Search PubMed⌕ Search

Biomedical subjects

Daehee Kang

Publications and source records attributed to Daehee Kang.

63 records · Page 4Linked to original sources

Influence of polymorphism of GSTM1 gene on association between glycophorin a mutant frequency and urinary PAH metabolites in incineration workers.

The association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as an internal measure of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator, was determined to establish whether genetic polymorphisms of glutathione S-transferase (GST) isoforms GSTM1 and GSTT1 play a role. Eighty-one workers including 38 employees directly involved in incinerating industry wastes were recruited from a company located in South Korea. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometric assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex polymerase chain reaction (PCR) method. Urinary 1-OHPG levels were higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs. An increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels. When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 genotype. These results suggest that the association between urinary 1-OHPG and GPA mutation might be modulated by the GSTM1 genotype.

Adult↗

Combined COMT and GST genotypes and hormone replacement therapy associated breast cancer risk.

Our previous studies suggested that both COMT and GST genotypes might modify individual breast cancer risk. Here, we extended the studies to examine the potential combined effect of these genotypes in susceptibility to breast cancer. Our study population consisted of 483 Finnish breast cancer cases and 482 population control subjects. The odds ratios (ORs) and (95%) confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected confounding factors. No significant increase in the overall breast cancer risk was seen for any combinations of the studied genotypes. However, a substantially increased risk of breast cancer was seen for women who had used hormone replacement therapy (HRT) and simultaneously carried the COMT-L allele containing genotypes and either the GSTP1 Ile/Ile genotype (OR 4.10, 95% CI 1.24-13.6) or the GSTT1 null genotype (OR 4.19, 95% CI 1.30-13.5). These associations appeared to be mainly attributable to long-term users of HRT; the respective ORs were 7.00 (95% CI 1.21-40.6) and 8.36 (95% CI 1.44-49.0) among the users of HRT of more than 30 months. In addition, the combination of COMT-L allele containing genotypes with the GSTM1 null genotype posed a remarkably increased risk (OR 9.10, 95% CI 1.84-45.0) of breast cancer in this study group. These results suggest that the use of HRT could substantially increase the risk of breast cancer among women with specific combinations of the at-risk genotypes of COMT and GST genes.

Adult↗

Epidemiology of breast cancer in Korea: occurrence, high-risk groups, and prevention.

Breast cancer ranks second or third to uterine cervix cancer and stomach cancer as a cause of death in women, and as a common site of primary cancer. The large difference in its incidence between Westernized and non-Westernized countries is remarkable. There is a linear increase with age that is observed in Western countries, which are high-incidence areas, on the contrary to the inverted V shape curve seen in Asian countries. Epidemiologic studies conducted in Korea have shown that an older age, a family history of breast cancer, early menarche, late menopause, late full-term pregnancy, and never having had a breast-fed child are primary risk factors in the development of breast cancer. The estrogen-augmented-by-progesterone hypothesis explains the roles of these factors to some extent. On the other hand, recent molecular studies have revealed the existence of novel gene environmental interactions. Epidemiological features suggest that the breast cancer incidence rate in Korea will increase, but the age specific curve would not be changed in keeping with what is observed in Western countries. Strategies aimed at controlling breast cancer that include the screening guidelines and the identification of individual predispositions may give us further insights into both the etiology and the prevention of breast cancer.

Breast Neoplasms↗

Korean Multi-center Cancer Cohort Study including a Biological Materials Bank (KMCC-I).

Cohort studies of human populations have provided the most convincing evidence of links between exposure to specific agents and cancer. The Korean Multi-center Cancer Cohort (KMCC-II) is a multi-center prospective cohort designed to investigate the relationship between exposures to environmental factors, lifestyle factors, host factors and the risk of cancer in Korea. Data on general lifestyle, physical activity, diet, reproductive factors, and agricultural exposures have been collected by direct interview since 1993. Anthropometric measurements and some clinical laboratory findings have also been recorded. This cohort is characterized by the exclusion of cancer cases at the time of recruitment through cancer screening by physicians. The number of cancer-free subjects in the cohort at present totals some 35,692 men and women aged over 35 (121,856 person-years as of December 2000). Of the KMCC-II, 11,045 subjects who have donated their blood and/or urine sample were classified as the KMCC-I. In order to provide an opportunity to incorporate various biomarkers of exposure and the effect of exposure, as well as information on genetic susceptibility, a biological materials bank with blood (plasma, or serum buffy coat, packed erythrocytes) at -70oC and urine supernatants at -20oC has been established for future studies on cancer etiology. The total number of the KMCC-I is 10,694 for the blood bank and 8,907 for the urine bank (total number of observation in person-year = 47,002). Follow-up for cancer incidence has commenced based on an active surveillance system conducted mainly through telephone interview by health personnel or through diagnosis by physicians in each district, and a passive surveillance system through record linkages between the national cancer registry, the national death certificate system, and health insurance medical records databases in Korea. Moreover, this cohort study is expected to play a significant role in assessing the role of genes in the etiology of cancer. These include the determination of the cost-efficiency and reliability of the nested case-control approach, using the cohort, for exploring gene-disease associations and gene-environmental interactions using reduced sample sizes. Along with other cancer cohorts, the KMCC study could eventually provide convincing evidence on new etiologies of cancer in the Asian-Pacific region.

