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5 "Genetic Polymorphism"
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Original Articles
Placental Superoxide Dismutase, Genetic Polymorphism, and Neonatal Birth Weight.
Yun Chul Hong, Kwan Hee Lee, Moon Whan Im, Young Ju Kim, Eun Hee Ha
J Prev Med Public Health. 2004;37(4):306-311.   Published online November 30, 2004
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AbstractAbstract PDF
BACKGROUND
The roles of antioxidants in the placenta and genetic susceptibility to oxidant chemicals in relation to neonatal birth weight have not been elucidated. We determined whether the level of placental manganese superoxide dismutase (MnSOD) and its genetic polymorphism plays any role in oxidative stress and neonatal birth weight. METHODS: We measured placental MnSOD and determined MnSOD genetic polymorphism among 108 pregnant women who were hospitalized for delivery and their singleton live births in Korea. Main outcome measurements are maternal urinary malondialdehyde (MDA) and birth weight. RESULTS: Maternal urinary concentrations of MDA were significantly associated with neonatal birth weight (P=0.04). The enzyme level of placental MnSOD was also significantly associated with MDA concentration (P=0.04) and neonatal birth weight (P< 0.01). We observed dose-response relationships between placental MnSOD and maternal urinary MDA, and neonatal birth weight after adjusting for maternal weight, height, age, and neonatal sex. After controlling for covariates, MnSOD variant genotype increased maternal urinary MDA concentrations (P< 0.01) and reduced birth weight by 149 gm (P=0.08). CONCLUSIONS: This study demonstrates that the placental level of MnSOD during pregnancy significantly affects fetal growth by reducing oxidative stress, and that genetic polymorphism of MnSOD probably modulate the effects of oxidants on fetal growth.
Summary
The Exposure Status and Biomarkers of Bisphenol A in Shipyard Workers.
Sang Baek Koh, Cheong Sik Kim, Jun Ho Park, Bong Suk Cha, Jong Ku Park, Heon Kim, Soung Hoon Chang
Korean J Prev Med. 2003;36(2):93-100.
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OBJECTIVES
Because shipyard workers are involved with various manufacturing process, they are exposed to many kinds of hazardous materials. Welders especially, are exposed to bisphenol-A (BPA) during the welding and flame cutting of coated steel. This study was conducted to assess the exposure status of the endocrine disruptor based on the job-exposure matrix. The effects of the genetic polymorphism of xenobiotic enzyme metabolisms involved in the metabolism of BPA on the levels of urinary metabolite were investigated. METHODS: The study population was recruited from a shipyard company in the K province. A total of 84 shipbuilding workers 47 and 37 in the exposed and control groups, respectively, were recruited for this study. The questionnaire variables included, age, sex, use of personal protective equipment, smoking, drinking and work duration. The urinary metabolite was collected in the afternoon and correction made for the urinary creatinine concentration. The of the CYP1A1, CYP2E1 and UGT1A6 genotypes were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods with the DNA extracted from venous blood. RESULTS: The urinary BPA level in the welders group was significantly higher than in the control group (p< 0.05). The urinary BPA concentration with the wild type UGT1A6 was higher than the other UGT1A6 genotypes, but with no statistical significant. From themultiple regression analysis of the urinary BPA, the regression coefficient for job grade was statistically significant (p< 0.05). CONCLUSIONS: The grade of exposure to BPA affected the urinary BPA concentration was statistically significant. However, the genetic polymorphisms of xenobiotics enzyme metabolism were not statistically significant. Further investigation of the genetic polymorphisms with a larger sample size is needed.
Summary
PCR and RFLP-based CYP2D6(B) and CYP2D6(T) Genotyping for Korean Lung Cancer Cases and Controls.
Jin Ho Chun, Chang Hee Lee, Sang Hwa Urm, Byung Chul Son, Jun Han Park, Kui Oak Jung, Chang Hak Sohn, Hye Kyoung Yoon, Choon Hee Son, Hyung In Kim, Jin Seok Kim
Korean J Prev Med. 1998;31(1):1-14.
