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1.
Breast Cancer Res ; 26(1): 139, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350230

RESUMO

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.


Assuntos
Densidade da Mama , Neoplasias da Mama , Mamografia , História Reprodutiva , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Transversais , Mamografia/métodos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/etiologia , Fatores de Risco , Idoso de 80 Anos ou mais , Paridade , Índice de Massa Corporal , Aleitamento Materno , Gravidez , Glândulas Mamárias Humanas/anormalidades , Glândulas Mamárias Humanas/diagnóstico por imagem
2.
Breast Cancer Res ; 24(1): 49, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836268

RESUMO

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.


Assuntos
Densidade da Mama , Neoplasias da Mama , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos Transversais , Feminino , Humanos , Mamografia/métodos , Menarca , Grupos Populacionais , Gravidez , Fatores de Risco
3.
J Sports Sci ; 37(14): 1655-1662, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30836829

RESUMO

Genetic factors are known to influence sport performance. The aim of the present study was to assess genetic variants in genes coding for proteins potentially modulating activity of brain emotion centres in a group of 621 elite athletes (212 endurance, 183 power and 226 combat athletes) and 672 sedentary controls. Ten statistically significant variants were identified in genes encoding elements of serotoninergic, catecholaminergic and hypothalamic-pituitary-adrenal systems in different sport groups. Of those the rs860573 variant in the FEV gene coding for transcription factor exclusively expressed in neurons of the central serotonin system is the only one whose frequency significantly differentiates all the groups of athletes studied, regardless of discipline, from the controls (p = 0.000026). Our results support the hypothesis that genetic variants potentially affecting mental processes and emotions, particularly in the serotonergic pathway, also influence the predispositions to athletic performance.


Assuntos
Desempenho Atlético/fisiologia , Emoções/fisiologia , Polimorfismo de Nucleotídeo Único , Receptores de Serotonina/genética , Adulto , Ansiedade/genética , Proteínas de Ligação a DNA/genética , Feminino , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Proteínas Nucleares/genética , Sistema Hipófise-Suprarrenal/fisiologia , Polônia , Receptor 5-HT1B de Serotonina/genética , Receptor 5-HT2C de Serotonina/genética , Receptores de Catecolaminas/genética , Estresse Psicológico/genética , Fatores de Transcrição , Adulto Jovem
4.
Int J Mol Sci ; 20(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739444

RESUMO

Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian genes in BC risk, 16 functional SNPs were genotyped in 321 BC patients and 364 healthy women using the TaqMan fluorescence-labelled probes or High-Resolution Melt Curve technique in the Real-Time PCR system. The selected SNPs were analyzed for the risk of BC, progression, and the influence on gene expression in BC tissue pairs to demonstrate the functionality of genetic variants. The study showed a relationship between an increased BC risk under the dominant genetic model of CRY2 rs10838524, PER2 rs934945, and recessive genetic model of PER1 rs2735611. A protective effect of BMAL1 rs2279287 was observed among carriers with at least one variant allele. Moreover, we found an increased risk of estrogen-/progesterone-positive tumors under the dominant genetic model of PER2 rs934945 and estrogen negative tumors under the variant genotype of CRY2 rs10838524, PER1 rs2735611. We demonstrated significantly altered gene expression of BMAL1, CRY2, PER1, PER2, PER3 according to particular genotypes in the BC tissue pairs. Our findings support the hypothesized role of circadian genes in breast carcinogenesis and indicate probable biomarkers for breast cancer susceptibility.


Assuntos
Neoplasias da Mama/genética , Ritmo Circadiano/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Genótipo , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances
5.
Med Pr ; 69(4): 439-455, 2018 Aug 20.
Artigo em Polonês | MEDLINE | ID: mdl-30038434

RESUMO

Periodical medical examinations are mandatory for employees in Poland. This rule makes a unique opportunity during occupational health services for implementation of prophylactic activities focused on early diagnosis of various diseases, including cancers. Epidemiological data about cancers is alarming and what is more, further increase in development of cancers is being predicted in population overall. The highest incidence of cancers in the case of Polish women belongs to breast cancer (21.7% of diagnosed cancers in general), while the morbidity rate for uterine cancer, ovarian cancer and cervical cancer amounts to 7.4%, 4.7% and 3.5%, respectively. The aim of this study was to elaborate an algorithm of prophylactic activities integrated with the occupational healthcare system, based on medical literature review and guidelines concerning prophylaxis of selected cancers. Polish cancers' prophylaxis programs related to risk factors were presented in this publication and practical indications for occupational healthcare physicians were worked out. Med Pr 2018;69(4):439-455.


