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Eun Jin Kim,
Kyung Mee Kim, Sun Ha Park,
Jong Sik Kim,
Won Kee Lee,
Sung Ick Cha,
Chang Ho Kim,
Young Mo Kang,
Sung Beom Han,
Tae Hoon Jung,
Jae Yong Park
[show abstract]
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ABSTRACT: The solute carrier family 11 member 1 (SLC11A1) protein plays important roles in macrophage activation and displays pleiotropic effects on various macrophage functions, including the regulation of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and oxidative burst. Considering the important roles of macrophage in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that the SLC11A1 gene may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, we first examined the frequencies of 12 candidate polymorphisms in the SLC11A1 gene in 27 healthy Korean individuals, and then genotyped 3 haplotype-tagging polymorphisms [IVS4 + 14G > C (rs3731865), D543 N (rs17235409), and (*)86A > G (rs1059823)] in 83 COPD patients and 203 healthy controls. Individuals with at least one variant allele of the D543 N and (*)86A > G polymorphisms were at a significantly increased risk for COPD compared with carriers with each homozygous wild-type allele [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) = 1.24-4.02, P = 0.007; and adjusted OR = 1.92, 95% CI = 1.10-3.35, P = 0.022, respectively]. Consistent with the findings of the genotyping analysis, the 122 haplotype carrying both the 543 N and (*)86G alleles was associated with a significantly increased risk for COPD compared with the 111 haplotype with the 542D and (*)86A alleles (adjusted OR = 2.05, 95% CI = 1.19-3.51, P = 0.009 and Bonferroni corrected P = 0.027). These findings suggest that the SLC11A1 polymorphisms could be used as markers for genetic susceptibility to COPD. However, further studies with large numbers of subjects are needed to confirm our findings.
Biochemical Genetics 08/2008; 46(7-8):506-19. · 0.86 Impact Factor
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Jong Myung Lee,
Yeh Rim Kang, Sun Ha Park,
Sung Ick Cha,
Jong Sik Kim,
Hyo Kyung Kang,
Won Kee Lee,
Min Jung Kim,
Chang Ho Kim,
Nung Soo Kim,
Tae Hoon Jung,
Jae Yong Park
[show abstract]
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ABSTRACT: Although several studies have evaluated the association between interleukin-1B (IL1B) polymorphisms and the risk of chronic obstructive pulmonary disease (COPD), most of these studies have focused on -511C-->T and -31T-->C polymorphisms, and the results of these studies have been inconsistent. This study was conducted to investigate the association between four potentially functional polymorphisms of the IL1B gene (-3737C-->T, -1464G-->C, -511C-->T, and -31T-->C) and the risk of COPD. In addition, we examined a potential interaction of the IL1B polymorphisms with the VNTR polymorphism of the IL-1 receptor antagonist (IL1RN) gene in determining the risk of COPD.
The IL1B and IL1RN genotypes were determined in 311 COPD patients and 386 healthy controls.
Individuals with at least one variant allele of the -511C-->T and -31T-->C polymorphisms were at a significantly increased risk for COPD when compared to carriers with each homozygous wild-type allele [adjusted odds ratio (OR) 1.53, 95% confidence interval (CI) 1.03-2.26, P=0.03; and adjusted OR 1.50, 95% CI 1.02-2.24, P=0.04, respectively]. When the COPD cases were stratified according to disease severity, the presence of at least one -511T and -31C alleles was significantly associated with severe COPD (adjusted OR 2.80, 95% CI 1.47-5.33, P=0.002; and adjusted OR 2.33, 95% CI 1.24-4.40, P=0.01, respectively), however, there was no significant association between the -511C-->T and -31T-->C genotypes and mild-to-moderate COPD. In addition, individuals carrying at least one IL1RN*2 allele were at a significantly lower risk for COPD compared to subjects carrying no IL1RN*2 allele (adjusted OR 0.51, 95% CI 0.26-0.98, P=0.04). In haplotype/diplotype analyses, individuals with one or two copies of the IL1B CCTC haplotype that carried the risk allele at all of the -3737C-->T, -1464G-->C, -511C-->T, and -31T-->C loci, were at a significantly increased risk of severe COPD when compared with subjects with zero copy of the CCTC haplotype (adjusted OR 1.96, 95% CI 1.16-3.29, P=0.01).
