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BACKGROUND: Single-parent families with children with disabilities need greater attention given the notable increase in their number and their additional difficulties. Single parents in East Asian countries, especially, may face greater risks than their peers elsewhere, given the region's unique cultural background. METHOD: The study used a mixed methods design; we administered a risk assessment survey to 354 families of children with intellectual and developmental disabilities and conducted in-depth interviews with eight single parents. RESULTS: Compared to two-parent families, single-parent families faced greater risks with respect to family relationships, economic status and legal rights. In the interviews, single parents reported a range of challenges, including sole parental responsibilities, poor physical and mental health, social isolation and alienation, the stress of juggling care and work, and difficulty accessing services. CONCLUSION: These findings offer implications for future policy and practices concerning single parents in South Korea.
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Deficiência Intelectual , Pais Solteiros , Criança , Humanos , Deficiências do Desenvolvimento , Pais/psicologia , Fatores SocioeconômicosRESUMO
BACKGROUND: Self-directed supports (SDS) are a model of disability service delivery that focuses on supporting increased decision-making authority and budget autonomy for people with disabilities and their families. This study identifies supervisory and administrative staff's perspectives within a self-directed, individualised budgeting programme for people with intellectual and developmental disabilities. METHOD: Data were collected through 28 face-to-face interviews with supervisory and fiscal administrative staff in Minnesota, USA. RESULTS: A qualitative analysis of these interviews resulted in four major themes: (1) the benefits of SDS, (2) the relationship between SDS and person-centred strategies, (3) the perception that a natural tension arises when balancing person-centred approaches with the need for consistent and fair state policy-including rules and regulations within state systems and (4) the unique challenges related to SDS benefits and challenges occurring across Minnesota. CONCLUSIONS: The results indicate the importance of providing effective communication and training to all stakeholders.
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Pessoas com Deficiência , Deficiência Intelectual , Criança , Deficiências do Desenvolvimento , Humanos , MinnesotaRESUMO
BACKGROUND: Future planning has emerged as a global issue for families of individuals with intellectual and developmental disabilities due to the longer lives and limited long-term services and supports in the adult disability system. While it has received greater attention, most future planning studies only included parents of individuals with intellectual and developmental disabilities within the context of European or American countries. The purpose of this study was to examine future planning among siblings of individuals with intellectual and developmental disabilities in South Korea. METHOD: In this study, 185 Korean siblings of individuals with intellectual and developmental disabilities responded to a survey. RESULTS: Few siblings engaged in future planning activities and reported a range of barriers to conduct future planning. Further, greater future planning involvement was associated with older siblings, greater advocacy level and greater sibling caregiving. CONCLUSION: For future research, culturally relevant measures and intervention should be addressed.
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Deficiência Intelectual , Irmãos , Adulto , Cuidadores , Criança , Deficiências do Desenvolvimento , Humanos , República da CoreiaRESUMO
BACKGROUND: It is evident that people with disabilities worldwide face digital divide; although this divide has been mitigated owing to greater access to technologies, a gap remains in terms of Internet use. Given that South Korea has one of the highest Internet access rates, it is necessary to examine how adults with intellectual and developmental disabilities (IDD) access the Internet, and what correlates with Internet usage. METHOD: A total of 298 adults with IDD in South Korea participated in the survey. RESULTS: The participants reported benefits from the Internet including increased opportunities for leisure and entertainment, updated news and networking with friends. Internet access was found to be pervasive among people of younger ages and less severe disabilities. Further, Internet usage corresponded to material access, digital literacy and a positive attitude towards digital applications. CONCLUSIONS: Targeted digital literacy programmes can be developed for adults with IDD.
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Pessoas com Deficiência , Deficiência Intelectual , Adulto , Criança , Deficiências do Desenvolvimento/epidemiologia , Humanos , Internet , Uso da Internet , República da CoreiaRESUMO
BACKGROUND AND AIM: In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. METHODS: We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5%), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. RESULTS: Over a median 3.5 years of follow-up (range = 0.1-4.4), overt HE developed in 28 patients (18.2%). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher Model for End-Stage Liver Disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. CONCLUSIONS: In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus, additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.