Assuntos
Neoplasias/prevenção & controle , Serviços de Saúde do Trabalhador , Prevenção Primária , Adulto , Idoso , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
6.
PLoS Med ; 14(6): e1002335, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28666001

RESUMO

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction.


Assuntos
Envelhecimento , Densidade da Mama , Perimenopausa , Pós-Menopausa , Pré-Menopausa , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade
7.
Breast Cancer Res ; 18(1): 130, 2016 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-27993168

RESUMO

BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types. METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences. RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p < 0.001). Conversion equations revealed differences converged to zero with increasing dense area. MD differences between screen-film and processed digital on the subsequent screening round were consistent with expected time-related MD declines. CONCLUSIONS: MD was slightly higher when measured on processed than on raw direct digital mammograms. Comparisons of MD on these image formats should ideally control for this non-constant and reader-specific difference.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Processamento de Imagem Assistida por Computador , Mamografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade
8.
Nat Genet ; 39(3): 352-8, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17293864

RESUMO

The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.


Assuntos
Neoplasias da Mama/genética , Caspase 8/genética , Predisposição Genética para Doença , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Variação Genética , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
9.
BMC Cancer ; 15: 657, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26446998

RESUMO

BACKGROUND: Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer. METHODS: We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry. RESULTS: Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype). CONCLUSIONS: GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos , Polimorfismo de Nucleotídeo Único , Adulto , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Ativação Enzimática , Feminino , Genes BRCA1 , Humanos , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Estresse Oxidativo , Fatores de Risco , Selenoproteínas/genética , Selenoproteínas/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Glutationa Peroxidase GPX1
10.
Cancer Causes Control ; 25(12): 1587-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25189422

RESUMO

PURPOSE: Concerns regarding a possible link between bisphenol A (BPA) and breast cancer have been mounting, but studies in human populations are lacking. We evaluated the association between the major urinary BPA metabolite [BPA-glucuronide (BPA-G)] and postmenopausal breast cancer risk in a large population-based case-control study conducted in two cities in Poland (2000-2003); we further explored the association of BPA-G levels with known postmenopausal breast cancer risk factors in our control population. METHODS: We analyzed creatinine-adjusted urinary BPA-G levels among 575 postmenopausal cases matched on age and study site to 575 controls without breast cancer using a recently developed assay. Odds ratios and 95 % confidence intervals were used to estimate the association between urinary BPA-G level and breast cancer using conditional logistic regression. Among controls, geometric mean BPA-G levels were compared across categories of breast cancer risk factors using linear regression models. RESULTS: There was no indication that increased BPA-G was associated with postmenopausal breast cancer (p-trend = 0.59). Among controls, mean BPA-G was higher among women reporting extended use of menopausal hormones, a prior screening mammogram, and residence in Warsaw. Other comparisons across strata of postmenopausal breast cancer risk factors were not related to differences in BPA-G. CONCLUSIONS: Urinary BPA-G, measured at the time of diagnosis, is not linked to postmenopausal breast cancer.


Assuntos
Compostos Benzidrílicos/urina , Neoplasias da Mama/epidemiologia , Glucuronídeos/urina , Fenóis/urina , Adulto , Idoso , Neoplasias da Mama/urina , Estudos de Casos e Controles , Cidades , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Polônia/epidemiologia , Pós-Menopausa , Fatores de Risco , Adulto Jovem
11.
Breast Cancer Res Treat ; 137(3): 837-47, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23271326