These findings suggest that polymorphisms in the IL1B and IL1RN genes might be useful markers for determining genetic susceptibility to COPD in a Korean population.
Respiratory Medicine 06/2008; 102(9):1311-20. · 2.47 Impact Factor
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Hee Jung Jun, Sun Ha Park,
Won Kee Lee,
Jin Eun Choi,
Jin Sung Jang,
Eun Jin Kim,
Sung Ick Cha,
Dong Sun Kim,
Sin Kam,
Chang Ho Kim,
Young Mo Kang,
Tae Hoon Jung,
Jae Yong Park
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ABSTRACT: p73, a structural and functional homologue of p53, plays an important role in modulating cell-cycle control and apoptosis. MDM2 represses the transcriptional activity of p73 and thus attenuates its activity. Based on the interaction between p73 and MDM2 in cell-cycle control and apoptosis, we investigated the association between p73 G4C14-to-A4T14 and MDM2 309T > G polymorphisms, alone and in combination, on the risk of lung cancer in a Korean population. The p73 and MDM2 genotypes were determined in 582 lung cancer patients and in 582 healthy control subjects who were frequency-matched for age and gender. The p73 AT/AT and MDM2 309 GG genotypes were associated with a nonsignificant increased risk of lung cancer (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.83-2.24; and adjusted OR = 1.29, 95% CI = 0.92-1.80, respectively), compared with their wild-type genotypes, respectively. When the p73 and MDM2 polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of variant alleles increased (Ptrend = 0.01). Subjects with three or four variant alleles were at a significantly increased risk of lung cancer (adjusted OR = 1.74, 95% CI = 1.11-2.74, P = 0.02) compared to subjects with zero variant allele. These results suggest an additive effect of the p73 and MDM2 variant alleles on an increased risk of lung cancer.
Molecular Carcinogenesis 02/2007; 46(2):100-5. · 3.16 Impact Factor
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Jin Eun Choi, Sun Ha Park,
Kyung Mee Kim,
Won Kee Lee,
Sin Kam,
Sung Ick Cha,
Chang Ho Kim,
Young Mo Kang,
Young-Chul Kim,
Sung Beom Han,
Tae Hoon Jung,
Jae Yong Park
[show abstract]
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ABSTRACT: Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population.
We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls.
Of the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P = 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45-0.88, P = 0.007). When the analyses were stratified by smoking status, the protective effect of the TT genotype was statistically significant in ever-smokers (adjusted OR = 0.59, 95% CI = 0.41-0.86, P = 0.007), but not in never-smokers (adjusted OR = 0.89, 95% CI = 0.45-1.75, P = 0.73; P = 0.08, test for homogeneity). Consistent with the results of the genotyping analysis, the CGGCT haplotype with the 181946C allele was associated with a significantly increased risk of lung cancer compared to the CGGTT haplotype carrying the 181946T allele (adjusted OR = 1.50, 95% CI = 1.09-2.07, P = 0.012 and Bonferroni corrected P-value = 0.048).
These results suggest that the EGFR polymorphisms, particularly the 181945C>T polymorphism, could be used as markers for the genetic susceptibility to lung cancer.
BMC Cancer 01/2007; 7:199. · 3.01 Impact Factor
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Sun Ha Park,
Jin Eun Choi,
Eun Jin Kim,
Jin Sung Jang,
Won Kee Lee,
Sung Ick Cha,
Chang Ho Kim,
Sin Kam,
Dong Sun Kim,
Rang-Woon Park,
Young-Chul Kim,
Sung Beom Han,
Tae Hoon Jung,
Jae Yong Park
[show abstract]
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ABSTRACT: The FAS and FASL system play an important role in regulating extrinsic apoptotic pathway and inappropriate regulation of this signaling pathway contributes to lung tumorigenesis. Polymorphisms in the promoter region of the FAS (-1377G>A and -670A>G) and FASL (-844C>T) have been shown to alter the transcriptional activities of these genes. In order to evaluate the contribution of these polymorphisms to the risk of lung cancer, we carried out a case-control study in a Korean population.