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Estudos de Associação Genética , Glutaminase/genética , Encefalopatia Hepática/genética , Rim/enzimologia , Repetições de Microssatélites/genética , Regiões Promotoras Genéticas/genética , Sequências de Repetição em Tandem/genética , Idoso , Alelos , Povo Asiático , Ásia Oriental/epidemiologia , Feminino , Seguimentos , Encefalopatia Hepática/epidemiologia , Humanos , Incidência , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The present study compared meaning-making coping among cancer patients in Sweden and South Korea, with a focus on the sociocultural context. Semi-structured interviews were conducted with 51 Swedes and 33 Koreans. The results showed significant differences between the two countries as well as similarities in existential, spiritual, and religious coping. For example, Swedes primarily used meaning-making coping as a means of meditation or relaxation, whereas Koreans relied on coping with prayer and using healthy foods as a means to survive. The present study confirms the significance of investigating cultural context when we explore the use of meaning-making coping among people who have experienced cancer.
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Adaptação Psicológica , Comparação Transcultural , Neoplasias/psicologia , Religião e Medicina , Espiritualidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , República da Coreia , SuéciaRESUMO
OBJECTIVE: The aim of the study was to develop a reliable and easy-to-use risk-scoring system (RSS) to predict lymph-node metastasis (LNM) and determine the feasibility of endoscopic submucosal dissection for mucosa-confined signet ring cell carcinomas (SRCs). BACKGROUND: Fewer LNM and better survival rates have been reported for early gastric SRCs compared with other undifferentiated early gastric cancers (EGCs). METHODS: Data from 1544 patients with mucosa-confined SRCs were reviewed. Stepwise logistic regression analysis determined the independent predictors of LNM. Risk scores were based on the final predictive factors for LNM, and performance was internally validated using a split-sample approach. External validation was also performed in an independent dataset (n = 208) to assess the discriminatory power of the RSS. RESULTS: The overall LNM incidence was 3.8% (57/1544). Three risk factors (tumor size ≥1.7âcm, tumors of elevated type, and lymphatic-vascular involvement) were significantly associated with LNM. These factors were incorporated into the RSS, and were assigned scores ranging from 0 to 4. The area under the receiver-operating characteristic curve for predicting LNM after internal and external validation was 0.68 (95% confidence interval, 0.0793-0.2865) and 0.686 (95% confidence interval, 0.618-0.748), respectively. A score of 2 points was the optimal cut-off value for LNM prediction, and the overall diagnostic accuracy was 96%. LNM were found in 2.9% and 23.8% of the low and high-risk groups of the RSS, respectively. CONCLUSIONS: A RSS may help to predict LNM and evaluate endoscopic submucosal dissection feasibility in patients with intramucosal SRC.
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Carcinoma de Células em Anel de Sinete/cirurgia , Metástase Linfática/patologia , Medição de Risco/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/patologia , Feminino , Gastrectomia , Mucosa Gástrica/patologia , Gastroscopia , Humanos , Incidência , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
OBJECTIVES: Few studies have compared the long-term outcomes of endoscopic resection and surgery. The aim of this study was to compare the long-term outcomes of endoscopic resection with those of surgery for early gastric cancer (EGC). METHODS: We reviewed prospectively collected data of patients who had undergone endoscopic resection (1,290 patients) or surgery (1,273 patients) for EGC. To reduce the effect of selection bias, we performed a propensity score-matching analysis between the two groups. The primary outcome was overall survival (OS). The secondary outcomes were disease-specific survival, disease-free survival (DFS), recurrence-free survival (RFS), occurrence of metachronous gastric cancer, treatment-related complications, length of hospital stay, and 30-day outcomes. The study was designed as a non-inferiority study and tested in an intention-to-treat analysis. RESULTS: In a propensity-matched analysis of 611 pairs, the 10-year OS proportion was 96.7% in the endoscopic resection group and 94.9% in the surgery group (P=0.120) (risk difference -1.8%, 95% confidence interval (CI) -4.04-0.44, Pnon-inferiority=0.014), which met the non-inferiority criterion. In contrast, the 10-year RFS proportion was 93.5% in the endoscopic resection group and 98.2% in the surgery group (P<0.001) (risk difference 4.7%, 95% CI 2.50-6.97, Pnon-inferiority=0.820), which did not meet the non-inferiority criterion, mainly because of metachronous recurrence in the endoscopic resection group. The rate of early complications was higher in the endoscopic resection group than in the surgery group (9.0 vs. 6.6%, P=0.024), whereas the rate of late complications was higher in the surgery group than in the endoscopic resection group (0.5 vs. 2.9%, P<0.001). In the multiple Cox regression analysis, patient's age, the comorbidity index, the performance index, sex, tumor morphology, and depth of invasion were predictors of OS in patients with EGC. CONCLUSIONS: Endoscopic resection might not be inferior to surgery with respect to OS in patients with EGC lesions that meet the absolute or expanded criteria. However, DFS, RFS, and metachronous RFS might be lower after endoscopic resection than after surgery.