RESUMO

Molecular and morphological alterations related to carcinogenesis have been found in terminal duct lobular units (TDLUs), the microscopic structures from which most breast cancer precursors and cancers develop, and therefore, analysis of these structures may reveal early changes in breast carcinogenesis and etiologic heterogeneity. Accordingly, we evaluated relationships of breast cancer risk factors and tumor pathology to estrogen receptor (ER) and progesterone receptor (PR) expression in TDLUs surrounding breast cancers. We analyzed 270 breast cancer cases included in a population-based breast cancer case-control study conducted in Poland. TDLUs were mapped in relation to breast cancer: within the same block as the tumor (TDLU-T), proximal to tumor (TDLU-PT), or distant from (TDLU-DT). ER/PR was quantitated using image analysis of immunohistochemically stained TDLUs prepared as tissue microarrays. In surgical specimens containing ER-positive breast cancers, ER and PR levels were significantly higher in breast cancer cells than in normal TDLUs, and higher in TDLU-T than in TDLU-DT or TDLU-PT, which showed similar results. Analyses combining DT-/PT TDLUs within subjects demonstrated that ER levels were significantly lower in premenopausal women versus postmenopausal women (odds ratio [OR] = 0.38, 95 % confidence interval [CI] = 0.19, 0.76, P = 0.0064) and among recent or current menopausal hormone therapy users compared with never users (OR = 0.14, 95 % CI = 0.046-0.43, P (trend) = 0.0006). Compared with premenopausal women, TDLUs of postmenopausal women showed lower levels of PR (OR = 0.90, 95 % CI = 0.83-0.97, P (trend) = 0.007). ER and PR expression in TDLUs was associated with epidermal growth factor receptor (EGFR) expression in invasive tumors (P = 0.019 for ER and P = 0.03 for PR), but not with other tumor features. Our data suggest that TDLUs near breast cancers reflect field effects, whereas those at a distance demonstrate influences of breast cancer risk factors on at-risk breast tissue. Analyses of mapped TDLUs may provide information about the sequence of molecular changes occurring in breast carcinogenesis.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Glândulas Mamárias Humanas/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Invasividade Neoplásica , Fatores de Risco
12.
Nature ; 447(7148): 1087-93, 2007 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-17529967

RESUMO

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Genoma Humano/genética , Alelos , Proteínas Reguladoras de Apoptose , Sudeste Asiático , Austrália , Estudos de Casos e Controles , Europa (Continente)/etnologia , Feminino , Genótipo , Proteínas de Grupo de Alta Mobilidade , Humanos , MAP Quinase Quinase Quinase 1/genética , Proteínas dos Microfilamentos/genética , América do Norte , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptores de Progesterona/genética , Transativadores
13.
Int Arch Occup Environ Health ; 86(8): 923-30, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23179107

RESUMO

PURPOSE: Light-at-night exposure can disrupt the human circadian rhythm via clock gene expressions. The circadian rhythm influences antioxidant enzymes' activity and cellular mRNA levels of these enzymes. The employees working based on a shift system adjust to the changes occurring both on the cell level and on the level of the whole organism. Therefore, a question should be answered whether shift work disturbs oxidant-antioxidant balance and/or generates oxidative stress. METHODS: A cross-sectional study was conducted among nurses selected from the Local Registry of the Chamber of Nurses and Midwives in Lodz: 359 nurses worked daily only and 349 working rotating night shifts. These two groups differed significantly in respect of age (p < 0.0001), menopausal status (p < 0.0001), and current smoking habit (p = 0.02). The average total work duration was significantly shorter (12.4 years) in nurses working currently rotating night shifts who worked significantly longer on night shifts than day-workers (26.6 years). RESULTS: We found statistically significant higher red blood cell glutathione peroxidase in nurses working on night shifts (21.0 ± 4.6 vs. 20.0 ± 5.0 U/g Hb, p < 0.009) after adjusting for age, oral contraceptive hormone use, smoking, and drinking alcohol during last 24 h. Statistically significant lower vitamin A and E levels were found in the premenopausal women working in rotating system (0.690 ± 0.238 vs. 0.786 ± 0.262 µg/ml, p < 0.0001 for vitamin A and 10.93 ± 4.15 vs. 12.78 ± 4.75 µg/ml, p < 0.0001 for vitamin E). The marker of lipid peroxidation (TBARS concentration) was significantly lower in the premenopausal nurses than postmenopausal ones working day shifts only (2.06 ± 0.76 vs. 2.21 ± 0.80 nmol/ml, p < 0.038). We observed that erythrocyte GSH-Px activity rose statistically significant in nurses working more night shifts per month (p < 0.01). CONCLUSIONS: The results quoted above seem to support the existence of an association between light-at-night exposure and blood glutathione peroxidase activity in female shift workers. Nevertheless, in order to explain the mechanisms of this association, we need more studies.


