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1.
Medicine (Baltimore) ; 100(6): e24745, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578625

RESUMO

ABSTRACT: Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment.


Assuntos
Neoplasias Pulmonares/mortalidade , Abandono do Hábito de Fumar/estatística & dados numéricos , Idoso , Institutos de Câncer , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia
2.
Sci Rep ; 11(1): 1842, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469114

RESUMO

Several studies have evaluated the association between serum adiponectin levels and knee and hand osteoarthritis (OA); mixed results have been reported. We investigated the relationship between OA and serum adiponectin levels according to the radiographic features of knee and hand OA. A total of 2402 subjects was recruited from the Dong-gu Study. Baseline characteristics were collected via a questionnaire, and X-rays of knee and hand joints were scored using a semi-quantitative grading system. The relationship between serum adiponectin levels and radiographic severity was evaluated by linear and logistic regression analysis. Subjects in the higher serum adiponectin levels tertiles were older and had a lower body mass index (BMI) than those in the lower tertiles. Regarding knee joint scores, serum adiponectin levels was positively associated with the total (P < 0.001), osteophyte (P = 0.003), and joint space narrowing (JSN) scores (P < 0.001) after adjustment for age, sex, BMI, smoking, alcohol consumption, education, and physical activity. In terms of hand joint scores, no association was found between serum adiponectin levels and the total, osteophyte, JSN, subchondral cyst, sclerosis, erosion, or malalignment score after the above-mentioned adjustments. Similarly, subjects with serum adiponectin levels above the median had higher total radiographic scores in the knee joints, but not in the hand joints, after adjustment. An increased serum adiponectin levels was associated with a higher radiographic score in the knee joint, but not in the hand joint, suggesting the involvement of different pathophysiologic mechanisms in the development of OA between those joints.

3.
Maturitas ; 143: 178-183, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33308626

RESUMO

OBJECTIVE: To assess the associations among the estimated glomerular filtration rate (eGFR), albumin to creatinine ratio (ACR), and all-cause and CVD mortality rate and to compare the performances of eGFRMDRD, eGFRCKD-EPI, and eGFRcys using receiver operating characteristic (ROC) analysis in Korean adults aged ≥ 50 years. METHODS: Of the 9,260 subjects who participated in the baseline survey of a prospective longitudinal study conducted in Korea, 9,009 (men: 3,574 (39.7%); women: 5,435 (60.3%)) were included in this analysis after the exclusion of 217 subjects with missing eGFR and 34 subjects with missing ACR data. MAIN OUTCOME MEASURE: The associations of eGFR and ACR with all-cause and CVD mortality were investigated using Cox proportional hazards models that included sex, age, waist circumference, smoking, alcohol intake, degree of physical activity, hypertension, diabetes, systolic blood pressure, log-HbA1c, total cholesterol, log-triglyceride, log-HDL and log-ACR or eGFR. RESULTS: After adjustment for covariates, independent associations were found between all-cause mortality and the eGFRcys (mL/min per 1.73 m2) [HR 1.23, 95% confidence interval (CI) 1.05-1.43 for 60-89 vs. ≥ 90; HR 1.87, 95% CI 1.49-2.34 for 45-59 vs. ≥ 90; HR 2.38, 95% CI 1.77-3.20 for 30-44 vs. ≥ 90; HR 2.82, 95% CI 1.89-4.23 for <30 vs. ≥ 90] and ACR (µg/mg creatinine) [HR 1.09, 95% CI 0.88-1.34 for Q2 vs. Q1; HR 1.34, 95% CI 1.10-1.63 for Q3 vs. Q1; HR 1.49, 95% CI 1.22-1.81 for Q4 vs. Q1]. In addition, independent associations of CVD mortality with the eGFRcys and ACR were significant. In the comparison of eGFR performance, the ROC-plot AUC for all-cause mortality was significantly greater for the eGFRcys than for the eGFRMDRD and eGFRCKD-EPI. CONCLUSION: The eGFRcys and ACR were associated independently with all-cause and CVD mortality after adjustment for covariates, including the eGFRcys and ACR. In addition, the ROC-plot AUC for all-cause mortality was greater for the eGFRcys than for the eGFRMDRD and eGFRCKD-EPI in Korean adults aged ≥ 50 years.