The FAS and FASL genotypes were determined in 582 lung cancer patients and 582 healthy control subjects who were frequency-matched for age and gender.
The FAS and FASL genotypes and the FAS haplotypes exhibited no apparent relationship with the risk of lung cancer. In addition, there was no significant interaction between the FAS and FASL polymorphisms in the development of lung cancer.
These results suggest that the FAS-1377G>A and -670A>G and FASL-844C>T polymorphisms do not significantly affect the susceptibility to lung cancer in Koreans.
Lung Cancer 12/2006; 54(3):303-8. · 3.43 Impact Factor
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ABSTRACT: The MDM2 protein plays an important role in regulating cell proliferation and apoptosis by interaction with multiple proteins including p53 and Rb. A polymorphism (309T>G) in the MDM2 promoter has been shown to result in higher levels of MDM2 RNA and protein. In order to evaluate the association of the MDM2 309T>G polymorphism and lung cancer risk, we carried out a case-control study in a Korean population.
The MDM2 genotypes were determined in 582 lung cancer patients and in 582 healthy control subjects who were frequency matched for age and gender.
The distribution of the MDM2 309T>G genotypes was not significantly different between overall lung cancer cases and controls. However, when the cases were categorized by tumor histology, the 309GG genotype was associated with a significantly increased risk of adenocarcinoma (adjusted OR=1.91, 95% CI=1.16-3.14, P=0.01) compared to the 309TT genotype. In addition, the risk of adenocarcinoma increased as the number of 309G alleles increased (P(trend)=0.01).
Our findings suggest that the MDM2 309T>G polymorphism may be used as a marker for genetic susceptibility to adenocarcinoma of the lung.
Lung Cancer 10/2006; 54(1):19-24. · 3.43 Impact Factor
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Su Jeong Lee,
Sin Yeob Lee,
Hyo-Sung Jeon, Sun Ha Park,
Jin Sung Jang,
Ga Young Lee,
Ji Woong Son,
Chang Ho Kim,
Won Kee Lee,
Sin Kam,
Rang Woon Park,
Tae-In Park,
Young Mo Kang,
In-San Kim,
Tae Hoon Jung,
Jae Yong Park
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ABSTRACT: Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.
Cancer Epidemiology Biomarkers & Prevention 03/2005; 14(3):571-5. · 4.12 Impact Factor
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Su Jeong Lee,
Hyo-Sung Jeon,
Jin-Sung Jang, Sun Ha Park,
Ga Young Lee,
Byung-Heon Lee,
Chang Ho Kim,
Young Mo Kang,
Won Kee Lee,
Sin Kam,
Rang Woon Park,
In-San Kim,
Young Lae Cho,
Tae Hoon Jung,
Jae Yong Park
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ABSTRACT: DNA-methyltransferase-3B (DNMT3B) plays an important role in the generation of aberrant methylation in carcinogenesis. Polymorphisms and haplotypes of the DNMT3B gene may influence DNMT3B activity on DNA methylation, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we investigated the association of the -283T > C (from exon 1A transcription start site) and -579G > T (from exon 1B transcription start site) polymorphisms in DNMT3B promoter, and their haplotypes with the risk of lung cancer in a Korean population. The DNMT3B genotype was determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and sex. Individuals with at least one -283T allele were at a significantly decreased risk of adenocarcinoma (AC) and small cell carcinoma (SM) [adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.28-0.82, P = 0.007; and adjusted OR = 0.47, 95% CI = 0.24-0.93, P = 0.03, respectively] compared with those harboring a -283CC genotype. Individuals with at least one -579G allele were also at a significantly decreased risk of AC and SM (adjusted OR = 0.47, 95% CI = 0.28-0.81, P = 0.006; and adjusted OR = 0.51, 95% CI = 0.26-0.99, P = 0.048, respectively) compared with those having a -579TT genotype. The -283T allele was linked with the -579G allele, and haplotype -283T/-579G was associated with a significantly decreased risk of AC (adjusted OR = 0.48, 95% CI = 0.29-0.81, P = 0.006) as compared with haplotype -283C/-579T. In a promoter assay, carriage of the -283T allele showed a significantly lower promoter activity ( approximately 50%) compared with the -283C allele (P < 0.001), but the -579G > T polymorphism did not have an affect on the DNMT3B promoter activity. These results suggest that the DNMT3B -283T > C polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to lung cancer.
