Journal of Preventive Medicine and Public Health

Original Articles

Association Between MicroRNA196a2 rs11614913 Genotypes and the Risk of Non-Small Cell Lung Cancer in Korean Population: Young-Seoub Hong, Ho-Jin Kang, Jong-Young Kwak, Byung Lae Park, Chang-Hun You, Yu-Mi Kim, Heon Kim; J Prev Med Public Health. 2011;44(3):125-130. Published online May 17, 2010; DOI: https://doi.org/10.3961/jpmph.2011.44.3.125

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Objectives

The microRNA (miRNA) miR-196a2 may play an important role in lung cancer development and survival by altering binding activity of target mRNA. In this study, we evaluated their associations with the susceptibility of non-small cell lung cancers (NSCLC) by case-control study in a Korean population.

Methods

We performed genotyping analyses for miR-196a2 rs11614913 T/C at miRNA regions in a case-control study using blood samples of 406 NSCLC patient and 428 cancer-free control groups.

Results

The total C allele frequencies for miR-196a2 were 48.8% for the patients and 45.6% for the controls; and the genotype frequencies of TT, TC, and CC were 23.7%, 55.2%, and 21.1% for the patients and 31.1%, 46.35%, and 22.4% for the controls (p<0.05). Participants who possesses TC/CC genotypes showed high risk for NSCLC compared to those possessed TT genotypes (OR, 1.42; 95% CI, 1.03 to 1.96). The association was persisted in 60 and older age group, male, smokers, those without family history for cancer. However, no significant association of CC genotypes in recessive genetic model was observed.

Conclusions

In conclusion, this case-control study provides evidence that miR-196a2 rs11614913 C/T polymorphisms are associated with a significantly increased risk of NSCLC in a dominant model, indicating that common genetic polymorphisms in miR-196a2 rs11614913 are associated with NSCLC. The association of miR196a2 rs11614913 polymorphisms and NSCLC risk require confirmation through additional larger studies.

Summary

Citations

Citations to this article as recorded by

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Effect of miR-196a2 rs11614913 Polymorphism on Cancer Susceptibility: Evidence From an Updated Meta-Analysis
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Authors’ reply to Jayaraj et al. ‘s Letter to the Editor re: MIR196A2 rs11614913 contributes to susceptibility to colorectal cancer in Iranian population: A multi-center case-control study and meta-analysis
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The Molecular Analysis of rs11614913 Polymorphism from miRNA196a Gene and Its Relationship with TNF-α Gene Expression in Cervical Cancer
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Association of mir-196a-2 rs11614913 and mir-149 rs2292832 Polymorphisms With Risk of Cancer: An Updated Meta-Analysis
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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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Abstract 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

English Abstracts

Apolipoprotein E Polymorphism and Cognitive Function Change of the Elderly in a Rural Area, Korea.: Sang Kyu Kim, Tae Yoon Hwang, Kyeong Soo Lee, Pock Soo Kang, Hee Soon Cho, Young Kyung Bae; J Prev Med Public Health. 2009;42(4):261-266.; DOI: https://doi.org/10.3961/jpmph.2009.42.4.261

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Abstract PDF

OBJECTIVES
The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. METHODS: Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. RESULTS: The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. CONCLUSIONS: The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.

Summary

Citations

Citations to this article as recorded by

ApoE Type 4 Allele Affects Cognitive Function of Aged Population in Tianjin City, China
Shoudan Sun, Jingming Fu, Jun Chen, Wei Pang, Ruomei Hu, Haiqiang Li, Long Tan, Yugang Jiang
American Journal of Alzheimer's Disease & Other Dementiasr.2015; 30(5): 503. CrossRef

High Throughput Genotyping for Genomic Cohort Study.: Woong Yang Park; J Prev Med Public Health. 2007;40(2):102-107.; DOI: https://doi.org/10.3961/jpmph.2007.40.2.102

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Abstract PDF

Human Genome Project (HGP) could unveil the secrets of human being by a long script of genetic codes, which enabled us to get access to mine the cause of diseases more efficiently. Two wheels for HGP, bioinformatics and high throughput technology are essential techniques for the genomic medicine. While microarray platforms are still evolving, we can screen more than 500,000 genotypes at once. Even we can sequence the whole genome of an organism within a day. Because the future medicne will focus on the genetic susceptibility of individuals, we need to find genetic variations of each person by efficient genotyping methods.

Summary

Citations

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Journal of Veterinary Diagnostic Investigation.2009; 21(5): 623. CrossRef

Original Articles

Specimen Storage and Analysis for Genomic Epidemiology.: Yun Chul Hong, Kwan Hee Lee; Korean J Prev Med. 2003;36(3):209-212.