Assuntos
Albuminúria/mortalidade , Doenças Cardiovasculares/mortalidade , Taxa de Filtração Glomerular , Idoso , Idoso de 80 Anos ou mais , Albuminúria/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Cistatina C , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
4.
Artigo em Inglês | MEDLINE | ID: mdl-33318029

RESUMO

BACKGROUND: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. METHODS: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). RESULTS: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively). CONCLUSIONS: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. IMPACT: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

5.
BMC Med ; 18(1): 396, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33327948

RESUMO

BACKGROUND: Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. METHODS: We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. RESULTS: In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. CONCLUSIONS: Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.

6.
Contemp Clin Trials Commun ; 19: 100633, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32885089

RESUMO

Purpose: This study describes the protocol for the design and evaluation of a self-assessment based educational program supporting cancer patients' return-to-work (RTW), prior to its complete and ongoing implementation. Methods: We designed a multi-center, randomized controlled trial with three follow-up points. The study population (N = 239) includes recently diagnosed cancer patients who plan to receive active treatment at two university hospitals in Korea. A pre-test is conducted at the point of enrollment for both groups. The intervention group receives a leaflet clarifying misconceptions about RTW and is shown a video clip of patient interviews concerning RTW. The control group receives a booklet about cancer and nutrition, and is not provided with further intervention. After active treatment, the intervention group receives a one-time, face-to-face education session with an oncology nurse. Following the education session, both groups receive three follow-up phone calls. The first follow-up call occurs at the end of intervention and at the end of active treatment for intervention and control groups, respectively. The next two follow-up calls will be conducted one month and a year following the post-test. The primary outcome is whether the patient has RTW or has plans to RTW, and the secondary outcome is knowledge of RTW. Results: As of April 2020, 239 patients have been enrolled in the trial. Statistical analyses will be conducted upon trial completion in December 2020. Discussion: We hypothesize that the provision of RTW education near diagnosis will not only enhance patients' intentions to RTW, but also effectively encourage them to RTW.

7.
J Korean Med Sci ; 35(17): e148, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32356421

RESUMO

The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 (ALDH2) polymorphism. Therefore, we investigated the relationship between the ALDH2 rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The ALDH2 rs671 genotype was classified as inactive ALDH2 (GG) or active ALDH2 (GA/AA). The risk of gastric cancer was higher in men with the inactive ALDH2 than in those with active ALDH2 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.39), whereas no significant association was found between ALDH2 genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99-1.02). In men, the association between ALDH2 genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive ALDH2 and high risk of gastric cancer.

8.
J Korean Med Sci ; 35(9): e14, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32141245

RESUMO

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes. METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed. RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91-1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15-1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women. CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.

9.
Nat Commun ; 11(1): 1217, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139696

RESUMO

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10-8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Predisposição Genética para Doença , Feminino , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Receptores Estrogênicos/metabolismo , Fatores de Risco
10.
Pathobiology ; 87(3): 179-192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32088722

RESUMO

OBJECTIVES: B7-H3 and B7-H4 proteins are expressed in breast cancer tissues, but their relationships with respect to tumor immune surveillance and outcomes in breast cancer are not conclusive. METHODS: We first examined B7-H3 and B7-H4 mRNA expression in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Next, mRNA and protein expression were assessed by RNAscope in situ hybridization (ISH) and immunohistochemistry in 10 pairs of breast cancer and matched normal tissues. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed in tissue microarray slides containing 198 breast cancer samples. Association of B7-H3 and B7-H4 expression with survival was verified using the publicly accessible BreastMark tool. RESULTS: B7-H3 and B7-H4 mRNA expression were significantly higher in breast cancer samples in the TCGA dataset than in normal breast tissues in the GTEx dataset. RNAscope ISH and immunohistochemistry showed that B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in cancer cells. Expression of B7-H3 and B7-H4 tended to be associated with low-density scores of stromal tumor-infiltrating lymphocytes (TILs) as well as molecular subtypes. Expressions of B7-H3 and B7-H4 were negatively correlated with stromal CD3+ and CD8+ T cell infiltration density. B7-H3 and B7-H4 expression was not associated with survival, which was verified by BreastMark analysis. CONCLUSION: Expression levels of B7-H3 and B7-H4 were independent of clinical outcomes of breast cancer. There was an inverse relationship between the expression of B7-H3 and B7-H4 in breast cancer and the density of stromal TILs and CD8+ T lymphocytes. This inverse relationship may represent a promising target in the field of breast cancer immunotherapy.