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AbstractAbstract PDF
The genetically determined CYP2D6 activity is considered to be associated with cancer susceptibility with inter-individual variation. Genetic polymorphism of CYP2D6(B) and CYP2D6(T) was determined by the two polymerase chain reaction(PCR) and BstN1 and EcoN1 restriction fragment length polymorphisms(RFLP) for 67 lung cancer cases and 95 healthy volunteer controls. The cases were composed of 26 squamous cell carcinoma, 14 small cell carcinoma, 10 adenocarcinoma, 3 large cell undifferentiated carcinoma, and 14 not histologically diagnosed. The results were gained from the 142 subjects (57 cases and 85 controls) who observed successfully in two PCR and BstN1/EcoN1 RFLP. Only one and no mutant allele of the CYP2D6(B) and CYP2D6(T) gene was detected, that is, the frequency of mutant allele was very low; 0.7%(1/142) and 0%(0/142), respectively. Detected mutant allele of the CYP2D6(B) was heterozygous type(WM). The odds ratios for lung cancer susceptibility with CYP2D6(B) and CYP2D6(T) genotype were not calculated. These results are similar to the previous understanding that the mutant allele is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6(B) and CYP2D6(T) genotypes have maybe no association with lung cancer susceptibility in Koreans. This is the basic data of CYP2D6(B) and CYP2D6(T) genotypes for Koreans. It would be hepful for further study to determine lung cancer susceptibility of Koreans with the data about CYP1A1, CYP2E1, GSTM1 from future study.
Summary
Research Support, Non-U.S. Gov't
Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and N-acetyltransferase 2 Polymorphisms and the Risk of Gastric Cancer.
Su Hyung Hong, Jung Wan Kim, Ho Gak Kim, In Kyu Park, Jun Wook Ryoo, Chang Hyeong Lee, Yoon Kyung Sohn, Jong Young Lee
J Prev Med Public Health. 2006;39(2):135-140.
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AbstractAbstract PDF
OBJECTIVES
Polymorphisms of genes from glutathione Stransferases (GSTs) and N-acetyltransferase 2 (NAT2) have been associated with increased susceptibility to various cancers. Previous results showed that East Asians such as Koreans, Japanese and Chinese have a much higher frequency of the GSTM1 and GSTT1 null genotypes and NAT2 rapid acetylator type. Therefore, we investigated the association between the polymorphic types of GSTs (GSTM1, GSTT1, GSTP1) and NAT2 and the incidence of gastric cancer which is one of the most prevalent cancers among the East Asians. METHODS: It was performed in a case-control study consisting of 238 healthy subjects and 108 cancer patients (54 distal and 54 proximal carcinomas). We also evaluated the association between GSTs and NAT2 and the risk factors for gastric cancer such as alcohol consumption, smoking, H. pylori infection, family history of gastric cancer, and tumor location. RESULTS: In our study, the percentage of cases whose hometown was rural was higher than those of controls (odds ratio (OR) =2.88; 95% CI=1.72-4.76), and the frequency of the lower socio-economic status increased significantly in patients (OR=2.53; 95% CI=1.59-4.02). There was no significant difference in the GST polymorphic types between the cases and controls. However, NAT2 rapid or intermediate acetylator types were frequently detected in the cases with family history of gastric cancer (OR=1.92; 95% CI=1.79-26.0). CONCLUSIONS: These results suggest that the hometown and socio-economic status are important environmental factors for gastric carcinogenesis, and NAT2 polymorphic types could be associated with familial gastric carcinoma.
Summary
Comparative Study
Effects of Oxidative DNA Damage and Genetic Polymorphism of the Glutathion Peroxidase 1 (GPX1) and 8-Oxoguanine Glycosylase 1 (hOGG1) on Lung Cancer.
Chul Ho Lee, Kye Young Lee, Kang Hyeon Choe, Yun Chul Hong, Sung Il Noh, Sang Yong Eom, Young Jun Ko, Yan Wei Zhang, Dong Hyuk Yim, Jong Won Kang, Heon Kim, Yong Dae Kim
J Prev Med Public Health. 2006;39(2):130-134.
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AbstractAbstract PDF
OBJECTIVES
Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer. METHODS: Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. RESULTS: Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p<0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR=2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage. CONCLUSIONS: These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.
Summary

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