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1.
J Invest Dermatol ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31628929

RESUMO

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease characterized by a type 2 cytokines secreted by T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s). Despite a high degree of heterogeneity, AD is still explained by type 2 immunity, and the role of interleukin (IL)-17A, which is increased in acute, pediatric, or Asian patients with AD, remains poorly understood. Here, we aimed to investigate the role of IL-17A-producing ILC3s, which are unexplored immune cells, in the pathogenesis of AD. We found that the numbers of ILC3s in the skin of AD-induced mice were increased, and that neutralizing IL-17A delayed development of AD. Moreover, adoptive transfer of ILC3s accelerated the symptoms of AD. Mechanically, ILC3s induced IL-33 production by non-immune skin cells, keratinocytes, and fibroblasts, which promoted type 2 immune responses. Because AD has a complex pathophysiology and a broad spectrum of clinical phenotypes, the presence of ILC3s in the skin and their interaction with non-immune skin cells could explain the pathogenesis of cutaneous AD.

2.
EBioMedicine ; 48: 203-211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629678

RESUMO

BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10-4. The associations for four variants reached P < 5 × 10-8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10-8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS. INTERPRETATION: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

3.
Korean J Intern Med ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487770

RESUMO

Background/Aims: A link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations. Methods: The relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged ≥ 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the 2nd, 3rd, and 4th weeks. Results: Seventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM. Conclusions: HSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.

4.
Sci Rep ; 9(1): 12524, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467304

RESUMO

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

5.
PLoS Med ; 16(8): e1002893, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31390370

RESUMO

BACKGROUND: Various risk factors have been associated with epithelial ovarian cancer risk in observational epidemiological studies. However, the causal nature of the risk factors reported, and thus their suitability as effective intervention targets, is unclear given the susceptibility of conventional observational designs to residual confounding and reverse causation. Mendelian randomization (MR) uses genetic variants as proxies for risk factors to strengthen causal inference in observational studies. We used MR to evaluate the association of 12 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) with risk of invasive epithelial ovarian cancer, invasive epithelial ovarian cancer histotypes, and low malignant potential tumours. METHODS AND FINDINGS: Genetic instruments to proxy 12 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) that were robustly (P < 5 × 10-8) and independently associated with each respective risk factor in previously reported genome-wide association studies. These risk factors included genetic liability to 3 factors (endometriosis, polycystic ovary syndrome, type 2 diabetes) scaled to reflect a 50% higher odds liability to disease. We obtained summary statistics for the association of these SNPs with risk of overall and histotype-specific invasive epithelial ovarian cancer (22,406 cases; 40,941 controls) and low malignant potential tumours (3,103 cases; 40,941 controls) from the Ovarian Cancer Association Consortium (OCAC). The OCAC dataset comprises 63 genotyping project/case-control sets with participants of European ancestry recruited from 14 countries (US, Australia, Belarus, Germany, Belgium, Denmark, Finland, Norway, Canada, Poland, UK, Spain, Netherlands, and Sweden). SNPs were combined into multi-allelic inverse-variance-weighted fixed or random effects models to generate effect estimates and 95% confidence intervals (CIs). Three complementary sensitivity analyses were performed to examine violations of MR assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P value threshold was used to establish strong evidence (P < 0.0042) and suggestive evidence (0.0042 < P < 0.05) for associations. In MR analyses, there was strong or suggestive evidence that 2 of the 12 risk factors were associated with invasive epithelial ovarian cancer and 8 of the 12 were associated with 1 or more invasive epithelial ovarian cancer histotypes. There was strong evidence that genetic liability to endometriosis was associated with an increased risk of invasive epithelial ovarian cancer (odds ratio [OR] per 50% higher odds liability: 1.10, 95% CI 1.06-1.15; P = 6.94 × 10-7) and suggestive evidence that lifetime smoking exposure was associated with an increased risk of invasive epithelial ovarian cancer (OR per unit increase in smoking score: 1.36, 95% CI 1.04-1.78; P = 0.02). In analyses examining histotypes and low malignant potential tumours, the strongest associations found were between height and clear cell carcinoma (OR per SD increase: 1.36, 95% CI 1.15-1.61; P = 0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset: 1.09, 95% CI 1.02-1.16; P = 0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per 50% higher odds liability: 0.89, 95% CI 0.82-0.96; P = 0.002). There was little evidence for an association of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone binding globulin with ovarian cancer or its subtypes. The primary limitations of this analysis include the modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the association of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptive use, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk. CONCLUSIONS: Our comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for few of these factors in invasive epithelial ovarian cancer overall and suggests distinct aetiologies across histotypes. The identification of novel risk factors remains an important priority for the prevention of epithelial ovarian cancer.