11.
Am J Trop Med Hyg ; 102(1): 42-47, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769407

RESUMO

In addition to the complications of leprosy, people affected by leprosy (PALs) can suffer from chronic diseases. We evaluated the recent pattern of deaths among Korean PALs and compared it with that in the general population. We analyzed the death certificate data of 1,359 PALs from 2010 through 2013. The all-cause and cause-specific standardized mortality ratio (SMR) and standardized mortality with 95% CI were calculated. Malignancy had the highest standardized mortality, with 130.9 deaths per 100,000 persons, followed by cardiovascular diseases (CVDs; 85.5 deaths) and respiratory diseases (38.2 deaths). Of malignancies, liver cancer caused the greatest number of cancer deaths (40.0 deaths). The all-cause mortality of PALs was significantly lower than that in the general population, corresponding to an SMR of 0.84 (95% CI 0.79-0.88). Deaths from malignancy and CVDs were significantly lower, corresponding to SMRs (95% CIs) of 0.88 (0.79-0.98) and 0.75 (0.67-0.84), respectively. The death rates for lung and stomach cancers were lower, whereas mortality due to liver cancer was higher, with an SMR of 1.79 (95% CI 1.43-2.22). Except for liver cancer and infection, the causes of mortality of PALs tend to be lower than that in the general population. The most common underlying cause of death in PALs was stroke, followed by ischemic heart disease, liver cancer, and pneumonia.


Assuntos
Hanseníase/epidemiologia , Hanseníase/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Humanos , Hanseníase/complicações , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia
12.
Cancer Epidemiol Biomarkers Prev ; 29(2): 477-486, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31826910

RESUMO

BACKGROUND: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. METHODS: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. RESULTS: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10-8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10-3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10-8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10-8; rs62558833, P = 7.5 × 10-8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. CONCLUSIONS: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. IMPACT: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.

13.
Gastroenterology ; 158(5): 1300-1312.e20, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31884074

RESUMO

BACKGROUND & AIMS: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. METHODS: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10-4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10-5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. CONCLUSIONS: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/epidemiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Feminino , Seguimentos , Humanos , Incidência , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/análise , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais , Reino Unido/epidemiologia
14.
Cancer Res Treat ; 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33421985

RESUMO

Purpose: Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk. Materials and Methods: The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses. Results: Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68-0.90), but not in women (OR, 0.70; 95% CI, 0.47-1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47-0.71 in men and OR, 0.33; 95% CI, 0.18-0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear = 0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11-1.63). Conclusion: Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.

15.
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.


Assuntos
Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu , Predisposição Genética para Doença , Variação Genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Caspase 8 , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , Risco
16.
J Korean Med Sci ; 34(40): e269, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31625294

RESUMO

BACKGROUND: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. METHODS: This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. RESULTS: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97-1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74-0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97-1.20) and 0.80 (95% CI, 0.70-0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52-0.92) for the E2 allele and 1.25 (95% CI, 1.03-1.53) for the E4 allele. CONCLUSION: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.


Assuntos
Apolipoproteínas E/genética , Grupo com Ancestrais do Continente Asiático/genética , Polimorfismo Genético , Idoso , Alelos , Causas de Morte , Estudos de Coortes , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Isoformas de Proteínas/genética , República da Coreia , Fatores de Risco
17.
J Prev Med Public Health ; 52(3): 147-153, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31163949

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the association between body mass index (BMI) and severe lower urinary tract symptoms (LUTS) in Korean males. METHODS: This study was conducted on males aged ≥50 years who participated in the 2011 Korean Community Health Survey. LUTS severity was assessed using the Korean version of the International Prostate Symptom Score (IPSS) questionnaire, and was dichotomized as severe (IPSS >19) and non-severe (IPSS ≤19). BMI was divided into 6 categories: <18.5, 18.5-22.9, 23.0-24.9, 25.0-27.4, 27.5-29.9, and ≥30.0 kg/m2. To evaluate the relationship between BMI and LUTS, a survey-weighted multivariate Poisson regression analysis was performed to estimate prevalence rate ratios (PRRs). Age, smoking status, alcohol intake, physical activity, educational level, household income, and comorbidities were adjusted for in the multivariate model. RESULTS: A U-shaped relationship was detected between BMI and severe LUTS. Compared with a BMI of 23.0-24.9 kg/m2, the PRR for a BMI <18.5 kg/m2 was 1.65 (95% confidence interval [CI], 1.35 to 2.02), that for a BMI of 18.5-22.9 kg/m2 was 1.25 (95% CI, 1.09 to 1.44), that for a BMI of 25.0-27.4 kg/m2 was 1.20 (95% CI, 1.00 to 1.45), that for a BMI of 27.5-29.9 kg/m2 was 1.11 (95% CI, 0.83 to 1.47), and that for a BMI ≥30.0 kg/m2 was 1.85 (95% CI, 1.18 to 2.88). CONCLUSIONS: This study showed that both high and low BMI were associated with severe LUTS.