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Gastrectomia/métodos , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Endoscopia do Sistema Digestório , Feminino , Mucosa Gástrica/patologia , Humanos , Tempo de Internação , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
The present study aimed to explore the use of meaning-making coping (existential, spiritual, and religious coping) among cancer patients in Korea and to investigate the impact of culture on their choice of coping methods. Thirty-three participants with various kinds of cancer were interviewed. Four different kinds of coping resources emerged from analyses of the interview transcripts: (1) belief in the healing power of nature; (2) mind-body connection; (3) relying on transcendent power; and (4) finding oneself in relationships with others. The findings of this study suggest the importance of investigating cultural context when exploring the use of the meaning-making coping strategies in different countries.
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Adaptação Psicológica , Atitude Frente a Saúde , Existencialismo/psicologia , Neoplasias/psicologia , Adulto , Feminino , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Triple-negative breast cancer (TNBC) is associated with a poor prognosis and metastatic growth. TNBC cells frequently undergo macroautophagy/autophagy, contributing to tumor progression and chemotherapeutic resistance. ANXA2 (annexin A2), a potential therapeutic target for TNBC, has been reported to stimulate autophagy. In this study, we investigated the role of ANXA2 in autophagic processes in TNBC cells. TNBC patients exhibited high levels of ANXA2, which correlated with poor outcomes. ANXA2 increased LC3B-II levels following bafilomycin A1 treatment and enhanced autophagic flux in TNBC cells. Notably, ANXA2 upregulated the phosphorylation of HSF1 (heat shock transcription factor 1), resulting in the transcriptional activation of ATG7 (autophagy related 7). The mechanistic target of rapamycin kinase complex 2 (MTORC2) played an important role in ANXA2-mediated ATG7 transcription by HSF1. MTORC2 did not affect the mRNA level of ANXA2, but it was involved in the protein stability of ANXA2. HSPA (heat shock protein family A (Hsp70)) was a potential interacting protein with ANXA2, which may protect ANXA2 from lysosomal proteolysis. ANXA2 knockdown significantly increased sensitivity to doxorubicin, the first-line chemotherapeutic regimen for TNBC treatment, suggesting that the inhibition of autophagy by ANXA2 knockdown may overcome doxorubicin resistance. In a TNBC xenograft mouse model, we demonstrated that ANXA2 knockdown combined with doxorubicin administration significantly inhibited tumor growth compared to doxorubicin treatment alone, offering a promising avenue to enhance the effectiveness of chemotherapy. In summary, our study elucidated the molecular mechanism by which ANXA2 modulates autophagy, suggesting a potential therapeutic approach for TNBC treatment.Abbreviation: ATG: autophagy related; ChIP: chromatin-immunoprecipitation; HBSS: Hanks' balanced salt solution; HSF1: heat shock transcription factor 1; MTOR: mechanistic target of rapamycin kinase; TNBC: triple-negative breast cancer; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3.