6.
Diabetes Metab J ; 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31237129

RESUMO

BACKGROUND: The association between change in alcohol intake and metabolic syndrome is unclear. METHODS: This retrospective cohort consisted of 41,368 males and females from the Health Examinees-GEM study. Participants were divided into non-drinkers (0.0 g/day), light drinkers (male: 0.1 to 19.9 g/day; female: 0.1 to 9.9 g/day), moderate drinkers (male: 20.0 to 39.9 g/day; female: 10.0 to 19.9 g/day), and heavy drinkers (male: ≥40.0 g/day; female: ≥20.0 g/day) for each of the initial and follow-up health examinations. Logistic regression analysis was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for developing metabolic syndrome according to the change in alcohol consumption between the initial and follow-up health examinations. Adjusted mean values for the change in waist circumference, fasting serum glucose (FSG), blood pressure, triglycerides, and high density lipoprotein cholesterol (HDL-C) levels were determined according to the change in alcohol consumption by linear regression analysis. RESULTS: Compared to persistent light drinkers, those who increased alcohol intake to heavy levels had elevated risk of metabolic syndrome (aOR, 1.45; 95% CI, 1.09 to 1.92). In contrast, heavy drinkers who became light drinkers had reduced risk of metabolic syndrome (aOR, 0.61; 95% CI, 0.44 to 0.84) compared to persistent heavy drinkers. Increased alcohol consumption was associated with elevated adjusted mean values for waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels (all P<0.05). Reduction in alcohol intake was associated with decreased waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels among initial heavy drinkers (all P<0.05). CONCLUSION: Heavy drinkers who reduce alcohol consumption could benefit from reduced risk of metabolic syndrome.

7.
BMJ Open ; 9(6): e025477, 2019 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-31209083

RESUMO

OBJECTIVES: This study evaluated whether individuals with affected family member adhered to healthy behaviours. DESIGN AND SETTING: This was a cross-sectional study of participants selected from health examinees who underwent the national health check-up programme of Korea in 39 centres between 2004 and 2013. PARTICIPANTS: The baseline data of 128 520 participants enrolled in the Health Examinees-Gem study were used for analysis. MAIN OUTCOMES AND MEASURES: Associations of family history of diabetes with adherence to regular exercise, healthy diet and body composition, and clusters of healthy behaviours were evaluated while adjusting for potential confounders selected by a directed acyclic graph. RESULTS: Participants with a family history of diabetes were more likely to adhere to a regular exercise regimen (OR=1.12, 95% CI 1.06 to 1.18 for men and OR=1.10, 95% CI 1.07 to 1.14 for women) and healthy diet (OR=1.06, 95% CI 1.01 to 1.12 for men and OR=1.06, 95% CI 1.01 to 1.12 for women) but were less likely to have a normal body composition (OR=0.83, 95% CI 0.78 to 0.87 for men and OR=0.83, 95% CI 0.80 to 0.86 for women). These associations were strengthened when the affected family members were siblings, the number of affected members was increased or the age at diagnosis of the affected member was younger than 50 years. In men and women, having a normal body composition is important in determining the cluster of behaviours, and those with a family history of diabetes were less likely to adhere to the normal body composition cluster. CONCLUSIONS: The group with high risk of diabetes showed healthy behaviors, but they did not have a normal body composition. Policies and campaigns targeting integrated health behaviors will be needed to reduce the burden of diseases and improve public health.

8.
Mol Genet Genomic Med ; 7(6): e707, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066241

RESUMO

BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium. METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models. RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537). CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

9.
Sci Rep ; 9(1): 3103, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816310

RESUMO

We aimed to examine the effect of weight change attributable to cessation of cigarette smoking on newly diagnosed metabolic syndrome (MetS). We prospectively followed 5,809 men aged between 40 to 69 years without MetS at baseline in the Health Examinees-Gem (HEXA-G) study up to 4 years. The participants were grouped into continual smokers, quitters with weight gain, quitters without weight change, quitters with weight loss, and never smokers. We constructed multivariable logistic regression models adjusted for sociodemographic factors, health status, and health conditions to estimate the odds of newly diagnosed MetS. During the follow-up, there were 609 cases of newly diagnosed MetS in 5,809 men of the HEXA-G study. After adjustment for potential confounders, the odd ratios (OR) and 95% confidence intervals (95% CI) for MetS were 1.90 (95% CI: 1.43-2.52) in quitters with weight gain, 0.77 (95% CI: 0.60-1.00) in quitters without weight change, and 0.40 (95% CI: 0.28-0.57) in quitters with weight loss compared with continual smokers. Never smokers also had lower odds of MetS (OR = 0.54; 95% CI: 0.42-0.71) compared to continual smokers. Weight management program following smoking cessation may be necessary in clinical practice to reduce worsening of cardiometabolic risk factors related to post-cessation weight gain.

