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dc.contributor.authorChae, Myung Hwa
dc.contributor.authorJang, Jin-Sung
dc.contributor.authorKang, Hyo-Gyoung
dc.contributor.authorPark, Jae Hyung
dc.contributor.authorPark, Jung Min
dc.contributor.authorLee, Won Kee
dc.contributor.authorKam, Sin
dc.contributor.authorLee, Eung Bae
dc.contributor.authorSon, Ji-Woong
dc.contributor.authorPark, Jae Yong
dc.date.accessioned2009-03-27T08:27:37Z
dc.date.available2009-03-27T08:27:37Z
dc.date.issued2006-04
dc.identifier.citationMol. Carcinog. 2006, 45 (4):239-249en
dc.identifier.issn0899-1987
dc.identifier.pmid16385589
dc.identifier.doi10.1002/mc.20171
dc.identifier.urihttp://hdl.handle.net/10146/57456
dc.descriptionBiomarkers of individual susceptibility: field studiesBiomarker (including alleles if genetic): AGT polymorphisms (485C>A, Leu53Leu (C>T) and Leu84Phe]Effect studied (phenotype/pathology): lung cancerMethod of analysis: PCR-RFLPStudy design: case-control Study size: 432 lung cancer patients and 432 healthy controlsImpact on outcome (including dose-response):The 485 AA genotype was associated with a significantly increased risk for overall lung cancer as compared with the 485 CC genotype and the combined 485 CCώCA genotype, respectively (adjusted OR=1.83, 95% CI=1.12- 2.99, P=0.02, and Bonferroni corrected P-value, Pc=0.04; and adjusted OR=1.67, 95% CI=1.05- 2.66, P=0.03, respectively).Quality control: performed in triplicates. KEYWORDS CLASSIFICATION: Adenocarcinoma;Adult;biomarkers of individual susceptibility: field studies;cancer epidemiology;Carcinoma,Large Cell;Carcinoma,Small Cell;Carcinoma,Squamous Cell;Case-Control Studies;DNA Damage;DNA Repair;enzymology;Female;genetics;Genetic Predisposition to Disease;Genotype;Humans;Korea;Lung Neoplasms;metabolism;Male;mechanisms of carcinogenesis;O(6)-Methylguanine-DNA Methyltransferase;pathology;Polymorphism,Genetic;Promoter Regions (Genetics);Research;Risk Factors;secondary;field studies;genetic;analysis.en
dc.description.abstractO6-alkylguanine-DNA alkyltransferase (AGT) plays an important role in the repair of O6-alkylguanine adducts, which are major mutagenic lesions produced by environmental carcinogens. Polymorphisms in the AGT gene may affect the capacity to repair DNA damage and thereby have influence on individual's susceptibility to smoking-related cancer. To test this hypothesis, we investigated the potential association of AGT polymorphisms (485C > A, Leu53Leu (C > T) and Leu84Phe] with the risk of lung cancer in a Korean population. The AGT genotypes were determined in 432 lung cancer patients and in 432 healthy controls who were frequency-matched for age and gender. The 485 AA genotype was associated with a significantly increased risk for overall lung cancer as compared with the 485 CC genotype and the combined 485 CC + CA genotype, respectively (adjusted odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.12-2.99, P = 0.02, and Bonferroni corrected P-value (Pc) = 0.04; and adjusted OR = 1.67, 95% CI = 1.05-2.66, P = 0.03, respectively). When the lung cancer cases were categorized by the tumor histology, the 485 AA genotype was associated with a significantly increased risk of adenocarcinoma (AC) and small cell carcinoma (SmCC), respectively, as compared with the combined 485 CC + CA genotype (adjusted OR = 2.54, 95% CI = 1.39-4.66, P = 0.003; and adjusted OR = 2.19, 95% CI = 1.06-4.55, P = 0.04, respectively). However, the genotype distributions of the Leu53Leu and Leu84Phe polymorphisms were not significantly different between the lung cancer cases and the controls. On a promoter assay, the 485C > A polymorphism did not have an effect on the promoter activity of the AGT gene. These results suggest that the effect of the AGT 485C > A polymorphism on the risk of lung cancer may be secondary to linkage disequilibrium (LD) with either another AGT variant or with a true susceptibility gene, and that the AGT 485C > A polymorphism could be used as a marker for the genetic susceptibility to lung cancer.
dc.language.isoenen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/112223526/abstracten
dc.subjectO6-alkylguanine-DNA alkyltransferaseen
dc.subjectLung canceren
dc.subjectGenetic susceptibilityen
dc.subject.meshAdenocarcinoma
dc.subject.meshAdult
dc.subject.meshCarcinoma, Large Cell
dc.subject.meshCarcinoma, Small Cell
dc.subject.meshCarcinoma, Squamous Cell
dc.subject.meshCase-Control Studies
dc.subject.meshDNA Damage
dc.subject.meshDNA Repair
dc.subject.meshFemale
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenotype
dc.subject.meshHumans
dc.subject.meshLung Neoplasms
dc.subject.meshMale
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshPolymorphism, Genetic
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshRisk Factors
dc.titleO6-alkylguanine-DNA alkyltransferase gene polymorphisms and the risk of primary lung cancer.en
dc.typeArticleen
dc.identifier.journalMolecular carcinogenesisen
html.description.abstractO6-alkylguanine-DNA alkyltransferase (AGT) plays an important role in the repair of O6-alkylguanine adducts, which are major mutagenic lesions produced by environmental carcinogens. Polymorphisms in the AGT gene may affect the capacity to repair DNA damage and thereby have influence on individual's susceptibility to smoking-related cancer. To test this hypothesis, we investigated the potential association of AGT polymorphisms (485C > A, Leu53Leu (C > T) and Leu84Phe] with the risk of lung cancer in a Korean population. The AGT genotypes were determined in 432 lung cancer patients and in 432 healthy controls who were frequency-matched for age and gender. The 485 AA genotype was associated with a significantly increased risk for overall lung cancer as compared with the 485 CC genotype and the combined 485 CC + CA genotype, respectively (adjusted odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.12-2.99, P = 0.02, and Bonferroni corrected P-value (Pc) = 0.04; and adjusted OR = 1.67, 95% CI = 1.05-2.66, P = 0.03, respectively). When the lung cancer cases were categorized by the tumor histology, the 485 AA genotype was associated with a significantly increased risk of adenocarcinoma (AC) and small cell carcinoma (SmCC), respectively, as compared with the combined 485 CC + CA genotype (adjusted OR = 2.54, 95% CI = 1.39-4.66, P = 0.003; and adjusted OR = 2.19, 95% CI = 1.06-4.55, P = 0.04, respectively). However, the genotype distributions of the Leu53Leu and Leu84Phe polymorphisms were not significantly different between the lung cancer cases and the controls. On a promoter assay, the 485C > A polymorphism did not have an effect on the promoter activity of the AGT gene. These results suggest that the effect of the AGT 485C > A polymorphism on the risk of lung cancer may be secondary to linkage disequilibrium (LD) with either another AGT variant or with a true susceptibility gene, and that the AGT 485C > A polymorphism could be used as a marker for the genetic susceptibility to lung cancer.


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