← Back to Search
Repair Of Tobacco Carcinogen-induced DNA Adducts And Lung Cancer Risk: A Molecular Epidemiologic Study.
Q. Wei, L. Cheng, C. Amos, L. Wang, Z. Guo, W. Hong, M. Spitz
Published 2000 · Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
BACKGROUND Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. METHODS From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case-control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. RESULTS Overall, lower DRC was observed in case patients than in control subjects (P:<.001) and was associated with a greater than twofold increased risk of lung cancer. Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1-3.1, OR = 2.0 with 95% CI = 1.2-3.4, and OR = 4. 3 with 95% CI = 2.6-7.2 for the second, third, and fourth quartiles, respectively; P:(trend)<.001). Case patients who were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. CONCLUSION The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case-control study should be validated in prospective studies.
This paper references
Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung.
J. Wiencke (1995)
Comparison of pulmonary DNA adduct levels, measured by 32P-postlabelling and aryl hydrocarbon hydroxylase activity in lung parenchyma of smokers and ex-smokers.
O. Geneste (1991)
Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations.
S. V. Vulimiri (2000)
Reduced DNA repair capacity in head and neck cancer patients.
L. Cheng (1998)
DNA repair in humans.
A. Sancar (1995)
Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients.
D. Ryberg (1994)
Brown for assistance in preparing the manuscript
Joanne Sider (2000)
Differences in lung cancer risk between men and women: examination of the evidence.
E. Zang (1996)
Reduced DNA repair synthesis in healthy women having first degree relatives with breast cancer.
E. Kovacs (1987)
Microsatellite instability: marker of a mutator phenotype in cancer.
L. Loeb (1994)
Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type.
H. Risch (1993)
Increased familial risk for non-lung cancer among relatives of lung cancer patients.
T. A. Sellers (1987)
DNA adducts, protein adducts, and sister chromatid exchange in cigarette smokers and nonsmokers.
F. Perera (1987)
Proliferating cell nuclear antigen is required for DNA excision repair
Mahmud K. K. Shivji (1992)
Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53
M. Denissenko (1996)
Mismatch repair: mechanisms and relationship to cancer susceptibility.
R. Kolodner (1995)
Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer.
S. P. Shriver (2000)
Fifty years of benzo(a)pyrene
D. Phillips (1983)
Reduced DNA repair capacity in lung cancer patients.
Q. Wei (1996)
Differences and similarities in the repair of two benzo[a]pyrene diol epoxide isomers induced DNA adducts by uvrA, uvrB, and uvrC gene products.
M. S. Tang (1992)
Development and field-test validation of an assay for DNA repair in circulating human lymphocytes.
W. C. Athas (1991)
linear and supercoiled DNA
RB Everson (1986)
Benzo(a)pyrene diol epoxide-induced chromosomal aberrations and risk of lung cancer.
Q. Wei (1996)
DNA repair synthesis in individuals with and without a family history of cancer.
R. Pero (1989)
Benzo[alpha]pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes.
H. Gelboin (1980)
Molecular epidemiology of human cancer risk: gene–environment interactions and p53 mutation spectrum in human lung cancer
W. P. Bennett (1999)
Deficient nucleotide excision repair activity in protein extracts from normal human lymphocytes.
J. M. Barret (1995)
Slow repair of bulky DNA adducts along the nontranscribed strand of the human p53 gene may explain the strand bias of transversion mutations in cancers
M. Denissenko (1998)
Interactions of benzo(a)pyrene diol-epoxides with linear and supercoiled DNA.
M. Macleod (1985)
Reduced expression of hMLH1 and hGTBP/hMSH6: a risk factor for head and neck cancer.
Q. Wei (1998)
DNA repair and aging in basal cell carcinoma: a molecular epidemiology study.
Q. Wei (1993)
Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers.
D. Tang (1998)
Contribution of genetic and nutritional factors to DNA damage in heavy smokers.
L. Mooney (1997)
Correlates of plasma cortisol and DNA repair in human peripheral lymphocytes: suppression of repair in women taking estrogen.
S. O'brien (1993)
Enchancement of the infectivity of simian virus 40 deoxyribonucleic acid with diethylaminoethyl-dextran.
J. H. McCutchan (1968)
Detection of smoking-related covalent DNA adducts in human placenta.
R. Everson (1986)
DNA repair and epidemiology of basal cell carcinoma.
Larry Grossman (1995)
p53 mutations in human cancers.
M. Hollstein (1991)
Powerful and versatile enhancer-promoter unit for mammalian expression vectors.
M. K. Foecking (1986)
Effects of genetic polymorphism of metabolic enzymes, nutrition, and lifestyle factors on DNA adduct formation in lymphocytes.
Y. Wang (1998)
Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts.
R. Chen (1992)
Fluorescence in situ hybridization method for measuring transfection efficiency.
L. Cheng (1996)
Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans.
M. Shen (1998)
Inactivation of plasmid reporter gene expression by one benzo(a)pyrene diol-epoxide DNA adduct in adult rat hepatocytes.