10.
BMJ Open ; 9(3): e021577, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30918027

RESUMO

OBJECTIVE: Several studies identified neighbourhood context as a predictor of prognosis in ischaemic heart disease (IHD). The present study investigates the relationships of neighborhood-level and individual-level socioeconomic status with the odds of ongoing management of IHD, using baseline survey data from the Korea Health Examinees-Gem study. DESIGN: In this cross-sectional study, we estimated the association of the odds of self-reported ongoing management with the neighborhood-level income status and percentage of college graduates after controlling for individual-level covariates using two-level multilevel logistic regression models based on the Markov Chain Monte Carlo function. SETTING: A survey conducted at 17 large general hospitals in major Korean cities and metropolitan areas during 2005-2013. PARTICIPANTS: 2932 adult men and women. OUTCOME MEASURE: The self-reported status of management after incident angina or myocardial infarction. RESULTS: At the neighbourhood level, residence in a higher-income neighbourhood was associated with the self-reported ongoing management of IHD, after controlling for individual-level covariates [OR: 1.22, 95% credible interval (CI): 1.01 to 1.61). At the individual level, higher education was associated with the ongoing IHD management (high school graduation, OR: 1.33, 95% CI: 1.08 to 1.65); college or higher, OR: 1.63, 95% CI: 1.22 to 2.12; reference, middle school graduation or below). CONCLUSIONS: Our study suggests that policies or interventions aimed at improving the quality and availability of medical resources in low-income areas may associate with ongoing IHD management. Moreover, patient-centred education is essential for ongoing IHD management, especially when targeted to patients with IHD with a low education level.

11.
Maturitas ; 121: 76-82, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30704569

RESUMO

A lack of estrogen due to menopause changes metabolic homeostasis, which increases the risk of metabolic syndrome (MetS) in postmenopausal women. Hormone therapy (HT) has beneficial effects on chronic diseases as well as on menopause symptoms. The aim of this study was to investigate the association of HT use with MetS and its components by diabetes status in middle-aged postmenopausal Korean women. A cross-sectional analysis was undertaken of a total of 39,295 non-diabetic and 3,359 diabetic postmenopausal women aged 40 to 69 years from the Health Examinees-Gem (HEXA-G) study (2004-2013). The mean differences in the MetS components by HT use were assessed using a general linear model and Tukey's multiple comparisons tests. The prevalence odds ratio (POR) and 95% confidence intervals (CIs) were estimated using the logistic regression model. HT use was associated with lower fasting glucose level, total cholesterol, systolic blood pressure, body mass index, waist circumference, and waist-to-hip ratio among both diabetic and non-diabetic women. In non-diabetic women, HT 'ever' use was negatively associated with the prevalence of MetS (POR = 0.80, 95% CI: 0.75-0.85), and current users had a lower prevalence of MetS (POR = 0.68, 95% CI: 0.60-0.76). A longer duration of HT use was associated with a decreasing prevalence of MetS. We did not find heterogeneity by age regarding MetS prevalence. Our results suggest that HT use is negatively associated with the prevalence of MetS among postmenopausal women. However, further longitudinal studies are required to investigate the effect of HT on MetS in Korean women.


Assuntos
Diabetes Mellitus/epidemiologia , Terapia de Reposição Hormonal , Síndrome Metabólica/epidemiologia , Pós-Menopausa , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Prevalência , República da Coreia/epidemiologia , Circunferência da Cintura , Relação Cintura-Quadril
12.
J Epidemiol ; 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-30146528