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Abstract PDF: Because of advances of technologies in the field of genomic epidemiology in the recent years, specimen collection, storage and analysis became an essential part of research methodologies. DNA is now being used in epidemiologic studies to evaluate genetic risk factors and specimens other than the fresh whole blood can be used for PCR. Therefore, All nucleated cells, such as buccal swabs and urine specimens, are suitable for DNA analysis. For an unlimited source of genomic DNA, EBV transformation of lymphocytes can be used for immortalization. However, the type of specimen collected in genomic epidemiologic studies will depend on the study where the epidemiologist play a leading role for the design. We also briefly described various kinds of analysis for SNP that is an essential part of the genomic epidemiology.; 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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Abstract PDF: 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

A Case-Control Study on Effects of Genetic Polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 on Risk of Lung Cancer.: Hong Mei Nan, Heon Kim, Jong Won Kang, Jang Whan Bae, Kang Hyeon Choe, Ki Hyeong Lee, Seung Taik Kim, Choong Hee Won, Yong Min Kim; Korean J Prev Med. 1999;32(2):123-129.

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Abstract PDF: OBJECTIVES
This study was performed to investigate effects of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytochrome P450 2E1 (CYP2E1) on lung cancer development. METHODS: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital from March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung cancer were statistically analyzed. RESULTS: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls OR:1.43(0.81-2.51). The frequencies of Ile/Ile, Ile/Val and Val/Val of the CYP1A1 polymorphisms were 59.18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 (x2trend=0.253, p-value>0.05). The respective frequency of c1/c1, c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls (x2trend=5.783, p<0.05). c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% CI) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only smoking habit came out to be a significant risk factor for lung cancer. CONCLUSION: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking.; 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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Abstract 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

English Abstract

The Relationship between ACE I/D Polymorphism and HDL Cholesterol.: Chang Hun You, Young Seoub Hong, Jong Young Kwak, Na Young Kim, Mee Sook Roh, Kap Yeol Jung, Yong Hwan Lee, Jung Man Kim, Joon Youn Kim; J Prev Med Public Health. 2006;39(6):505-510.

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Abstract PDF: OBJECTIVES
The purpose of this study is to evaluate the association of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with cardiovascular disease risk factors. METHODS: Out of a total of 608 middle-aged adults who visited local health centers, 424 subjects (104 male, 320 female) who had not been diagnosed with hypertension, diabetes mellitus, or hyperlipidemia were included in this study. ACE genotypes were determined in all subjects by polymerase chain reaction methods. RESULTS: Statistical differences in high-density lipoprotein (HDL) cholesterol levels according to ACE genotype were observed using ANOVA (p<0.05), but no differences were found in other cardiovascular risk factors. Specifically, men with the DD and DI genotypes had significantly lower HDL cholesterol levels than those with the II genotype based on the LSD multi-comparison test (p<0.05). CONCLUSIONS: In men, the D-allele of the ACE I/D polymorphism was significantly associated with reduced HDL cholesterol levels. In the future, larger studies are needed to confirm this relationship between ACE I/D polymorphism and HDL cholesterol.; 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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Abstract 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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Abstract 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

English Abstract

Folate and Homocysteine Levels during Pregnancy affect DNA Methylation in Human Placenta.: Bo hyun Park, Young Ju Kim, Jong soon Park, Hwa young Lee, Eun hee Ha, Jung won Min, Hye sook Park; J Prev Med Public Health. 2005;38(4):437-442.

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Abstract PDF: OBJECTIVES
DNA methylation is one of the best characterized epigenetic mechanisms that play a regulatory role in genome programming and imprinting during embryogenesis. In this present study, we investigated the association between DNA methylation in the human placenta and the maternal folate and homocysteine concentrations on the Methylenetetrahydrofolatereductase (MTHFR) genetic polymorphism during pregnancy. METHODS: We investigated 107 pregnant women who visited Ewha Woman's University Hospital for prenatal care during their 24~28 weeks-period of gestation. During the second trimester, we measured the serum homocysteine and folate concentrations. The MTHFR 677 genetic polymorphism was determine by performing PCR-RFLP assay. The expression of DNA methylation in the human placentas was estimated by using immunohistochemistry method. RESULTS: Serum folate was negatively correlated with the serum homocysteine concentration for all the MTHFR genotypes. We found positive correlation between the folate concentrations and the DNA methylation in the human placenta (p< 0.05). An increasing concentration of homocysteine was associated with reduced DNA methylation in the human placenta. The coefficient value was -2.03 (-3.77, -0.29) on the regression model (p< 0.05). CONCLUSION: These findings suggest that the maternal folate and homocysteine levels along with the MTHFR 677 genetic polymorphism during pregnancy affect the DNA methylation in the human placenta.; Summary

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