K. Koch (1993)
What are the odds that smoking will kill you?
M. Mattson (1987)
Identifying and recruiting healthy control subjects from a managed care organization: a methodology for molecular epidemiological case-control studies of cancer.
K. Hudmon (1997)
The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm.
K. Kraemer (1994)
Relevance of metabolic polymorphisms to human carcinogenesis: evaluation of epidemiologic evidence.
N. Caporaso (1991)
Evidence for mendelian inheritance in the pathogenesis of lung cancer.
T. A. Sellers (1990)
Benzo[a]pyrene diolepoxide-DNA adducts in alveolar macrophages of smokers.
A. Izzotti (1991)
In vitro induction of benzo(a)pyrene diol epoxide-DNA adducts in peripheral lymphocytes as a susceptibility marker for human lung cancer.
D. Li (1996)
Effect of aging on DNA repair and skin carcinogenesis: a minireview of population-based studies.
Q. Wei (1998)
Relationship between excision repair and the cytotoxic and mutagenic effect of the 'anti' 7,8-diol-9,10-epoxide of benzo[a]pyrene in human cells.
L. Yang (1982)
Enhancement of DNA repair in human skin cells by thymidine dinucleotides: evidence for a p53-mediated mammalian SOS response.
M. Eller (1997)
DNA Adducfs, Protein Adducts, and Sister Chromatid Exchange in Cigarette Smokers and Nonsmokers
F. Perera (1987)
This paper is referenced by
Te-Chun Shen (2019)
Gender differences in lung cancer: have we really come a long way, baby?
J. Olak (2004)
XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report.
P. Mehta (2006)
Lung cancer in women: exploring sex differences in susceptibility, biology, and therapeutic response.
J. Donington (2006)
[Tobacco and morphology: pulmonary diseases].
L. Carvalho (2007)
Lung cancer in women: differences in epidemiology, biology, histology, and treatment outcomes.
M. Rivera (2013)
olymorphisms in excision repair ross-complementing group 4 ( ERCC 4 ) and usceptibility to primary lung cancer in a Chinese an population
inhua Shaoa (2008)
Dietary magnesium and DNA repair capacity as risk factors for lung cancer.
S. Mahabir (2008)
Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis
C. Kiyohara (2010)
Polymorphisms in ERCC 1 and Grade 3 or 4 Toxicity in Non – Small Cell Lung Cancer Patients
R. Suk (2005)
p73 G4C14-A4T14 polymorphism and cancer risk: a meta-analysis based on 27 case-control studies.
F. Liu (2011)
Docetaxel plus trans-tracheal injection of adenoviral-mediated p53 versus docetaxel alone in patients with previously treated non-small-cell lung cancer
X. Ning (2011)
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)
Enzymatic MPG DNA repair assays for two different oxidative DNA lesions reveal associations with increased lung cancer risk.
Yael Leitner-Dagan (2014)
Emerging Differences in Epidemiology, Biology, and Therapy
Leno Thomas (2017)
Anàlisi de polimorfismes d’una sola base (SNPs) com a factors predictius de recaiguda en pacients amb càncer de pulmó de cèl•lula no petita quirúrgic
M. C. Guillaumes (2011)
Reviews and comment from the nature publishing group
S. Stephen (2004)
Nucleotide excision repair pathways involved in Cisplatin resistance in non-small-cell lung cancer.
R. Rosell (2003)
Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients.
Q. Shi (2004)
Genotoxicity associated to exposure to Prestige oil during autopsies and cleaning of oil-contaminated birds.
B. Laffon (2006)
Repair Capacity for UV Light–Induced DNA Damage Associated with Risk of Nonmelanoma Skin Cancer and Tumor Progression
Li-e Wang (2007)
Age, sex, and race influence single-strand break repair capacity in a human population.
A. Trzeciak (2008)
Seizure 6-like (SEZ6L) gene and risk for lung cancer.
I. Gorlov (2007)
Heterogeneous tumor features and treatment outcome between males and females with lung cancer (LC): Do gender and sex matter?
S. Frega (2019)
Lung cancer in women: the differences in epidemiology, biology and treatment outcomes
M. Rivera (2009)
A Functional Variant of Tandem Repeats in Human Telomerase Gene Was Associated with Survival of Patients with Early Stages of Non–Small Cell Lung Cancer
L. Wang (2010)
Evidence-Based Clinical Practice Guidelines : ACCP * Epidemiology of Lung Cancer
A. Alberg (2007)
Genome-Wide Sex and Gender Differences in Cancer
Camila M. Lopes-Ramos (2020)
Inter-individual variation in nucleotide excision repair pathway is modulated by non-synonymous polymorphisms in ERCC4 and MBD4 genes.
A. Allione (2013)
A report from the Society for Women's Health Research.
E. Resnick (2005)
Lung cancer: genetics of risk and advances in chemoprevention
R. Keith (2005)
associated with increase lung cancer risk
Ziv Sevilya (2015)See more