RESUMO

BACKGROUND: We aimed to report the prevalence and correlates of high-risk alcohol consumption and types of alcoholic beverages. METHODS: The baseline data of the Health Examinees-Gem (HEXA-G) study participants, including 43,927 men and 85,897 women enrolled from 2005 through 2013, were used for analysis. Joinpoint regression was performed to estimate trends in the age-standardized prevalence of alcohol consumption. Associations of demographic and behavioral factors, perceived health-related effects, social relationships, and the diagnostic history of diseases with alcohol consumption were assessed using multinomial logistic regression. RESULTS: The prevalence of alcohol consumption remained higher in men during the study period and increased in women. The amount of alcohol consumed has increased in women, especially that from beer and makgeolli, a traditional Korean fermented rice wine. Older participants were less likely to be high-risk drinkers (men and women who drink more than 40 or 20 g/day of alcohol, respectively) and drink Soju, a distilled liquor, and beer, and more likely to drink makgeolli. Educational level was negatively associated with high-risk drinking. However, it was positively associated with the consumption of strong spirits and wine. Smoking was associated with high-risk drinking and the consumption of soju and strong spirits. Engaging in regular exercise and having stress were associated with drinking all types of beverages except for soju. CONCLUSIONS: Sex-specific trends in alcohol consumption were influenced by demographic, behavioral, and perceived health-related factors. The findings will help improve the understanding of alcohol-related problems and provide evidence for establishing country-specific policies and campaigns in Korea.

13.
J Phys Act Health ; 15(10): 763-773, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30124089

RESUMO

BACKGROUND: This study aimed to estimate the prevalence and trends of participation in physical activity (PA) in Korean adults. METHODS: The Korea National Health and Nutrition Examination Survey (KNHANES; 2009-2013) and the Korea Community Health Survey (KCHS; 2009-2013) were used to estimate the prevalence of PA. Age standardization was performed using population projections for Korea in 2005 as a standard population. Trends of the prevalence from 2009 to 2013 were assessed by joinpoint regression analysis. RESULTS: The age-standardized prevalence for achieving the recommended level of PA was 63.0% in KNHANES and 64.5% in KCHS for men, and 53.7% in KNHANES and 56.3% in KCHS for women. Decreasing trends were observed for the prevalence of achieving the recommended level of PA in the KNHANES and KCHS; however, only the trend for women in KNHANES was statistically significant. CONCLUSIONS: Approximately, 60% of adults participate in the recommended level of PA in Korea. The survey design and characteristics should be considered when interpreting the prevalence of PA from different databases.

14.
Pharmacogenomics J ; 18(5): 633-645, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29618765

RESUMO

Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and solute carrier (SLC) genes and cancer survival were investigated through a meta-analysis and an association study in the Seoul Breast Cancer Study (SEBCS). Including the SEBCS, the meta-analysis was conducted among 38 studies of genetic variations of transporters on various cancer survivors. The population of SEBCS consisted of 1338 breast cancer patients who had been treated with adjuvant chemotherapy. A total of 7750 SNPs were selected from 453 ABC and/or SLC genes typed by an Affymetrix 6.0 chip. ABCB1 rs1045642 was associated with poor progression-free survival in a meta-analysis (HR = 1.33, 95% CI: 1.07-1.64). ABCB1, SLC8A1, and SLC12A8 were associated with breast cancer survival in SEBCS (Pgene < 0.05). ABCB1 rs1202172 was differentially associated with survival depending on the chemotherapy (Pinteraction = 0.035). Our finding provides suggestive associations of membrane transporters on cancer survival.

16.
J Prev Med Public Health ; 50(6): 401-410, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29207445

RESUMO

Objectives: The purpose of this study was to examine the associations of childbirth, breastfeeding, and their interaction with breast cancer (BC) risk reduction, and to evaluate the heterogeneity in the BC risk reduction effects of these factors by menopause, hormone receptor (HR) status, and pathological subtype. Methods: BC patients aged 40+ from the Korean Breast Cancer Registry in 2004-2012 and controls from the Health Examinee cohort participants were included in this study after 1:1 matching (12 889 pairs) by age and enrollment year. BC risk according to childbirth, breast-feeding, and their interaction was calculated in logistic regression models using odds ratios (ORs) and 95% confidence intervals (CIs). Results: BC risk decreased with childbirth (3+ childbirths relative to 1 childbirth: OR, 0.66; 95% CI, 0.56 to 0.78 and OR, 0.80; 95% CI, 0.68 to 0.95 in postmenopausal and premenopausal women, respectively); and the degree of risk reduction by the number of children was heterogeneous according to menopausal status (p-heterogeneity=0.04), HR status (p-heterogeneity<0.001), and pathological subtype (p-heterogeneity<0.001); whereas breastfeeding for 1-12 months showed a heterogeneous association with BC risk according to menopausal status, with risk reduction only in premenopausal women (p-heterogeneity<0.05). The combination of 2 more childbirths and breastfeeding for ≥13 months had a much stronger BC risk reduction of 49% (OR, 0.51; 95% CI, 0.45 to 0.58). Conclusions: This study suggests that the combination of longer breastfeeding and more childbirths reduces BC risk more strongly, and that women who experience both 2 or more childbirths and breastfeed for ≥13 months can reduce their BC risk by about 50%.


