos , Envenenamento , Ratos
19.
Cancer Res ; 75(14): 2844-50, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25977328

RESUMO

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.


Assuntos
Células Sanguíneas/metabolismo , Neoplasias da Mama/genética , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Lesões Pré-Cancerosas/genética , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/sangue , Fatores de Risco
20.
Cancer Epidemiol Biomarkers Prev ; 24(1): 221-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25371448

RESUMO

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.


Assuntos
Metilação de DNA/genética , Estudo de Associação Genômica Ampla/métodos , Leucócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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