Assuntos
Antioxidantes/metabolismo , Enfermagem , Exposição Ocupacional , Tolerância ao Trabalho Programado/fisiologia , Carga de Trabalho , Adulto , Ritmo Circadiano , Estudos Transversais , Eritrócitos/enzimologia , Feminino , Glutationa Peroxidase/sangue , Humanos , Luz , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Selênio/sangue , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina A/sangue , Vitamina E/sangue
14.
Med Pr ; 64(3): 397-418, 2013.
Artigo em Polonês | MEDLINE | ID: mdl-24261252

RESUMO

Night shift work has been thought to play a role in the etiology of chronic diseases through a disruption of the circadian rhythm, decreased synthesis of melatonin and sleep deprivation. Our aim was to review the epidemiological studies on the association between night shift work and some pathologies in nurses and midwives. We reviewed publications available in the MEDLINE database and published before June 2012, describing the cross-sectional (almost two thirds of all papers) and cohort studies. In total, we identified 26 original papers, including 5 epidemiological studies addressing diseases or disorders of the digestive system, 3--metabolic syndrome, 2--type 2 diabetes, 9--cardiovascular diseases and (CVD risk factors, 5--obesity/overweight, 2--menstrual disorders and 3--poor pregnancy outcomes. The analysis of the literature indicates that night shift work of nurses and midwives is most strongly associated with a higher risk ofobesity/overweight. In each of the five studies, which we identified this association was observed (confirmed by the statistical significance of the results), also after adjustment for confounders. The results for type 2 diabetes and disorders of the menstrual cycle are also suggestive. Epidemiological data on the other disorders or pathologies discussed in this article seem to be less certain - their results are inconsistent or their number is too small to draw definite conclusions. Further epidemiological studies of nurses and midwives working on night shifts and prospective observations in particular are recommended to find out whether potential association between the night work and discussed health issues is causal.


Assuntos
Nível de Saúde , Tocologia , Enfermeiras e Enfermeiros , Doenças Profissionais/etiologia , Tolerância ao Trabalho Programado/fisiologia , Adulto , Ritmo Circadiano/fisiologia , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Obesidade/etiologia , Gravidez
15.
Med Pr ; 64(2): 245-57, 2013.
Artigo em Polonês | MEDLINE | ID: mdl-23829069

RESUMO

Prolactin - a hormone secreted in a circadian rhythm acts as a regulator of growth and development of the mammary glands. It has been observed that working at night increases breast cancer risk in women. Night shift work, probably carcinogenic to humans (Group 2A IARC), can disrupt a circadian rhythm, and thus potentially alter the rhythm of prolactin secretion. The aim of our work was to review epidemiological evidence on the association between prolactin and the risk of breast cancer and the influence of work at night on prolactin secretion. Search was done in the Medline database by keywords (shift work, work at night, risk of breast cancer and prolactin). 'The increased proliferation of breast cells activated by prolactin can promote the development of cancer. The results of the largest epidemiological prospective studies suggest the association between prolactin levels and the risk of breast cancer in women. So far, only seven studies have investigated the association between work at night and prolactin secretion. In three studies lower concentrations of prolactin have been observed in night shift workers. No relationship between the night shift work duration and prolactin level in women have been reported. Night shift work can modify the profile of prolactin secretion in night workers, probably decreasing the secretion of this hormone at night. It is therefore unlikely that prolactin plays an important role in the development of breast cancer in women working at night. This conclusion is based on the results of a few epidemiological studies.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/fisiopatologia , Ritmo Circadiano , Prolactina/metabolismo , Tolerância ao Trabalho Programado , Feminino , Humanos , Melatonina/metabolismo , Estudos Prospectivos , Risco
17.
J Biol Rhythms ; 38(1): 98-108, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36367167

RESUMO

Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.


