← Back to Search
Large-scale Investigation Of Base Excision Repair Genetic Polymorphisms And Lung Cancer Risk In A Multicenter Study.
R. Hung, P. Brennan, F. Canzian, N. Szeszenia-Dąbrowska, D. Zaridze, J. Lissowska, P. Rudnai, E. Fabianova, D. Mates, L. Forétova, V. Janout, V. Bencko, A. Chabrier, S. Borel, J. Hall, P. Boffetta
Published 2005 · Biology, Medicine
Download PDFAnalyze on Scholarcy
BACKGROUND Base excision repair (BER) is a highly conserved essential mechanism for maintaining genome integrity. We examined associations among four well-characterized polymorphisms of BER genes (OGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln) and lung cancer risk. METHODS A total of 2188 patients with lung cancer and 2198 control subjects without lung cancer recruited at 15 centers in six Eastern European countries from February 1998 to October 2002 provided DNA samples for genotype analysis. Genetic polymorphisms were analyzed by the fluorescence 5' exonuclease and Amplifluor assays. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We estimated the false-positive reporting probability (FPRP) for our results by incorporating a range of prior probabilities that specific polymorphisms are associated with lung cancer risk. All statistical tests were two-sided. RESULTS The overall odds ratio for lung cancer among those with the OGG1 Cys/Cys genotype compared with those with the OGG1 Ser/Ser genotype was 1.34 (95% CI = 0.95 to 1.88); the association was most prominent for adenocarcinoma risk (OR = 1.66, 95% CI = 1.04 to 2.66). Overall, the XRCC1 polymorphisms were not associated with the risk of lung cancer. However, the XRCC1 Arg194Trp and Arg280His variants were each associated with a reduced risk of lung cancer among subjects in the highest quartile of pack-years of smoking compared with common allele homozygotes (ORs of 0.65 [95% CI = 0.46 to 0.93] and 0.56 [95% CI = 0.36 to 0.86], respectively). The associations between the OGG1 Cys/Cys genotype and adenocarcinoma risk and between XRCC1 Arg194Trp polymorphism and lung cancer risk among heavy smokers remained robust given prior probabilities of 25% (FPRP = 0.238) and 10% (FPRP = 0.276), respectively. CONCLUSIONS Our results do not support a major independent role of BER gene polymorphisms in lung cancer risk. However, we cannot exclude the possibility that the OGG1 Ser326Cys and XRCC1 Arg194Trp polymorphisms play minor roles in lung carcinogenesis.
This paper references
Cancer incidence in five continents.
Freddie Ian Bray (1976)
Characterization of the hOGG1 promoter and its expression during the cell cycle.
A. Dhenaut (2000)
Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer amongmale smokers in Finland
R. Misra (2003)
Selection bias in the assessment of gene-environment interaction in case-control studies.
L. Morimoto (2003)
Haplotype Analysis in Population-based Association Studies
A. Mander (2001)
Excision of oxidatively damaged DNA bases by the human α-hOgg1 protein and the polymorphic α-hOgg1(Ser326Cys) protein which is frequently found in human populations
C. Dhérin (1999)
Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA
T. Kohno (1998)
Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population.
L. Excoffier (1995)
DNA repair activity for oxidative damage and risk of lung cancer.
T. Paz-Elizur (2003)
hOGG1 polymorphism and loss of heterozygosity (LOH): Significance for lung cancer susceptibility in a caucasian population
H. Wikman (2000)
8-Hydroxydeoxyguanosine in DNA from leukocytes of healthy adults: relationship with cigarette smoking, environmental tobacco smoke, alcohol and coffee consumption.
A. V. van Zeeland (1999)
Involvement of XRCC1 and DNA Ligase III Gene Products in DNA Base Excision Repair*
E. Cappelli (1997)
The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk.
A. Elahi (2002)
Association of the hOGG 1 Ser 326 Cys Polymorphism with Lung Cancer Risk 1
L. L. Marchand (2002)
Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer.
J. Park (2002)
Instability and decay of the primary structure of DNA
T. Lindahl (1993)
Tobacco smoke and involuntary smoking.
M. Alavanja (2004)
Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk.
Wei Zhou (2003)
Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption.
K. Sakumi (2003)
Polymorphisms in DNA repair genes and associations with cancer risk.
E. Goode (2002)
Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is frequently found in human populations.
C. Dhérin (1999)
The OGG1 gene encodes a repair enzyme for oxidatively damaged DNA and is involved in human carcinogenesis.
K. Shinmura (2001)
DNA damage and repair
Errol C. Friedberg (2003)
High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers.
M. Myakishev (2001)
Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk.
D. Ratnasinghe (2003)
Genetic susceptibility to lung cancer: the role of DNA damage and repair.
M. Spitz (2003)
HOGG1 Ser326Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese
T. Takezaki (2002)
Requirement for human AP endonuclease 1 for repair of 3'-blocking damage at DNA single-strand breaks induced by reactive oxygen species.
T. Izumi (2000)
A comparison of linkage disequilibrium measures for fine-scale mapping.
B. Devlin (1995)
Base excision repair of DNA in mammalian cells
H. Krokan (2000)
The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung.
K. Divine (2001)
Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review.
M. Berwick (2000)
From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity.
Y. Wang (2003)
Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.
S. Wacholder (2004)
Quality control by DNA repair.
T. Lindahl (1999)
DNA adduct levels and DNA repair polymorphisms in traffic‐exposed workers and a general population sample
D. Palli (2001)
A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defense mechanisms.