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Anexina A2 , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Autofagia/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Fatores de Transcrição de Choque Térmico/genética , Anexina A2/genética , Linhagem Celular Tumoral , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Doxorrubicina , SirolimoRESUMO
BACKGROUND: The COVID-19 pandemic has reinforced social inequality in marginalized groups. People with disabilities (PWD) are particularly restricted in their activities and lives due to the pandemic and experiencing more difficulties than the general population. OBJECTIVE: This study aims to explore the extent of the digital divide between PWD and people without disabilities (PWOD) during the COVID-19 pandemic in South Korea. METHODS: This study relied on the cross-sectional secondary data from the 2020 Digital Divide Survey conducted in Korea. We performed a series of bivariate analyses on the data of 5575 PWOD and 1781 PWD (18-69 years old) to compare Internet usage and various types of digital services related to the pandemic. RESULTS: We identified significant differences between PWOD and PWD in their Internet usage change during the pandemic. A higher number of PWD reported that their Internet usage with both computers and mobile devices remained similar to the pre-pandemic period while that of PWOD reported that their Internet usage via the same has increased. Significant gaps were found in the usage change of the five digital services with the largest gap in that of social networking services between PWOD and PWD. Further, PWOD were likelier to be aware of, utilize, and perceive the usefulness of digital services during the COVID-19 pandemic including application, information, delivery, and subscription services. CONCLUSION: To ensure better post-pandemic outcomes for marginalized groups including PWD, the governments and authority agencies must facilitate digital access and services with appropriate accommodations needed by those populations.
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COVID-19 , Exclusão Digital , Pessoas com Deficiência , Adolescente , Adulto , Idoso , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: Societal inequalities caused by the digital divide between people with disabilities and people without disabilities are a social justice issue. Internet use to acquire beneficial outcomes has increasingly been the focus of the digital divide. OBJECTIVE: This study investigates the extent to which outcomes of Internet use differ between individuals with (PWD) and without disabilities (PWOD) and determinants of outcomes of Internet use. METHODS: We conducted a series of multiple linear regression analyses using cross-sectional data of 1762 PWD and 5491 PWOD from the Digital Divide Survey conducted in Korea in 2018. RESULTS: We determined gaps in Internet access, skill, motivation, and outcomes between PWD and PWOD. PWOD reported significantly higher Internet access, skill, and motivation, and they also acquired more beneficial outcomes on all outcome domains than PWD. Further, PWOD with higher education degrees, higher household incomes, higher motivation towards Internet use, and greater digital skills acquired more beneficial outcomes of Internet use. Moreover, disability status, motivation to use the Internet, and digital skills were the most salient determinants of outcomes of Internet use, both collectively and specifically out of the five domains. CONCLUSION: The government should move forward to closing the gap in outcomes of Internet use between PWD and PWOD by providing programs and interventions to promote Internet use and enhance digital skills as well as by increasing web accessibility and incentives system.
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Pessoas com Deficiência , Uso da Internet , Estudos Transversais , Humanos , República da Coreia , Inquéritos e QuestionáriosRESUMO
Previous studies have shown that participation in social networking sites (SNSs) enhances users' knowledge, social capital, and quality of life. However, people with intellectual developmental disabilities (PIDD) do not use SNSs to the same extent as the general population does. This study aimed to explore the experiences of those PIDD in South Korea who use social media. Data were collected through face-to-face interviews with 20 PIDD. The study participants reported benefits associated with the use of SNSs, which included enhanced social capital, self-confidence, and positive self-image. Participants also used SNSs to maintain friendships, initiate new relationships, and engage in self and community advocacy. Safety concerns were also reported by the participants. The study concluded that SNSs can be used as tools for promoting community inclusion and developing social capital for PIDD. However, the outcomes of using SNSs depend on the availability of support provided by one's network. The absence of support may result in frustration and even exploitation. With effective support, SNSs become powerful tools that can be used by PIDD to combat social isolation through creating ample opportunities for social inclusion.