Assuntos
COVID-19 , ChAdOx1 nCoV-19 , Adulto , Feminino , Humanos , Masculino , Anticorpos Antivirais , Ritmo Circadiano , Imunoglobulina G , SARS-CoV-2 , Adulto Jovem , Pessoa de Meia-Idade , Idoso
18.
Breast Cancer Res ; 14(2): R64, 2012 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-22513288

RESUMO

INTRODUCTION: Involution of terminal duct lobular units (TDLUs), the structures that give rise to most breast cancers, has been associated with reduced breast cancer risk. Data suggest that the etiology and pathogenesis of luminal A and core basal phenotype (CBP) breast cancers differ, but associations with TDLU involution are unknown. Accordingly, we performed a masked microscopic assessment of TDLU involution in benign tissues associated with luminal A and CBP breast cancers diagnosed among women less than age 55 years. METHODS: Cases were participants in a population-based case-control study conducted in Poland. Increased TDLU involution was defined as fewer acini per TDLU or shorter TDLU diameter. Luminal A was defined as estrogen receptor (ER) positive and/or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 (HER2) negative and CBP as negative for ER, PR, and HER2 with expression of basal cytokeratins or epidermal growth factor receptor (EGFR). We performed logistic regression to evaluate associations between TDLU involution and tumor subtypes, adjusted for clinical characteristics and breast cancer risk factors. RESULTS: Among 232 luminal A and 49 CBP cancers associated with evaluable TDLUs, CBP tumors were associated with significantly greater average number of acini per TDLU (odds ratio (OR) = 3.36, 95% confidence interval (CI) = 1.36 to 8.32, P = 0.009) and larger average TDLU diameter (OR = 2.49, 95% CI = 1.08 to 5.74, P = 0.03; comparing highest to lowest group, adjusted for age and study site). CONCLUSIONS: We suggest that TDLU involution is less marked in benign tissues surrounding CBP as compared to luminal A cancers, which may reflect differences in the etiology and pathogenesis of these tumor subtypes.


Assuntos
Neoplasias da Mama/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Receptores ErbB/metabolismo , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
19.
Hum Genet ; 131(3): 479-90, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21959381

RESUMO

In the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) genome-wide association study of breast cancer, a single nucleotide polymorphism (SNP) marker, rs999737, in the 14q24.1 interval, was associated with breast cancer risk. In order to fine map this region, we imputed a 3.93 MB region flanking rs999737 for Stages 1 and 2 of the CGEMS study (5,692 cases, 5,576 controls) using the combined reference panels of the HapMap 3 and the 1000 Genomes Project. Single-marker association testing and variable-sized sliding-window haplotype analysis were performed, and for both analyses the initial tagging SNP rs999737 retained the strongest association with breast cancer risk. Investigation of contiguous regions did not reveal evidence for an additional independent signal. Therefore, we conclude that rs999737 is an optimal tag SNP for common variants in the 14q24.1 region and thus narrow the candidate variants that should be investigated in follow-up laboratory evaluation.


Assuntos
Neoplasias da Mama/genética , Cromossomos Humanos Par 14 , Estudos de Casos e Controles , Mapeamento Cromossômico/métodos , Feminino , Predisposição Genética para Doença , Projeto HapMap , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
20.
Breast Cancer Res Treat ; 134(3): 1279-90, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22752209

RESUMO

Epidemiologic studies suggest that physical activity reduces breast cancer risk by 20-40 %. However, prior studies have relied on measures of self-report. In a population-based case-control study, we evaluated accelerometer measures of active and sedentary behavior in relation to breast cancer among 996 incident cases and 1,164 controls, residents of Warsaw, Poland (2000-2003), who were asked to wear an accelerometer for 7 days. Accelerometer values were averaged across valid wear days and summarized as overall activity (counts [ct]/min/day); in minutes spent in sedentary behavior (0-99 ct/min); and light (100-759 ct/min) and moderate-to-vigorous (760+ ct/min) activity. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression. Comparing women in the highest quartile (Q4) of activity to those in the lowest (Q1), time spent in moderate-to-vigorous activity was inversely associated with breast cancer odds after adjustment for known risk factors, sedentary behavior and wear time (OR(Q4vsQ1) 0.39, 95 % CI 0.27-0.56; P-trend < .0001). Sedentary time was positively associated with breast cancer, independent of moderate-to-vigorous activity (OR(Q4vsQ1) 1.81, 95 % CI 1.26-2.60; P-trend = 0.001). Light activity was not associated with breast cancer in multivariable models including both moderate-to-vigorous activity and sedentary behavior. Our findings support an inverse association between accelerometer-based measures of moderate-to-vigorous physical activity and breast cancer while also suggesting potential increases in risk with sedentary time.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Exercício Físico , Comportamento Sedentário , Acelerometria/instrumentação , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Polônia/epidemiologia , Fatores de Risco
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