A. Besaratinia (2001)
Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells in vivo
山根 有人 (2004)
risk among African - Americans and Caucasians
KK Divine (2001)
XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency.
R. Lunn (1999)
Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes.
H. Mohrenweiser (2003)
Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity.
J. Tuimala (2002)
Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk.
H. Ito (2004)
hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.
H. Sugimura (1999)
DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326.
K. Janssen (2001)
Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland.
R. Misra (2003)
Cys polymorphism and modifi cation by environmental factors of stomach cancer risk in Chinese
S Chen (2002)
Lung Cancer Patients Have Increased 8‐Hydroxydeoxyguanosine Levels in Peripheral Lung Tissue DNA
Masaaki Inoue (1998)
Polymorphisms of the DNA repair gene XRCC1 and lung cancer risk.
D. Ratnasinghe (2001)
Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias.
S. Wacholder (2000)
XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects.
G. Matullo (2001)
A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung.
H. Ito (2002)
Repair of oxidative DNA damage
A. Lu (2007)
DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population.
S. Chen (2002)
Polymorphic variation in hOGG1 and risk of cancer: A review of the functional and epidemiologic literature
J. M. Weiss (2005)
Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians.
G. L. David-Beabes (2001)
Misclassification in case-control studies of gene-environment interactions: assessment of bias and sample size.
M. García-Closas (1999)
XRCC1 co-localizes and physically interacts with PCNA.
J. Fan (2004)
High-throughput single nucleotide polymorphism genotyping by fluorescent 5' exonuclease assay.
P. Morin (1999)
This paper is referenced by
DNA repair and cytotoxic drugs: the potential role of RAD51 in clinical outcome of non-small-cell lung cancer patients.
A. Nogueira (2013)
Gene polymorphisms of the DNA Repairing Genes APE 1 and XRCC 1 among Smoking Lung Cancer Egyptians
Rezk Ahmed Abd-ellateef Elbaz (2012)
Lung Cancer Risk and Genetic Polymorphisms in DNA Repair Pathways: A Meta-Analysis
C. Kiyohara (2010)
DNA Repair Gene Polymorphisms and Risk of Pancreatic Cancer
D. Li (2009)
XRCC1 polymorphisms, cooking oil fume and lung cancer in Chinese women nonsmokers.
M. Li (2008)
Lung Cancer: Genetics
M. Cote (2007)
DNA repair and cell cycle control genes and the risk of young-onset lung cancer.
S. Landi (2006)
Exposure to secondhand tobacco smoke and lung cancer by histological type: A pooled analysis of the International Lung Cancer Consortium (ILCCO)
Claire H. Kim (2014)
Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis
C. Kiyohara (2010)
DNA repair genotype and lung cancer risk in the beta-carotene and retinol efficacy trial.
J. Doherty (2013)
Development of an enzymatic DNA repair assay for molecular epidemiology studies: distribution of OGG activity in healthy individuals.
T. Paz-Elizur (2007)
Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of Northern Spain
M. Felicitas López-Cima (2007)
Molecular epidemiology to better predict lung cancer risk.
M. Reid (2008)
Cigarette Smoking and Lung Cancer: Modeling Total Exposure and Intensity
J. Lubin (2006)
DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.
G. Matullo (2006)
State of validation of biomarkers of carcinogen exposure and early effects and their applicability to molecular epidemiology.
P. Farmer (2007)
Dietary selenium intake, aldehyde dehydrogenase‐2 and X‐ray repair cross‐complementing 1 genetic polymorphisms, and the risk of esophageal squamous cell carcinoma
L. Cai (2006)
Meta-and Pooled Analyses Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer : A Pooled Analysis of Case-Control Studies
J. Lubin (2009)
Could 8-oxoguanine DNA glycosylase 1 Ser326Cys polymorphism be a biomarker of susceptibility in cancer?
B. Karahalil (2014)
The XRCC1 Arg280His polymorphism contributes to cancer susceptibility: an update by meta-analysis of 53 individual studies.
K. Zhang (2012)
Association of common polymorphisms in inflammatory genes with risk of developing cancers of the upper aerodigestive tract
Daniele Campa (2007)
International Lung Cancer Consortium: Pooled Analysis of Sequence Variants in DNA Repair and Cell Cycle Pathways
R. Hung (2008)
Lung Cancer in Never Smokers: Molecular Profiles and Therapeutic Implications
C. Rudin (2009)
hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type
T. Okasaka (2009)
Association of X-ray repair cross-complementing group 1 promoter rs3213245 polymorphism with lung cancer risk
R. Wang (2013)
Environmental Epidemiology , Present Chances and Challenges for Future
V. Bencko (2007)
Cigarette smoking and cancer: intensity patterns in the alpha-tocopherol, beta-carotene cancer prevention study in Finnish men.
J. Lubin (2008)
A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers.
S. Zienolddiny (2008)
Comet assay-based methods for measuring DNA repair in vitro; estimates of inter- and intra-individual variation
I. Gaivão (2007)
Effect of cruciferous vegetables on lung cancer in patients stratified by genetic status: a mendelian randomisation approach
P. Brennan (2005)
The role of genotype/phenotype at apurinic/apyrimidinic endonuclease Rs1130409 in renal cell carcinoma
Cheng-Hsi Liao (2020)
Association between the XRCC1 Arg194Trp polymorphism and risk of cancer: evidence from 201 case–control studies
Yan-zhong Feng (2014)See more