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OBJECTIVE: The superficial spreading type of early gastric cancer (EGC) possesses unique features different from other types of EGC. We aimed to elucidate the clinicopathological features of superficial spreading type of EGC. MATERIAL AND METHODS: We analyzed 1455 EGC lesions from 1398 patients who had undergone surgical treatment at Samsung Medical Center from 2000 to 2002. Then the clinicopathological features of 224 superficial-spreading EGC lesions (15.4%) was compared to that of 1231 lesions of a common type of EGC. RESULTS: In the superficial spreading type of EGC, the incidence of undifferentiated type and submucosal invasion were higher than those of common type of EGC (55.4 vs 38.0%, p < .01 and 58.5 vs 37.8%, p < .01, respectively). Lymph node metastasis and lymphovascular invasion were more frequent in superficial spreading type than in common type of EGC (19.2 vs 7.6%, p < .01 and 15.2 vs 7.4%, p < .01, respectively). There was no difference in recurrence rate or 5-year survival rate between the two groups. CONCLUSION: Considering higher risk of submucosal invasion and lymph node metastasis in superficial spreading type, a careful consideration should be done before the application of endoscopic resection to the superficial spreading type of EGC.
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Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Increased consumption of fructose may play an important role in the epidemic of metabolic syndrome and may presage the development of diabetes, cardiovascular disease, and chronic kidney disease. Once in the cell, fructose is phosphorylated by ketohexokinase (KHK), leading to consumption of ATP, formation of AMP, and generation of uric acid through xanthine oxidoreductase (XOR). This study aimed to examine the direct effects of fructose in human kidney proximal tubular cells (HK-2) and whether they are mediated by the fructose metabolism via KHK. At a similar concentration to that observed in peripheral blood after a meal, fructose induced production of monocyte chemotactic protein 1 (MCP-1) and reactive oxygen species in HK-2 cells. Knockdown of KHK by stable transfection with small hairpin RNA demonstrated that these processes were KHK dependent. Several antioxidants, including specific inhibitors of NADPH oxidase and XOR, prevented MCP-1 secretion. We detected XOR mRNA in HK-2 cells and confirmed its activity by identifying uric acid by mass spectrometry. Fructose increased intracellular uric acid, and uric acid induced production of MCP-1 as well. In summary, postprandial concentrations of fructose stimulate redox- and urate-dependent inflammatory mediators in proximal tubular cells.
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Frutoquinases/metabolismo , Frutose/metabolismo , Mediadores da Inflamação/metabolismo , Túbulos Renais Proximais/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Quimiocina CCL2/biossíntese , Primers do DNA/genética , Frutoquinases/antagonistas & inibidores , Frutoquinases/genética , Frutose/farmacologia , Humanos , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Transfecção , Ácido Úrico/farmacologia , Xantina Desidrogenase/genética , Xantina Desidrogenase/metabolismoRESUMO
Uric acid (UA) can be directly converted to allantoin enzymatically by uricase in most mammals except humans or by reaction with superoxide. UA can react directly with nitric oxide to generate 6-aminouracil and with peroxynitrite to yield triuret; both of these metabolites have been identified in biological samples. We now report a validated high-performance liquid chromatography and tandem mass spectrometry method for the determination of these urinary UA metabolites. Urine samples were diluted 10-fold, filtered and directly injected onto HPLC for LC-MS/MS analysis. The urinary metabolites of UA were separated using gradient HPLC. Identification and quantification of UA urinary metabolites was performed with electrospray in positive ion mode by selected-reaction monitoring (SRM). Correlation coefficients were 0.991-0.999 from the calibration curve. The intra- and inter-day precision (R.S.D., %) of the metabolites ranged from 0.5% to 13.4% and 2.5-12.2%, respectively. In normal individuals (n=21), urinary allantoin, 6-aminouracil and triuret, were 15.30 (+/-8.96), 0.22 (+/-0.12), and 0.12 (+/-0.10) microg/mg of urinary creatinine (mean (+/-S.D.)), respectively. The new method was used to show that smoking, which can induce oxidative stress, is associated with elevated triuret levels in urine. Thus, the method may be helpful in identifying pathways of oxidative stress in biological samples.