Assuntos
Índice de Massa Corporal , Sintomas do Trato Urinário Inferior/diagnóstico , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Correlação de Dados , Estudos Transversais , Exercício Físico/psicologia , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Fumar/epidemiologia
18.
Chonnam Med J ; 55(2): 99-103, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161121

RESUMO

Breast cancer is the second most common cancer in Korean women. Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast cancer and are detected in 15-20% of hereditary breast cancer. We investigated the BRCA1 and BRCA2 mutations in 114 familial breast cancer patients using next-generation sequencing. We confirmed 20 different mutations of BRCA1 and BRCA2 in 25 subjects (21.9%). Two such mutations in eight patients were novel (not reported in any variant database or previous study). Six mutations have been reported as disease-causing mutations in public databases. Seven mutations were found only in a single nucleotide polymorphism database and one mutation has been reported in Korea. The BRCA1/2 mutation frequency was similar to that of other studies on familial breast cancer patients in the Korean population. Further studies should examine more cases and mutations of whole exons.

19.
Chonnam Med J ; 55(2): 104-108, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161122

RESUMO

This study evaluated the association between falls and the fear of falling (FOF) with the risk of all-cause mortality in Korean adults. The study enrolled 4,386 subjects aged 50 years and over who participated in the Dong-gu Study. Falls in the past year were categorized as yes or no. Injurious falls were defined as falls that resulted in fractures, head injuries, sprains or strains, bruising or bleeding, or other unspecified injuries. FOF was classified as low or high. The associations of falls and fall-related characteristics with mortality were assessed using Cox proportional hazards models. The average follow-up was 7.8 years. During this period, 255 men and 146 women died. In a fully adjusted model, falls in the past year were not associated with an increased risk of all-cause mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.85-1.58), but a history of injurious falls was associated with an increased risk of mortality (HR 1.36, 95% CI 1.04-1.79). Compared with subjects without a FOF, subjects who were moderately or very afraid of falling had a higher mortality rate (HR 1.26, 95% CI 0.97-1.63). In conclusion, injurious falls and a high FOF increased the risk of all-cause mortality in Koreans. This study suggests that injurious falls and FOF can predict mortality in the general population.

20.
J Psychosoc Oncol ; 37(5): 557-572, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31107193

RESUMO

Purpose: Despite the theoretical and empirical significance of positive aspects of caregiving in caregiver well-being, relatively little is known regarding family-related predictors of caregiver positivity. This study examines whether patient-family communication (p-f communication) mediates the relation between family hardiness and caregiver positivity and whether the mediating effects of p-f communication are moderated by the levels of caregiver depression and anxiety. Design/Sample: This study used secondary data obtained from a large-scale cross-sectional national survey conducted in South Korea. Participants were 544 spousal cancer patient-caregiver dyads recruited from the National Cancer Center and nine government-designated regional cancer centers in South Korea. Methods: To test the hypotheses, a simple mediation model and two moderated mediation tests were conducted using the PROCESS macro for SPSS. Findings: Higher family hardiness was related to higher p-f positive communication and higher caregiver positivity. The effects of family hardiness were partially mediated by p-f communication, controlling for caregiver sex, education, health status, depression and anxiety, time spent caregiving, and patient depression and anxiety, cancer stage, and time since diagnosis. The mediating effects of p-f communication were not significantly moderated by caregiver depression and anxiety. Conclusions/Implications: Health care professionals could consider p-f communication as a reasonable target of intervention to increase caregiver positivity, even for caregivers with heightened depression and anxiety.


Assuntos
Cuidadores/psicologia , Comunicação , Relações Familiares/psicologia , Resiliência Psicológica , Idoso , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , República da Coreia/epidemiologia
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