Journal Article↗

Asthma attack associated with oxidative stress by exposure to ETS and PAH.

UNLABELLED: Asthma is primarily an airways inflammatory disease, and the bronchial airways have been shown to be particularly susceptible to oxidant-induced tissue damage. OBJECTIVE: The purpose of this study was to investigate whether pulmonary inflammation in asthma is associated with exposure to environmental oxidants such as polycyclic aromatic hydrocarbon (PAH) and environmental tobacco smoke (ETS). METHOD: We assessed the exposure level of PAH and ETS by using urinary 1-hydroxypyrene glucuronide (1-OHPG) and cotinine. We estimated oxidative damage and inflammatory cytokine levels from 16 asthma patients and 16 patients in stable conditions 1 to 2 months later. RESULTS: Our study showed that the levels of oxidative damage, as measured by malondialdehyde (MDA), were significantly increased (p = 0.006) during the asthma attacks. Proinflammatory and anti-inflammatory cytokines were both increased during the asthma attacks compared to the stable conditions at follow-up. Interleukin (IL-6) and IL-10 were especially increased significantly (p = 0.015 and p < 0.001, respectively). Correlations were observed between inflammatory cytokines such as IL-6 and IL-1beta (p = 0.034). CONCLUSION: This study supports the results of in vitro studies that oxidative stress, specifically lipid peroxidation, contributes to the pathophysiology of asthma. Therefore, environmental interventions based on this better understanding are needed to significantly reduce oxidant stress and prevent or minimize the development of asthmatic symptoms.

Adolescent↗

Full sequencing analysis of estrogen receptor-alpha gene polymorphism and its association with breast cancer risk.

BACKGROUND: The estrogen receptor plays a critical role in breast cancer development and progression. So the genetic polymorphism of ER-alpha gene could affect cancer risk and phenotype. MATERIALS AND METHODS: We fully sequenced the ER-alpha gene to investigate its single nucleotide polymorphisms (SNPs) in 100 breast cancer patients and 100 controls. RESULTS: Six novel polymorphism in the control and 11 in cancer patients were found. The G/G genotype at C975 G and A/A genotype at G1782 A had a protective effect against breast cancer when compared to other genotypes (OR = 0.3 and 0.3, respectively). 975G allele was associated inversely with the p53 expression and positively with the bcl-2 expression in cancer with borderline significance. Combining this result with our previous study, these associations became more significant (p = 0.005 and 0.019, respectively). CONCLUSION: Polymorphisms in ER-alpha gene can affect the breast cancer susceptibility and may be related to other protein expression, such as p53 and bcl-2.

Amino Acid Sequence↗

Genomic epidemiology cohorts in Korea: present and the future.

Human genome epidemiology involves the application of genetic technology to assess the impact of variations at the DNA level on health and disease. Recent developments in molecular biology allow epidemiologists to use biomarkers to determine an individuals predisposition to disease and to detect disease at an early stage. Moreover, advances in genomics and proteomics could play a central role in research into disease prediction and prevention. Large scale population-based cohort prospective studies offer the most comprehensive approach to the delineation of gene function, the effects of the environment, and their interactions. The Korean Multi-center Cancer Cohort (KMCC), under construction since 1993, is the first multi-center prospective cohort to identify risk factors for cancer in Korea. Data on general lifestyle, physical activity, diet, reproductive factors, and agricultural exposure are obtained through direct interview using a structured questionnaire. Anthropometric measurements and clinical laboratory findings are also collected using a web-based data entry system. Moreover, biological materials have been banked [blood (serum, plasma, buffy coat, packed erythrocytes) is stored at -70 degrees C and urine at -20 degrees C] for future analysis. Several other cohorts including the Korean National Cancer Center (KNCC) Cohort, the Korean Health Examinees (KOEX) Cohort, the Korean Health and Genome Epidemiologic Study (KHGES), and the Yang Pyeong Cohort have also been launched since the KMCC cohort was initiated. Even though these cohorts have collected similar data and biospecimen, questionnaires and protocols used have not been standardized. However, these cohort studies are of increased scope and have been designed to detect risk factors for cardiovascular disease, metabolic syndrome, and cancer. Subjects have been followed up actively by health personnel in different regions and by using record linkages with the central cancer registry, and the national death certificate and national health insurance claim databases. As of August 2004, the total number of subjects enrolled in all cohorts with archived biologic specimens was around 80,000. A new genomic cohort has been launched since 2001 in Korea, for which the target number of subjects is 250,000 men and women over the next 5 years. This article describes the goals and the designs of each of the above-mentioned cohorts.

Anthropometry↗

Gene amplification using DNA from human spot urine samples.

The purpose of this study was to test the amplification of DNA from human urinary sediment for molecular epidemiological studies. Twenty-six urine samples were obtained from healthy volunteers. Polymerase chain reactions (PCR) for methylenetetrahydrofolate reductase (MTHFR), beta-globin, and N-acetyltransferase 2 (NAT2) was conducted using genomic DNA isolated from the urine. The MTHFR and beta-globin genes were amplified successfully from all the urine DNA samples while the NAT2 gene was amplified in 88.5% of cases. The median yield of DNA was 0.28 microg from the 10 ml urine samples, sufficient amounts of DNA being contained in urinary sediments for amplification of all three genes. This result indicates that urine can be used as a DNA source for PCR-based molecular epidemiological studies.

Adolescent↗