Assuntos
Aleitamento Materno , Neoplasias da Mama/patologia , Parto , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Índice de Massa Corporal , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Pós-Menopausa , Pré-Menopausa , Receptores Estrogênicos/metabolismo , Sistema de Registros , República da Coreia , Fatores de Risco , Mulheres
17.
Breast Cancer Res ; 19(1): 119, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29116004

RESUMO

BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP. CONCLUSIONS: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , História Reprodutiva , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/etiologia , Adulto Jovem
18.
Cancer Epidemiol ; 50(Pt A): 16-21, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28763723

RESUMO

PURPOSE: To assess the validity of the cohort study participants' self-reported cancer history via data linkage to a cancer registry database. METHODS: We included 143,965 participants from the Health Examinees (HEXA) study recruited between 2004 and 2013 who gave informed consent for record linkage to the Korean Central Cancer Registry (KCCR). The sensitivity and the positive predictive value of self-reported histories of cancer were calculated and 95% confidence intervals were estimated. RESULTS: A total of 4,860 participants who had at least one record in the KCCR were included in the calculation of sensitivity. In addition, 3,671 participants who reported a cancer history at enrollment were included in the calculation of positive predictive value. The overall sensitivity of self-reported cancer history was 72.0%. Breast cancer history among women showed the highest sensitivity (81.2%), whereas the lowest sensitivity was observed for liver cancer (53.7%) and cervical cancer (52.1%). The overall positive predictive value was 81.9%. The highest positive predictive value was observed for thyroid cancer (96.1%) and prostate cancer (96.1%), and the lowest was observed for cervical cancer (43.7%). CONCLUSION: The accuracy of self-reported cancer history varied by cancer site and may not be sufficient to ascertain cancer incidence, especially for cervical and bladder cancers.


Assuntos
Coleta de Dados/métodos , Registros Médicos , Neoplasias/epidemiologia , Sistema de Registros/normas , Autorrelato , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Reprodutibilidade dos Testes , República da Coreia/epidemiologia
19.
PLoS One ; 12(6): e0179094, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28614389

RESUMO

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/fisiologia , Hepatite C Crônica/tratamento farmacológico , Interferon Tipo I/administração & dosagem , Interleucinas/genética , Ribavirina/administração & dosagem , Idoso , Antivirais/farmacologia , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Interferon Tipo I/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Ribavirina/farmacologia , Resultado do Tratamento , Carga Viral
20.
BMC Public Health ; 17(1): 356, 2017 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-28438146

RESUMO

BACKGROUND: Understanding which factors influence participation in physical activity is important to improve the public health. The aim of the present review of reviews was to summarize and present updated evidence on personal and environmental factors associated with physical activity. METHODS: MEDLINE and EMBASE were searched for reviews published up to 31 Jan. 2017 reporting on potential factors of physical activity in adults aged over 18 years. The quality of each review was appraised with the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) checklist. The corrected covered area (CCA) was calculated as a measure of overlap for the primary publications in each review. RESULTS: Twenty-five articles met the inclusion criteria which reviewed 90 personal and 27 environmental factors. The average quality of the studies was moderate, and the CCA ranged from 0 to 4.3%. For personal factors, self-efficacy was shown as the strongest factor for participation in physical activity (7 out of 9). Intention to exercise, outcome expectation, perceived behavioral control and perceived fitness were positively associated with physical activity in more than 3 reviews, while age and bad status of health or fitness were negatively associated with participation in physical activity in more than 3 reviews. For environmental factors, accessibility to facilities, presence of sidewalks, and aesthetics were positively associated with participation in physical activity. CONCLUSIONS: The findings of this review of reviews suggest that some personal and environmental factors were related with participation in physical activity. However, an association of various factors with physical activity could not be established because of the lack of primary studies to build up the organized evidence. More studies with a prospective design should be conducted to understand the potential causes for physical activity.


Assuntos
Exercício , Fatores Etários , Meio Ambiente , Nível de Saúde , Humanos , Aptidão Física , Estudos Prospectivos , Características de Residência , Literatura de Revisão como Assunto , Autoeficácia
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