Carcinogenesis 02/2005; 26(2):403-9. · 5.70 Impact Factor
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Sun Ha Park,
Ga Young Lee,
Hyo-Sung Jeon,
Su Jeong Lee,
Kyung Mee Kim,
Sang Soo Jang,
Chang Ho Kim,
Won Kee Lee,
Sin Kam,
Rang Woon Park,
In-San Kim,
Tae Hoon Jung,
Jae Yong Park
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ABSTRACT: Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the -93G-->A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 -93G-->A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 -93G-->A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR=2.02; 95% CI=1.15-3.55; p=0.014) and the combined GG and GA genotype (adjusted OR=1.83; 95% CI=1.24-2.71; p=0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (< or = 39 pack-years; adjusted OR=1.95; 95% CI=1.03-3.66; p=0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (> 39 pack-years; adjusted OR=1.47; 95% CI=0.82-2.61). These results suggest that the hMLH1 -93G-->A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.
International Journal of Cancer 12/2004; 112(4):678-82. · 5.44 Impact Factor
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Hyo-Sung Jeon,
Kyung Mee Kim, Sun Ha Park,
Su Yeon Lee,
Jin Eun Choi,
Ga Young Lee,
Sin Kam,
Rang Woon Park,
In-San Kim,
Chang Ho Kim,
Tae Hoon Jung,
Jae Yong Park
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ABSTRACT: DNA repair plays a critical role in protecting the genome from insults of cancer-causing agents, such as those found in tobacco smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related cancers. Recently, several polymorphisms have been identified in the xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of lung cancer. The study population consisted of 310 lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined His/His and His/Asp genotype was used as the reference. The protective effect of the Asp/Asp genotype against lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the lung cancers were analyzed by histologic type, the Asp/Asp genotype was associated with a significantly decreased risk of squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG codon 1104 polymorphism contributes to genetic susceptibility to lung cancer.
Carcinogenesis 11/2003; 24(10):1677-81. · 5.70 Impact Factor
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Jin Eun Choi, Sun Ha Park,
Hyo-Sung Jeon,
Kyung Mee Kim,
Ga Young Lee,
Rang Woon Park,
Sin Kam,
In-San Kim,
Chang Ho Kim,
Sang Hoon Jheon,
Tae Hoon Jung,
Jae Yong Park
Cancer Epidemiology Biomarkers & Prevention 10/2003; 12(9):947-9. · 4.12 Impact Factor
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[show abstract]
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ABSTRACT: In Down syndrome, the incidence of solid tumors including lung cancer is considerably lower than that of the general population. The low risk of lung cancer in individuals with Down syndrome may be related to the gene-dosage effect of the extra chromosome 21. It may suggest that tumor suppressor genes playing a role in the pathogenesis of lung cancer may be present on chromosome 21.
A total of 39 surgically resected non-small cell lung cancers were analyzed using nine microsatellite markers for 21q. Loss of heterozygosity was considered to be present when the signal intensity of the allele in tumor DNA was less than 50% of that in the corresponding normal DNA.
Loss of heterozygosity for at least one locus was detected in 22 of 39 tumors (56.4%). Allelic loss was frequently detected at three distinct regions: at the locus D21S1432 on 21q21.1, the region between D21S1435 and D21S1442 on 21q21.2 to 21.3, and the region between D21S1270 and D21S1445 on 21q22.1.
These results indicate that loss of heterozygosity on 21q may play an important role in the pathogenesis of non-small cell lung cancer.
The Annals of Thoracic Surgery 06/2003; 75(5):1597-600. · 3.74 Impact Factor
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Jae Yong Park,
Su Yeon Lee,
Hyo-Sung Jeon, Sun Ha Park,
Nack Chun Bae,
Eung Bae Lee,
Sung Ick Cha,
Jae-Ho Park,
Sin Kam,
In-San Kim,
Tae Hoon Jung
Lung Cancer 05/2002; 36(1):15-6. · 3.43 Impact Factor