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Alantoína/urina , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Uracila/análogos & derivados , Ureia/análogos & derivados , Calibragem , Humanos , Padrões de Referência , Reprodutibilidade dos Testes , Uracila/urina , Ureia/urinaRESUMO
This study analyzed life after injury for burn survivors using the photovoice research method. Study participants were six burn survivors who lived in the community after being discharged from the hospital. These six participants engaged in a series of photovoice workshops and activities that took place over a period of 4 months. The study results were as follows: burn survivors were able to achieve a positive body image during their physical recovery. They overcame many psychological difficulties that accompanied their burn injuries. Their attitudes toward their lives changed positively. The greatest influence in bringing out these changes was support from family, friends, and other burn survivors. They were better able to fight against social oppression with their recovered self-esteem. The participants had experienced a disconnect from the activities and interpersonal relationships they had prior to their injury owing to long-term hospital stays and time away from work. However, as they began new social activities, they were able to establish new interpersonal relationships. Based on the research results, this study suggests that medical, psychological, and social approaches as well as positive changes in social attitude are necessary to support burn survivors' recovery.
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Queimaduras/psicologia , Acontecimentos que Mudam a Vida , Fotografação , Sobreviventes/psicologia , Atitude , Imagem Corporal , Pessoas com Deficiência , Emprego , Humanos , Relações Interpessoais , República da Coreia , Apoio SocialRESUMO
Caspase-3 (CASP-3) is a primary effector CASP that executes programmed cell death, and it plays an important role in the development and progression of cancer. Polymorphisms in the CASP-3 gene may influence CASP-3 production and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we first screened for polymorphisms in the CASP-3 gene by direct sequencing of genomic DNA samples from 27 healthy Koreans, and then evaluated their associations with lung cancer in a case-control study that consisted of 582 lung cancer patients and 582 healthy controls. Individuals with at least one variant allele of the -928A > G, 77G > A, and 17532A > C polymorphisms were at a significantly decreased risk for lung cancer in comparison to the carriers with each homozygous wild-type allele [adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.62-1.00, P = 0.05; adjusted OR = 0.78, 95% CI = 0.61-0.99, P = 0.04; and adjusted OR = 0.74, 95% CI = 0.58-0.95, P = 0.02, respectively]. Consistent with the results of genotyping analysis, the GAGC haplotype carrying the variant allele at all of the -928A > G, 77G > A, and 17532A > C loci was associated with a significantly decreased risk of lung cancer compared to the AGGA haplotype carrying no variant alleles at the three loci (adjusted OR = 0.66, 95% CI = 0.51-0.86, P = 0.002 and Bonferroni corrected P = 0.008). These results suggest that the CASP-3 polymorphisms and their haplotypes contribute to the genetic susceptibility to lung cancer.
Assuntos
Caspase 3/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma/secundário , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/secundário , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Caspase 3/metabolismo , Feminino , Haplótipos/genética , Humanos , Coreia (Geográfico)/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , FumarRESUMO
BACKGROUND: Survivin is an apoptosis inhibitor and plays an important role in the development and progression of cancer. Polymorphisms in the survivin gene may influence survivin production or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between survivin polymorphisms and the risk of lung cancer in a Korean population. METHODS: We first screened for polymorphisms in the survivin gene by direct sequencing of genomic DNA samples from 27 healthy Koreans. We selected identified SNPs based on their frequency, linkage disequilibrium status and haplotype tagging status, and then genotyped the selected SNPs in 582 lung cancer patients and 582 healthy controls who were frequency matched for age and gender. RESULTS: We identified 8 single nucleotide polymorphisms (SNPs): 6 known SNPs [-644T>C, -625G>C, -31C>G, 9194A>G (K129E), 9386T>C and 9809T>C] and 2 novel SNPs (9974C>T and 10347G>A). Among the SNPs studied, only the -31C>G genotype distribution was significantly different between the cases and controls (P=0.04). Individuals with at least one -31G allele were at a significantly decreased risk of lung cancer compared to those individuals with the -31CC genotype [adjusted odds ratio (OR)=0.74, 95% confidence interval (CI)=0.57-0.96, P=0.02]. When the lung cancer cases were categorized by tumor histology, the -31G allele was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.59, 95% CI=0.41-0.84, P=0.003). Consistent with the results of the genotyping analysis, the -625G/-31G/9194A/9809T haplotype carrying the -31G allele was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.56, 95% CI=0.40-0.77, P=0.0004). The promoter assay revealed the -31G allele to have a significantly lower promoter activity than the -31C allele. CONCLUSION: These results suggest that the survivin -31C>G polymorphism influences survivin expression, thus contributing to the genetic susceptibility to lung cancer.